Sherry Boschert

SAN FRANCISCO — The investigational drug pegloticase significantly reduced serum urate levels compared with placebo in two randomized, double-blind studies of 212 patients with gout who had previously failed treatment with allopurinol.

Patients received intravenous infusions of placebo or 8 mg pegloticase (Puricase) every 2 or 4 weeks in the 24-week Gout Outcome and Urate Therapy studies (GOUT1 and GOUT2), the results of which were presented by Dr. John S. Sundy at the annual meeting of the American College of Rheumatology.

At baseline, all patients had a serum urate level that was higher than 8 mg/dL (an average of 10 mg/dL) and severe, symptomatic gout, with three or more gout flares in the previous 18 months (an average of 10 flares), one or more tophi (present in 73% of patients), or chronic gouty arthropathy (present in 58% of patients in the studies).

The patient cohort had had gout for a mean of 15 years.

Allopurinol treatment was contraindicated or had failed to reduce serum urate to below 6 mg/dL in these patients.

Treatment in the study was considered successful if a patient's uric acid readings were within the normal range (less than 6 mg/dL) at least 80% of the time in months 3 and 6 of the studies.

None of the patients in the placebo groups of either the 104-patient GOUT1 study or the 108-patient GOUT2 study achieved this goal in the intent-to-treat analysis, according to Dr. Sundy.

However, on a regimen of pegloticase every 2 weeks, 47% of the patients in GOUT1 and 38% of patients in GOUT2 were treated successfully.

On a treatment regimen of pegloticase every 4 weeks, 20% of GOUT1 patients and 48% of GOUT2 patients achieved successful improvements, reported Dr. Sundy, who is a rheumatologist at Duke University, Durham, N.C., and his associates.

The serum urate improvements that were seen with both of the pegloticase regimens were significant compared with placebo, he commented.

Dr. Sundy disclosed that the company that makes pegloticase, Savient Pharmaceuticals, both funded the study and has given research funds or other payments to Dr. Sundy and many of the other investigators on this study, some of whom are Savient employees.

Additionally, Duke University and one of its employees who was not involved in the study hold patents on pegloticase.

A total of eight serious cardiovascular events occurred in patients getting pegloticase: two cardiac arrests, two exacerbations of heart failure leading to death in one patient, two dysrhythmias, one myocardial infection, and one case of angina.

Among other side effects, infusion reactions led to discontinuation of treatment in 11%–13% of patients on pegloticase and none on placebo.

Dr. Sundy said the cardiovascular events “may reflect underlying comorbidity.”

A physician in the audience challenged this assumption, saying the events should occur in the placebo group, too, if that were the case.

A current, ongoing 12-month open-label extension of the study might soon shed some light on this, Dr. Sundy said.

Secondary measures of efficacy in the double-blinded studies found clinically and statistically significant improvements in the pegloticase groups compared with placebo.

Among patients with at least one tophus who were evaluated by computer-assisted photographic analysis, a tophus resolved completely in 21 (40%) of 52 patients getting pegloticase every 2 weeks and 11 (21%) of 52 patients getting pegloticase every 4 weeks, compared with 1 (4%) of 27 patients on placebo.

The number of tender joints decreased by seven in the 2-week pegloticase group and by six in the 4-week group compared with an average decrease of one tender joint on placebo. The number of swollen joints did not differ significantly between groups.

Both pegloticase groups, but not the placebo group, showed significant improvements in the Short Form-36 Health Survey physical component summary score and the physical functioning subscale of the Health Assessment Questionnaire-Disability Index.

The study cohort was 82% male, with a mean age of 55 years and a high degree of comorbidity.

Hypertension was present in 72% of patients, chronic kidney disease in 30%, diabetes in 22%, hypercholesterolemia in 21%, and coronary artery disease in 11% of the patients.

Pegloticase is a recombinant mammalian urate oxidase modified with polyethylene glycol that converts urate to allantoin.

SAN FRANCISCO — The investigational drug pegloticase significantly reduced serum urate levels compared with placebo in two randomized, double-blind studies of 212 patients with gout who had previously failed treatment with allopurinol.

Patients received intravenous infusions of placebo or 8 mg pegloticase (Puricase) every 2 or 4 weeks in the 24-week Gout Outcome and Urate Therapy studies (GOUT1 and GOUT2), the results of which were presented by Dr. John S. Sundy at the annual meeting of the American College of Rheumatology.

At baseline, all patients had a serum urate level that was higher than 8 mg/dL (an average of 10 mg/dL) and severe, symptomatic gout, with three or more gout flares in the previous 18 months (an average of 10 flares), one or more tophi (present in 73% of patients), or chronic gouty arthropathy (present in 58% of patients in the studies).

The patient cohort had had gout for a mean of 15 years.

Allopurinol treatment was contraindicated or had failed to reduce serum urate to below 6 mg/dL in these patients.

Treatment in the study was considered successful if a patient's uric acid readings were within the normal range (less than 6 mg/dL) at least 80% of the time in months 3 and 6 of the studies.

None of the patients in the placebo groups of either the 104-patient GOUT1 study or the 108-patient GOUT2 study achieved this goal in the intent-to-treat analysis, according to Dr. Sundy.

However, on a regimen of pegloticase every 2 weeks, 47% of the patients in GOUT1 and 38% of patients in GOUT2 were treated successfully.

On a treatment regimen of pegloticase every 4 weeks, 20% of GOUT1 patients and 48% of GOUT2 patients achieved successful improvements, reported Dr. Sundy, who is a rheumatologist at Duke University, Durham, N.C., and his associates.

The serum urate improvements that were seen with both of the pegloticase regimens were significant compared with placebo, he commented.

Dr. Sundy disclosed that the company that makes pegloticase, Savient Pharmaceuticals, both funded the study and has given research funds or other payments to Dr. Sundy and many of the other investigators on this study, some of whom are Savient employees.

Additionally, Duke University and one of its employees who was not involved in the study hold patents on pegloticase.

A total of eight serious cardiovascular events occurred in patients getting pegloticase: two cardiac arrests, two exacerbations of heart failure leading to death in one patient, two dysrhythmias, one myocardial infection, and one case of angina.

Among other side effects, infusion reactions led to discontinuation of treatment in 11%–13% of patients on pegloticase and none on placebo.

Dr. Sundy said the cardiovascular events “may reflect underlying comorbidity.”

A physician in the audience challenged this assumption, saying the events should occur in the placebo group, too, if that were the case.

A current, ongoing 12-month open-label extension of the study might soon shed some light on this, Dr. Sundy said.

Secondary measures of efficacy in the double-blinded studies found clinically and statistically significant improvements in the pegloticase groups compared with placebo.

Among patients with at least one tophus who were evaluated by computer-assisted photographic analysis, a tophus resolved completely in 21 (40%) of 52 patients getting pegloticase every 2 weeks and 11 (21%) of 52 patients getting pegloticase every 4 weeks, compared with 1 (4%) of 27 patients on placebo.

The number of tender joints decreased by seven in the 2-week pegloticase group and by six in the 4-week group compared with an average decrease of one tender joint on placebo. The number of swollen joints did not differ significantly between groups.

Both pegloticase groups, but not the placebo group, showed significant improvements in the Short Form-36 Health Survey physical component summary score and the physical functioning subscale of the Health Assessment Questionnaire-Disability Index.

The study cohort was 82% male, with a mean age of 55 years and a high degree of comorbidity.

Hypertension was present in 72% of patients, chronic kidney disease in 30%, diabetes in 22%, hypercholesterolemia in 21%, and coronary artery disease in 11% of the patients.

Pegloticase is a recombinant mammalian urate oxidase modified with polyethylene glycol that converts urate to allantoin.

SAN FRANCISCO — The investigational drug pegloticase significantly reduced serum urate levels compared with placebo in two randomized, double-blind studies of 212 patients with gout who had previously failed treatment with allopurinol.

Patients received intravenous infusions of placebo or 8 mg pegloticase (Puricase) every 2 or 4 weeks in the 24-week Gout Outcome and Urate Therapy studies (GOUT1 and GOUT2), the results of which were presented by Dr. John S. Sundy at the annual meeting of the American College of Rheumatology.

At baseline, all patients had a serum urate level that was higher than 8 mg/dL (an average of 10 mg/dL) and severe, symptomatic gout, with three or more gout flares in the previous 18 months (an average of 10 flares), one or more tophi (present in 73% of patients), or chronic gouty arthropathy (present in 58% of patients in the studies).

The patient cohort had had gout for a mean of 15 years.

Allopurinol treatment was contraindicated or had failed to reduce serum urate to below 6 mg/dL in these patients.

Treatment in the study was considered successful if a patient's uric acid readings were within the normal range (less than 6 mg/dL) at least 80% of the time in months 3 and 6 of the studies.

None of the patients in the placebo groups of either the 104-patient GOUT1 study or the 108-patient GOUT2 study achieved this goal in the intent-to-treat analysis, according to Dr. Sundy.

However, on a regimen of pegloticase every 2 weeks, 47% of the patients in GOUT1 and 38% of patients in GOUT2 were treated successfully.

On a treatment regimen of pegloticase every 4 weeks, 20% of GOUT1 patients and 48% of GOUT2 patients achieved successful improvements, reported Dr. Sundy, who is a rheumatologist at Duke University, Durham, N.C., and his associates.

The serum urate improvements that were seen with both of the pegloticase regimens were significant compared with placebo, he commented.

Dr. Sundy disclosed that the company that makes pegloticase, Savient Pharmaceuticals, both funded the study and has given research funds or other payments to Dr. Sundy and many of the other investigators on this study, some of whom are Savient employees.

Additionally, Duke University and one of its employees who was not involved in the study hold patents on pegloticase.

A total of eight serious cardiovascular events occurred in patients getting pegloticase: two cardiac arrests, two exacerbations of heart failure leading to death in one patient, two dysrhythmias, one myocardial infection, and one case of angina.

Among other side effects, infusion reactions led to discontinuation of treatment in 11%–13% of patients on pegloticase and none on placebo.

Dr. Sundy said the cardiovascular events “may reflect underlying comorbidity.”

A physician in the audience challenged this assumption, saying the events should occur in the placebo group, too, if that were the case.

A current, ongoing 12-month open-label extension of the study might soon shed some light on this, Dr. Sundy said.

Secondary measures of efficacy in the double-blinded studies found clinically and statistically significant improvements in the pegloticase groups compared with placebo.

Among patients with at least one tophus who were evaluated by computer-assisted photographic analysis, a tophus resolved completely in 21 (40%) of 52 patients getting pegloticase every 2 weeks and 11 (21%) of 52 patients getting pegloticase every 4 weeks, compared with 1 (4%) of 27 patients on placebo.

The number of tender joints decreased by seven in the 2-week pegloticase group and by six in the 4-week group compared with an average decrease of one tender joint on placebo. The number of swollen joints did not differ significantly between groups.

Both pegloticase groups, but not the placebo group, showed significant improvements in the Short Form-36 Health Survey physical component summary score and the physical functioning subscale of the Health Assessment Questionnaire-Disability Index.

The study cohort was 82% male, with a mean age of 55 years and a high degree of comorbidity.

Hypertension was present in 72% of patients, chronic kidney disease in 30%, diabetes in 22%, hypercholesterolemia in 21%, and coronary artery disease in 11% of the patients.

Pegloticase is a recombinant mammalian urate oxidase modified with polyethylene glycol that converts urate to allantoin.

SAN FRANCISCO — Dual-energy computed tomography scans showed red-colored uric acid deposits in 20 consecutive patients with clinically obvious tophaceous gout but not in 10 controls with other nongout joint conditions.

The 100% sensitivity and specificity of dual-energy computed tomography (DECT) to identify uric acid deposits could provide a needed imaging tool to aid in gout diagnosis and treatment, Dr. Abdullatif M. Alarfaj said at the annual meeting of the American College of Rheumatology.

DECT assesses chemical composition and provides specific color-coded displays to differentiate between uric acid (which shows red), calcium (blue), and other renal calculi, previous investigators have shown.

The current proof-of-concept study, in addition to assessing the accuracy of DECT in gout patients, also measured the uric acid burden in peripheral joints and performed a computerized quantification of tophus volume. The volume of uric acid in each anatomic area was measured by automated volume estimation software. The sum of tophus volume in the hands, wrists, elbows, feet, ankles, and knees comprised the total uric acid volume of peripheral joints.

DECT scans identified 440 areas of urate deposition, compared with 111 areas identified on clinical examination, reported Dr. Alarfaj of the University of British Columbia, Vancouver, and his associates. The investigators have no conflicts of interest related to this study.

DECT could be used to detect subclinical tophus deposits and the extent of intra- and extra-articular gout, he said, adding it could be used to measure individual tophus volume and total burden.

The relatively new technology also may be used in evaluating nodular lesions, diagnosing concurrent gout in patients with other arthropathies, and identifying urate deposits in body areas atypical for gout. An individual DECT scan can cost about one-sixth of the amount for an MRI, Dr. Alarfaj's senior investigator, Dr. Hyon Choi, said. The DECT hardware equipment is very expensive but is used for a variety of purposes, such as imaging coronary artery calcifications and renal calculi. The technology provides dramatic color displays and can be used to create impressive three-dimensional images of uric acid deposits that could aid clinicians in communicating about the disease to patients with gout, he added. The patients in the gout group had an average 12-year history of gout and nine painful joints in the previous year. Mean serum uric acid level was 492 micromol/L; mean age was 63; 75% were male; and 12 were white. Comorbidities were present in 17 patients.

SAN FRANCISCO — Dual-energy computed tomography scans showed red-colored uric acid deposits in 20 consecutive patients with clinically obvious tophaceous gout but not in 10 controls with other nongout joint conditions.

The 100% sensitivity and specificity of dual-energy computed tomography (DECT) to identify uric acid deposits could provide a needed imaging tool to aid in gout diagnosis and treatment, Dr. Abdullatif M. Alarfaj said at the annual meeting of the American College of Rheumatology.

DECT assesses chemical composition and provides specific color-coded displays to differentiate between uric acid (which shows red), calcium (blue), and other renal calculi, previous investigators have shown.

The current proof-of-concept study, in addition to assessing the accuracy of DECT in gout patients, also measured the uric acid burden in peripheral joints and performed a computerized quantification of tophus volume. The volume of uric acid in each anatomic area was measured by automated volume estimation software. The sum of tophus volume in the hands, wrists, elbows, feet, ankles, and knees comprised the total uric acid volume of peripheral joints.

DECT scans identified 440 areas of urate deposition, compared with 111 areas identified on clinical examination, reported Dr. Alarfaj of the University of British Columbia, Vancouver, and his associates. The investigators have no conflicts of interest related to this study.

DECT could be used to detect subclinical tophus deposits and the extent of intra- and extra-articular gout, he said, adding it could be used to measure individual tophus volume and total burden.

The relatively new technology also may be used in evaluating nodular lesions, diagnosing concurrent gout in patients with other arthropathies, and identifying urate deposits in body areas atypical for gout. An individual DECT scan can cost about one-sixth of the amount for an MRI, Dr. Alarfaj's senior investigator, Dr. Hyon Choi, said. The DECT hardware equipment is very expensive but is used for a variety of purposes, such as imaging coronary artery calcifications and renal calculi. The technology provides dramatic color displays and can be used to create impressive three-dimensional images of uric acid deposits that could aid clinicians in communicating about the disease to patients with gout, he added. The patients in the gout group had an average 12-year history of gout and nine painful joints in the previous year. Mean serum uric acid level was 492 micromol/L; mean age was 63; 75% were male; and 12 were white. Comorbidities were present in 17 patients.

SAN FRANCISCO — Dual-energy computed tomography scans showed red-colored uric acid deposits in 20 consecutive patients with clinically obvious tophaceous gout but not in 10 controls with other nongout joint conditions.

The 100% sensitivity and specificity of dual-energy computed tomography (DECT) to identify uric acid deposits could provide a needed imaging tool to aid in gout diagnosis and treatment, Dr. Abdullatif M. Alarfaj said at the annual meeting of the American College of Rheumatology.

DECT assesses chemical composition and provides specific color-coded displays to differentiate between uric acid (which shows red), calcium (blue), and other renal calculi, previous investigators have shown.

The current proof-of-concept study, in addition to assessing the accuracy of DECT in gout patients, also measured the uric acid burden in peripheral joints and performed a computerized quantification of tophus volume. The volume of uric acid in each anatomic area was measured by automated volume estimation software. The sum of tophus volume in the hands, wrists, elbows, feet, ankles, and knees comprised the total uric acid volume of peripheral joints.

DECT scans identified 440 areas of urate deposition, compared with 111 areas identified on clinical examination, reported Dr. Alarfaj of the University of British Columbia, Vancouver, and his associates. The investigators have no conflicts of interest related to this study.

DECT could be used to detect subclinical tophus deposits and the extent of intra- and extra-articular gout, he said, adding it could be used to measure individual tophus volume and total burden.

The relatively new technology also may be used in evaluating nodular lesions, diagnosing concurrent gout in patients with other arthropathies, and identifying urate deposits in body areas atypical for gout. An individual DECT scan can cost about one-sixth of the amount for an MRI, Dr. Alarfaj's senior investigator, Dr. Hyon Choi, said. The DECT hardware equipment is very expensive but is used for a variety of purposes, such as imaging coronary artery calcifications and renal calculi. The technology provides dramatic color displays and can be used to create impressive three-dimensional images of uric acid deposits that could aid clinicians in communicating about the disease to patients with gout, he added. The patients in the gout group had an average 12-year history of gout and nine painful joints in the previous year. Mean serum uric acid level was 492 micromol/L; mean age was 63; 75% were male; and 12 were white. Comorbidities were present in 17 patients.

STANFORD, CALIF. — A teenage patient complains of “heavy” menstrual periods. Her mother mentions that her daughter never gets periods during soccer season.

Should you evaluate the girl for abnormal uterine bleeding?

Test your knowledge of what's normal or abnormal for teenage menstruation by taking the true or false quiz (see box) before reading commentary provided by Dr. Paula J. Hillard at a pediatric update sponsored by Stanford University.

Puberty and menarche generally arrive several months earlier for African American girls than for white girls, studies in the past decade have shown. While only 7% of white girls had “early” breast development or pubic hair by age 7 years, this occurred in 27% of African American girls, one study found (Pediatrics 1997;99:505–12).

Guidelines suggest not evaluating for precocious puberty unless breast development or pubic hair occurs before age 7 years in white girls or before age 6 years in African American girls. If there are other signs or symptoms such as severe headache or neurologic symptoms, however, an evaluation is in order, said Dr. Hillard, professor of obstetrics and gynecology at the university.

The age at which girls start their periods has been declining since 1800. Declines in the age of menarche up until the 1960s resulted from positive changes such as better nutrition and less infectious disease. Since then, however, declines in the age of menarche seem to be related to negative changes such as overeating and limited physical activity.

Over the past 20 years, the age of menarche declined by 2 months in white girls and by more than 9 months in African American girls. Federal data in 1999–2002 showed the average age of menarche to be 12.5 years in whites and 12.1 years in non-Hispanic blacks and Mexican Americans (J. Pediatr. 2005;147:753–60). The duration of menstrual bleeding has held steady, lasting 2–7 days per period in 92% of teen girls. “Early” or “late” menarche can be defined as 2.5 standard deviations from the mean (ages 9 or 15 years for white girls), said Dr. Hillard, who did not have similar data for African American girls.

An evaluation would be appropriate if a girl has no menses by age 15 years. An evaluation also is warranted if there's no breast development by age 13 years, if menses haven't started 2.5–3 years after breast development, if there are signs or symptoms of pregnancy, or if the patient is 14 years old with obesity, acne, and hirsutism.

Consider polycystic ovarian syndrome (PCOS), anorexia nervosa, or other eating disorders as possible causes. If the mother says her daughter never gets periods during soccer season, “this may be cause for concern,” Dr. Hillard said.

Early menstrual cycles in a girl's life may be anovulatory and shorter or longer than some others; they should not be chaotically irregular.

Most cycles average 21–45 days in the first gynecologic year and trend toward shorter, more regular cycles with age. A 90-day cycle still falls within the 95th percentile during the first year of menarche. Beyond 90 days, evaluate for PCOS, eating disorders, thyroid disease, hyperprolactinemia, gonadal dysgenesis, or premature ovarian failure.

The True or FalseMenstruation Quiz

The age of puberty has been declining.

Pubertal development at about age 8 years constitutes precocious puberty.

Girls begin menstruating at an average age of 13 years.

The age of menarche has been declining.

Normal menstrual periods last 2–7 days.

A girl who has not started menstruating by age 15 years should be evaluated.

In the first year of menses, it's normal to have chaotically irregular cycles.

Menstruation typically cycles every 21–45 days, but a 90-day cycle also is normal.

Quiz Answers: 1. True 2. False 3. False 4. True 5. True 6. True 7. False 8. True

STANFORD, CALIF. — A teenage patient complains of “heavy” menstrual periods. Her mother mentions that her daughter never gets periods during soccer season.

Should you evaluate the girl for abnormal uterine bleeding?

Test your knowledge of what's normal or abnormal for teenage menstruation by taking the true or false quiz (see box) before reading commentary provided by Dr. Paula J. Hillard at a pediatric update sponsored by Stanford University.

Puberty and menarche generally arrive several months earlier for African American girls than for white girls, studies in the past decade have shown. While only 7% of white girls had “early” breast development or pubic hair by age 7 years, this occurred in 27% of African American girls, one study found (Pediatrics 1997;99:505–12).

Guidelines suggest not evaluating for precocious puberty unless breast development or pubic hair occurs before age 7 years in white girls or before age 6 years in African American girls. If there are other signs or symptoms such as severe headache or neurologic symptoms, however, an evaluation is in order, said Dr. Hillard, professor of obstetrics and gynecology at the university.

The age at which girls start their periods has been declining since 1800. Declines in the age of menarche up until the 1960s resulted from positive changes such as better nutrition and less infectious disease. Since then, however, declines in the age of menarche seem to be related to negative changes such as overeating and limited physical activity.

Over the past 20 years, the age of menarche declined by 2 months in white girls and by more than 9 months in African American girls. Federal data in 1999–2002 showed the average age of menarche to be 12.5 years in whites and 12.1 years in non-Hispanic blacks and Mexican Americans (J. Pediatr. 2005;147:753–60). The duration of menstrual bleeding has held steady, lasting 2–7 days per period in 92% of teen girls. “Early” or “late” menarche can be defined as 2.5 standard deviations from the mean (ages 9 or 15 years for white girls), said Dr. Hillard, who did not have similar data for African American girls.

An evaluation would be appropriate if a girl has no menses by age 15 years. An evaluation also is warranted if there's no breast development by age 13 years, if menses haven't started 2.5–3 years after breast development, if there are signs or symptoms of pregnancy, or if the patient is 14 years old with obesity, acne, and hirsutism.

Consider polycystic ovarian syndrome (PCOS), anorexia nervosa, or other eating disorders as possible causes. If the mother says her daughter never gets periods during soccer season, “this may be cause for concern,” Dr. Hillard said.

Early menstrual cycles in a girl's life may be anovulatory and shorter or longer than some others; they should not be chaotically irregular.

Most cycles average 21–45 days in the first gynecologic year and trend toward shorter, more regular cycles with age. A 90-day cycle still falls within the 95th percentile during the first year of menarche. Beyond 90 days, evaluate for PCOS, eating disorders, thyroid disease, hyperprolactinemia, gonadal dysgenesis, or premature ovarian failure.

The True or FalseMenstruation Quiz

The age of puberty has been declining.

Pubertal development at about age 8 years constitutes precocious puberty.

Girls begin menstruating at an average age of 13 years.

The age of menarche has been declining.

Normal menstrual periods last 2–7 days.

A girl who has not started menstruating by age 15 years should be evaluated.

In the first year of menses, it's normal to have chaotically irregular cycles.

Menstruation typically cycles every 21–45 days, but a 90-day cycle also is normal.

Quiz Answers: 1. True 2. False 3. False 4. True 5. True 6. True 7. False 8. True

STANFORD, CALIF. — A teenage patient complains of “heavy” menstrual periods. Her mother mentions that her daughter never gets periods during soccer season.

Should you evaluate the girl for abnormal uterine bleeding?

Test your knowledge of what's normal or abnormal for teenage menstruation by taking the true or false quiz (see box) before reading commentary provided by Dr. Paula J. Hillard at a pediatric update sponsored by Stanford University.

Puberty and menarche generally arrive several months earlier for African American girls than for white girls, studies in the past decade have shown. While only 7% of white girls had “early” breast development or pubic hair by age 7 years, this occurred in 27% of African American girls, one study found (Pediatrics 1997;99:505–12).

Guidelines suggest not evaluating for precocious puberty unless breast development or pubic hair occurs before age 7 years in white girls or before age 6 years in African American girls. If there are other signs or symptoms such as severe headache or neurologic symptoms, however, an evaluation is in order, said Dr. Hillard, professor of obstetrics and gynecology at the university.

The age at which girls start their periods has been declining since 1800. Declines in the age of menarche up until the 1960s resulted from positive changes such as better nutrition and less infectious disease. Since then, however, declines in the age of menarche seem to be related to negative changes such as overeating and limited physical activity.

Over the past 20 years, the age of menarche declined by 2 months in white girls and by more than 9 months in African American girls. Federal data in 1999–2002 showed the average age of menarche to be 12.5 years in whites and 12.1 years in non-Hispanic blacks and Mexican Americans (J. Pediatr. 2005;147:753–60). The duration of menstrual bleeding has held steady, lasting 2–7 days per period in 92% of teen girls. “Early” or “late” menarche can be defined as 2.5 standard deviations from the mean (ages 9 or 15 years for white girls), said Dr. Hillard, who did not have similar data for African American girls.

An evaluation would be appropriate if a girl has no menses by age 15 years. An evaluation also is warranted if there's no breast development by age 13 years, if menses haven't started 2.5–3 years after breast development, if there are signs or symptoms of pregnancy, or if the patient is 14 years old with obesity, acne, and hirsutism.

Consider polycystic ovarian syndrome (PCOS), anorexia nervosa, or other eating disorders as possible causes. If the mother says her daughter never gets periods during soccer season, “this may be cause for concern,” Dr. Hillard said.

Early menstrual cycles in a girl's life may be anovulatory and shorter or longer than some others; they should not be chaotically irregular.

Most cycles average 21–45 days in the first gynecologic year and trend toward shorter, more regular cycles with age. A 90-day cycle still falls within the 95th percentile during the first year of menarche. Beyond 90 days, evaluate for PCOS, eating disorders, thyroid disease, hyperprolactinemia, gonadal dysgenesis, or premature ovarian failure.

The True or FalseMenstruation Quiz

The age of puberty has been declining.

Pubertal development at about age 8 years constitutes precocious puberty.

Girls begin menstruating at an average age of 13 years.

The age of menarche has been declining.

Normal menstrual periods last 2–7 days.

A girl who has not started menstruating by age 15 years should be evaluated.

In the first year of menses, it's normal to have chaotically irregular cycles.

Menstruation typically cycles every 21–45 days, but a 90-day cycle also is normal.

Quiz Answers: 1. True 2. False 3. False 4. True 5. True 6. True 7. False 8. True

SAN FRANCISCO — Remote review of digital immunohistochemistry slides by pathologists seemed to be as accurate as in-person evaluations by light microscopy for diagnosis of dysplastic nevi, but was less successful for diagnosing early malignant melanoma.

Three pathologists viewed 55–60 cases of dysplastic nevi with varying atypia and early melanomas on hematoxylin and eosin- and immunohistochemical-stained slides via telepathology. A remote site hosted the digital slides, and the consulting pathologists evaluated them via a Java-enabled Web browser. The pathologists also evaluated a glass set of slides for the cases.

Preliminary results showed that there was a high concordance rate between digital and light microscopic diagnoses for dysplastic nevi, but a few diagnostic discrepancies were seen between telepathology and microscopy when early malignant melanomas were evaluated, Dr. Jill Buckthal-McCuin of the University of Pittsburgh reported in a poster that was presented at the annual meeting of the American Society of Dermatopathology.

Evaluations by telepathology took more than twice as long to perform as microscopy evaluations, mainly because focusing was slow during telepathology. If the time spent on shipping the glass slides for microscopic evaluation were included, however, telepathology was faster, Dr. Buckthal-McCuin added.

An individual evaluator's level of experience in dermatopathology and experience with telepathology may have been a factor in diagnostic accuracy, she suggested.

A dermatopathology fellow made the correct diagnosis in 21 (36%) of 59 cases evaluated with digital telepathology. A staff dermatologist with 1 year of experience was correct in 19 (45%) of 42 diagnoses via telepathology, and said he was not comfortable evaluating 18 other cases, including 8 cases of suspected melanoma.

An attending dermatopathologist with more than 5 years' experience was correct in 23 (42%) of 55 diagnoses via telepathology.

Each of the evaluators misgraded some dysplastic nevi by one degree, which would not affect decisions regarding treatment.

Overall, the diagnoses that were made via telepathology would have resulted in correct treatment in 90% of the cases evaluated by the fellow, 76% of cases that the junior attending dermatopathologist agreed to evaluate, and 67% of the cases reviewed by the senior attending dermatopathologist.

Increasing demands are being placed on pathologists, and in some settings a trained pathologist in a specific subspecialty is not available on site, Dr. Buckthal-McCuin noted.

Digital telepathology might contribute to the more efficient use of pathologists by allowing real-time review of remote cases, delayed image review, subspecialty reviews, and second opinions in a timely fashion, but more study is needed to confirm the utility of this diagnostic method, she said.

The three pathologists in the study reported not feeling comfortable when the slide was moved at the remote site, because an area of interest often was omitted or out of focus. They agreed that the robotic microscope provided excellent detail and would be useful in nonprimary diagnosis.

The fellow complained that the inability to evaluate the immunohistochemical and hematoxylin and eosin slides together hampered the remote diagnosis by telepathology.

Dr. Buckthal-McCuin and her associates plan to study telepathology evaluation of hematoxylin and eosin and immunohistochemical slides together, and said that they expect the degree of concordance with glass-based evaluation to be similar to the findings in this preliminary study.

SAN FRANCISCO — Remote review of digital immunohistochemistry slides by pathologists seemed to be as accurate as in-person evaluations by light microscopy for diagnosis of dysplastic nevi, but was less successful for diagnosing early malignant melanoma.

Three pathologists viewed 55–60 cases of dysplastic nevi with varying atypia and early melanomas on hematoxylin and eosin- and immunohistochemical-stained slides via telepathology. A remote site hosted the digital slides, and the consulting pathologists evaluated them via a Java-enabled Web browser. The pathologists also evaluated a glass set of slides for the cases.

Preliminary results showed that there was a high concordance rate between digital and light microscopic diagnoses for dysplastic nevi, but a few diagnostic discrepancies were seen between telepathology and microscopy when early malignant melanomas were evaluated, Dr. Jill Buckthal-McCuin of the University of Pittsburgh reported in a poster that was presented at the annual meeting of the American Society of Dermatopathology.

Evaluations by telepathology took more than twice as long to perform as microscopy evaluations, mainly because focusing was slow during telepathology. If the time spent on shipping the glass slides for microscopic evaluation were included, however, telepathology was faster, Dr. Buckthal-McCuin added.

An individual evaluator's level of experience in dermatopathology and experience with telepathology may have been a factor in diagnostic accuracy, she suggested.

A dermatopathology fellow made the correct diagnosis in 21 (36%) of 59 cases evaluated with digital telepathology. A staff dermatologist with 1 year of experience was correct in 19 (45%) of 42 diagnoses via telepathology, and said he was not comfortable evaluating 18 other cases, including 8 cases of suspected melanoma.

An attending dermatopathologist with more than 5 years' experience was correct in 23 (42%) of 55 diagnoses via telepathology.

Each of the evaluators misgraded some dysplastic nevi by one degree, which would not affect decisions regarding treatment.

Overall, the diagnoses that were made via telepathology would have resulted in correct treatment in 90% of the cases evaluated by the fellow, 76% of cases that the junior attending dermatopathologist agreed to evaluate, and 67% of the cases reviewed by the senior attending dermatopathologist.

Increasing demands are being placed on pathologists, and in some settings a trained pathologist in a specific subspecialty is not available on site, Dr. Buckthal-McCuin noted.

Digital telepathology might contribute to the more efficient use of pathologists by allowing real-time review of remote cases, delayed image review, subspecialty reviews, and second opinions in a timely fashion, but more study is needed to confirm the utility of this diagnostic method, she said.

The three pathologists in the study reported not feeling comfortable when the slide was moved at the remote site, because an area of interest often was omitted or out of focus. They agreed that the robotic microscope provided excellent detail and would be useful in nonprimary diagnosis.

The fellow complained that the inability to evaluate the immunohistochemical and hematoxylin and eosin slides together hampered the remote diagnosis by telepathology.

Dr. Buckthal-McCuin and her associates plan to study telepathology evaluation of hematoxylin and eosin and immunohistochemical slides together, and said that they expect the degree of concordance with glass-based evaluation to be similar to the findings in this preliminary study.

SAN FRANCISCO — Remote review of digital immunohistochemistry slides by pathologists seemed to be as accurate as in-person evaluations by light microscopy for diagnosis of dysplastic nevi, but was less successful for diagnosing early malignant melanoma.

Three pathologists viewed 55–60 cases of dysplastic nevi with varying atypia and early melanomas on hematoxylin and eosin- and immunohistochemical-stained slides via telepathology. A remote site hosted the digital slides, and the consulting pathologists evaluated them via a Java-enabled Web browser. The pathologists also evaluated a glass set of slides for the cases.

Preliminary results showed that there was a high concordance rate between digital and light microscopic diagnoses for dysplastic nevi, but a few diagnostic discrepancies were seen between telepathology and microscopy when early malignant melanomas were evaluated, Dr. Jill Buckthal-McCuin of the University of Pittsburgh reported in a poster that was presented at the annual meeting of the American Society of Dermatopathology.

Evaluations by telepathology took more than twice as long to perform as microscopy evaluations, mainly because focusing was slow during telepathology. If the time spent on shipping the glass slides for microscopic evaluation were included, however, telepathology was faster, Dr. Buckthal-McCuin added.

An individual evaluator's level of experience in dermatopathology and experience with telepathology may have been a factor in diagnostic accuracy, she suggested.

A dermatopathology fellow made the correct diagnosis in 21 (36%) of 59 cases evaluated with digital telepathology. A staff dermatologist with 1 year of experience was correct in 19 (45%) of 42 diagnoses via telepathology, and said he was not comfortable evaluating 18 other cases, including 8 cases of suspected melanoma.

An attending dermatopathologist with more than 5 years' experience was correct in 23 (42%) of 55 diagnoses via telepathology.

Each of the evaluators misgraded some dysplastic nevi by one degree, which would not affect decisions regarding treatment.

Overall, the diagnoses that were made via telepathology would have resulted in correct treatment in 90% of the cases evaluated by the fellow, 76% of cases that the junior attending dermatopathologist agreed to evaluate, and 67% of the cases reviewed by the senior attending dermatopathologist.

Increasing demands are being placed on pathologists, and in some settings a trained pathologist in a specific subspecialty is not available on site, Dr. Buckthal-McCuin noted.

Digital telepathology might contribute to the more efficient use of pathologists by allowing real-time review of remote cases, delayed image review, subspecialty reviews, and second opinions in a timely fashion, but more study is needed to confirm the utility of this diagnostic method, she said.

The three pathologists in the study reported not feeling comfortable when the slide was moved at the remote site, because an area of interest often was omitted or out of focus. They agreed that the robotic microscope provided excellent detail and would be useful in nonprimary diagnosis.

The fellow complained that the inability to evaluate the immunohistochemical and hematoxylin and eosin slides together hampered the remote diagnosis by telepathology.

Dr. Buckthal-McCuin and her associates plan to study telepathology evaluation of hematoxylin and eosin and immunohistochemical slides together, and said that they expect the degree of concordance with glass-based evaluation to be similar to the findings in this preliminary study.

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

SAN FRANCISCO — The gentle martial art tai chi significantly improved pain and physical function in a randomized, controlled trial in 40 patients with knee osteoarthritis.

Participants were randomly selected to attend hour-long classes twice a week for 12 weeks to learn and practice 10 modified forms of classical Yang style tai chi or to receive wellness education and engage in stretching in a control group. Patient characteristics were similar between groups, with baseline pain scores of 209 in the tai chi group and 220 in the control group on the Western Ontario and McMaster Osteoarthritis (WOMAC) Index, which was the main outcome measure.

After 12 weeks, WOMAC pain scores decreased by 157 points in the tai chi group and 39 points in the control group, a significant difference between groups (P = .004), Dr. Chenchen Wang reported at the annual meeting of the American College of Rheumatology.

She and her associates repeated the pain assessment at 24 and 48 weeks to gauge the durability of the effects. Although the WOMAC pain scores remained significantly different between groups at 24 weeks, they did not at 48 weeks as some patients stopped practicing tai chi once the 12-week intervention had ended. Those who continued their tai chi practice, however, continued to show significant improvements in pain and secondary measures of function, compared with the control group, added Dr. Wang of Tufts University, Boston.

The tai chi group showed significant improvements, compared with the control group, in the WOMAC physical function score; the patient and physician global assessment scores (on visual analog scales); a timed chair-stand test; an assessment of knee proprioception; and in depression scores on the Center for Epidemiology Studies Depression (CES-D) Index.

“This is a very promising study,” Dr. Wang said. “However, these results should be confirmed by future large studies.”

Tai chi is an ancient Chinese exercise that combines meditation with slow, gentle, graceful movements; deep breathing; and relaxation. It uses an integrated mind-body approach to enhance muscle function, balance, and flexibility. Findings from a previous review by Dr. Wang and her associates of 47 studies of tai chi for various chronic medical problems suggested benefits in physical and mental health and function (Arch. Intern. Med.2004;164:493-501), but a dearth of high-quality studies left these conclusions in doubt and led to the current study, she said.

Sessions in the current trial included a warm-up, review of technique, and practice of the meditative movements, some of which were modified for the osteoarthritic cohort by incorporating chairs or other accommodations. The mind-body interaction of tai chi makes it difficult to compare it to a sham intervention, so the investigators used a control of conventional stretching and education about osteoarthritis, diet, nutrition, and more.

The patients were obese, with a baseline body mass index of 30 kg/m

Some patients used nonsteroidal anti-inflammatory drugs or other analgesics during the study, but medication use did not differ significantly between groups.

Pain scores decreased 157 points after 12 weeks of tai chi, compared with a 39-point decrease in the control group. ©Anne

SAN FRANCISCO — The gentle martial art tai chi significantly improved pain and physical function in a randomized, controlled trial in 40 patients with knee osteoarthritis.

Participants were randomly selected to attend hour-long classes twice a week for 12 weeks to learn and practice 10 modified forms of classical Yang style tai chi or to receive wellness education and engage in stretching in a control group. Patient characteristics were similar between groups, with baseline pain scores of 209 in the tai chi group and 220 in the control group on the Western Ontario and McMaster Osteoarthritis (WOMAC) Index, which was the main outcome measure.

After 12 weeks, WOMAC pain scores decreased by 157 points in the tai chi group and 39 points in the control group, a significant difference between groups (P = .004), Dr. Chenchen Wang reported at the annual meeting of the American College of Rheumatology.

She and her associates repeated the pain assessment at 24 and 48 weeks to gauge the durability of the effects. Although the WOMAC pain scores remained significantly different between groups at 24 weeks, they did not at 48 weeks as some patients stopped practicing tai chi once the 12-week intervention had ended. Those who continued their tai chi practice, however, continued to show significant improvements in pain and secondary measures of function, compared with the control group, added Dr. Wang of Tufts University, Boston.

The tai chi group showed significant improvements, compared with the control group, in the WOMAC physical function score; the patient and physician global assessment scores (on visual analog scales); a timed chair-stand test; an assessment of knee proprioception; and in depression scores on the Center for Epidemiology Studies Depression (CES-D) Index.

“This is a very promising study,” Dr. Wang said. “However, these results should be confirmed by future large studies.”

Tai chi is an ancient Chinese exercise that combines meditation with slow, gentle, graceful movements; deep breathing; and relaxation. It uses an integrated mind-body approach to enhance muscle function, balance, and flexibility. Findings from a previous review by Dr. Wang and her associates of 47 studies of tai chi for various chronic medical problems suggested benefits in physical and mental health and function (Arch. Intern. Med.2004;164:493-501), but a dearth of high-quality studies left these conclusions in doubt and led to the current study, she said.

Sessions in the current trial included a warm-up, review of technique, and practice of the meditative movements, some of which were modified for the osteoarthritic cohort by incorporating chairs or other accommodations. The mind-body interaction of tai chi makes it difficult to compare it to a sham intervention, so the investigators used a control of conventional stretching and education about osteoarthritis, diet, nutrition, and more.

The patients were obese, with a baseline body mass index of 30 kg/m

Some patients used nonsteroidal anti-inflammatory drugs or other analgesics during the study, but medication use did not differ significantly between groups.

Pain scores decreased 157 points after 12 weeks of tai chi, compared with a 39-point decrease in the control group. ©Anne

SAN FRANCISCO — The gentle martial art tai chi significantly improved pain and physical function in a randomized, controlled trial in 40 patients with knee osteoarthritis.

Participants were randomly selected to attend hour-long classes twice a week for 12 weeks to learn and practice 10 modified forms of classical Yang style tai chi or to receive wellness education and engage in stretching in a control group. Patient characteristics were similar between groups, with baseline pain scores of 209 in the tai chi group and 220 in the control group on the Western Ontario and McMaster Osteoarthritis (WOMAC) Index, which was the main outcome measure.

After 12 weeks, WOMAC pain scores decreased by 157 points in the tai chi group and 39 points in the control group, a significant difference between groups (P = .004), Dr. Chenchen Wang reported at the annual meeting of the American College of Rheumatology.

She and her associates repeated the pain assessment at 24 and 48 weeks to gauge the durability of the effects. Although the WOMAC pain scores remained significantly different between groups at 24 weeks, they did not at 48 weeks as some patients stopped practicing tai chi once the 12-week intervention had ended. Those who continued their tai chi practice, however, continued to show significant improvements in pain and secondary measures of function, compared with the control group, added Dr. Wang of Tufts University, Boston.

The tai chi group showed significant improvements, compared with the control group, in the WOMAC physical function score; the patient and physician global assessment scores (on visual analog scales); a timed chair-stand test; an assessment of knee proprioception; and in depression scores on the Center for Epidemiology Studies Depression (CES-D) Index.

“This is a very promising study,” Dr. Wang said. “However, these results should be confirmed by future large studies.”

Tai chi is an ancient Chinese exercise that combines meditation with slow, gentle, graceful movements; deep breathing; and relaxation. It uses an integrated mind-body approach to enhance muscle function, balance, and flexibility. Findings from a previous review by Dr. Wang and her associates of 47 studies of tai chi for various chronic medical problems suggested benefits in physical and mental health and function (Arch. Intern. Med.2004;164:493-501), but a dearth of high-quality studies left these conclusions in doubt and led to the current study, she said.

Sessions in the current trial included a warm-up, review of technique, and practice of the meditative movements, some of which were modified for the osteoarthritic cohort by incorporating chairs or other accommodations. The mind-body interaction of tai chi makes it difficult to compare it to a sham intervention, so the investigators used a control of conventional stretching and education about osteoarthritis, diet, nutrition, and more.

The patients were obese, with a baseline body mass index of 30 kg/m

Some patients used nonsteroidal anti-inflammatory drugs or other analgesics during the study, but medication use did not differ significantly between groups.

Pain scores decreased 157 points after 12 weeks of tai chi, compared with a 39-point decrease in the control group. ©Anne

Diagnosis: Verruciform Xanthoma

SAN FRANCISCO — Physicians performed several biopsies of the noncrusting, nonulcerating plaque over a period of several months, looking for possible squamous cell carcinoma. Results were negative for cancer but did show epidermal acanthosis.

This and other characteristics seen on histology identified the plaque as verruciform xanthoma, an uncommon and usually benign entity that has been associated with recessive dystrophic epidermolysis bullosa in only three previous case reports, Dr. Kathie Huang reported at the annual meeting of the Pacific Dermatologic Association.

Verruciform xanthoma can mimic squamous cell carcinoma and warrants a biopsy for evaluation.

Atypia and carcinoma can arise within verruciform xanthoma, according to rare case reports, so it requires close follow-up, said Dr. Huang of Stanford (Calif.) University.

One previous report recommended surgical excision of the lesion to avoid any remote risk of carcinoma, and others called for close follow-up.

In the current case, low-power magnification revealed epidermal acanthosis, papillomatosis, and hyperkeratosis.

On closer inspection, pathologists could see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells filling the papillary dermis. Higher magnification showed clear foamy xanthoma cells in the papillary dermis.

The boy's verruciform xanthoma lesion was surrounded by a difficult-to-heal wound. Recessive dystrophic epidermolysis bullosa is characterized by skin fragility, recurrent trauma, and impaired wound healing.

During trials of treatment with imiquimod, topical antibiotics, and a topical steroid, the verruciform xanthoma plaque maintained its color and quality, and increased some in size before stabilizing.

Dr. Huang and the attending physician, Dr. Anna Bruckner of the university, said they feared that excision of the lesion would increase morbidity by resulting in a nonhealing wound because of the patient's recessive dystrophic epidermolysis bullosa and malnutrition. They opted to manage with close follow-up.

The patient now is 14 years old and doing well, Dr. Huang reported. The verruciform xanthoma plaque has not changed significantly, and has no ulceration or crusting.

In general, verruciform xanthoma usually is found in the oral mucosa, but also has been seen in the anogenital area and other sites. It also can arise in special settings, such as in patients with chronic lymphedema on the legs, recessive dystrophic epidermolysis bullosa, or other conditions.

The etiology is poorly understood. Trauma, irritation, and infection are thought to be contributors to verruciform xanthoma.

One case report associated the disease with human papillomavirus (HPV) infection, but several subsequent case series found no association with HPV, "so it's currently thought not to be related" to HPV, she said.

Pathologists were able to see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells in the papillary dermis (at high magnification). Courtesy Dr. Kathie Huang

Diagnosis: Verruciform Xanthoma

SAN FRANCISCO — Physicians performed several biopsies of the noncrusting, nonulcerating plaque over a period of several months, looking for possible squamous cell carcinoma. Results were negative for cancer but did show epidermal acanthosis.

This and other characteristics seen on histology identified the plaque as verruciform xanthoma, an uncommon and usually benign entity that has been associated with recessive dystrophic epidermolysis bullosa in only three previous case reports, Dr. Kathie Huang reported at the annual meeting of the Pacific Dermatologic Association.

Verruciform xanthoma can mimic squamous cell carcinoma and warrants a biopsy for evaluation.

Atypia and carcinoma can arise within verruciform xanthoma, according to rare case reports, so it requires close follow-up, said Dr. Huang of Stanford (Calif.) University.

One previous report recommended surgical excision of the lesion to avoid any remote risk of carcinoma, and others called for close follow-up.

In the current case, low-power magnification revealed epidermal acanthosis, papillomatosis, and hyperkeratosis.

On closer inspection, pathologists could see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells filling the papillary dermis. Higher magnification showed clear foamy xanthoma cells in the papillary dermis.

The boy's verruciform xanthoma lesion was surrounded by a difficult-to-heal wound. Recessive dystrophic epidermolysis bullosa is characterized by skin fragility, recurrent trauma, and impaired wound healing.

During trials of treatment with imiquimod, topical antibiotics, and a topical steroid, the verruciform xanthoma plaque maintained its color and quality, and increased some in size before stabilizing.

Dr. Huang and the attending physician, Dr. Anna Bruckner of the university, said they feared that excision of the lesion would increase morbidity by resulting in a nonhealing wound because of the patient's recessive dystrophic epidermolysis bullosa and malnutrition. They opted to manage with close follow-up.

The patient now is 14 years old and doing well, Dr. Huang reported. The verruciform xanthoma plaque has not changed significantly, and has no ulceration or crusting.

In general, verruciform xanthoma usually is found in the oral mucosa, but also has been seen in the anogenital area and other sites. It also can arise in special settings, such as in patients with chronic lymphedema on the legs, recessive dystrophic epidermolysis bullosa, or other conditions.

The etiology is poorly understood. Trauma, irritation, and infection are thought to be contributors to verruciform xanthoma.

One case report associated the disease with human papillomavirus (HPV) infection, but several subsequent case series found no association with HPV, "so it's currently thought not to be related" to HPV, she said.

Pathologists were able to see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells in the papillary dermis (at high magnification). Courtesy Dr. Kathie Huang

Diagnosis: Verruciform Xanthoma

SAN FRANCISCO — Physicians performed several biopsies of the noncrusting, nonulcerating plaque over a period of several months, looking for possible squamous cell carcinoma. Results were negative for cancer but did show epidermal acanthosis.

This and other characteristics seen on histology identified the plaque as verruciform xanthoma, an uncommon and usually benign entity that has been associated with recessive dystrophic epidermolysis bullosa in only three previous case reports, Dr. Kathie Huang reported at the annual meeting of the Pacific Dermatologic Association.

Verruciform xanthoma can mimic squamous cell carcinoma and warrants a biopsy for evaluation.

Atypia and carcinoma can arise within verruciform xanthoma, according to rare case reports, so it requires close follow-up, said Dr. Huang of Stanford (Calif.) University.

One previous report recommended surgical excision of the lesion to avoid any remote risk of carcinoma, and others called for close follow-up.

In the current case, low-power magnification revealed epidermal acanthosis, papillomatosis, and hyperkeratosis.

On closer inspection, pathologists could see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells filling the papillary dermis. Higher magnification showed clear foamy xanthoma cells in the papillary dermis.

The boy's verruciform xanthoma lesion was surrounded by a difficult-to-heal wound. Recessive dystrophic epidermolysis bullosa is characterized by skin fragility, recurrent trauma, and impaired wound healing.

During trials of treatment with imiquimod, topical antibiotics, and a topical steroid, the verruciform xanthoma plaque maintained its color and quality, and increased some in size before stabilizing.

Dr. Huang and the attending physician, Dr. Anna Bruckner of the university, said they feared that excision of the lesion would increase morbidity by resulting in a nonhealing wound because of the patient's recessive dystrophic epidermolysis bullosa and malnutrition. They opted to manage with close follow-up.

The patient now is 14 years old and doing well, Dr. Huang reported. The verruciform xanthoma plaque has not changed significantly, and has no ulceration or crusting.

In general, verruciform xanthoma usually is found in the oral mucosa, but also has been seen in the anogenital area and other sites. It also can arise in special settings, such as in patients with chronic lymphedema on the legs, recessive dystrophic epidermolysis bullosa, or other conditions.

The etiology is poorly understood. Trauma, irritation, and infection are thought to be contributors to verruciform xanthoma.

One case report associated the disease with human papillomavirus (HPV) infection, but several subsequent case series found no association with HPV, "so it's currently thought not to be related" to HPV, she said.

Pathologists were able to see neutrophilic infiltrate within the epidermis and to the parakeratotic stratum corneum, and clear foamy xanthoma cells in the papillary dermis (at high magnification). Courtesy Dr. Kathie Huang

STANFORD, CALIF. — The most common complaints from parents about a child's musculoskeletal condition stem from usually benign causes that don't need treatment, but addressing them can help alleviate anxiety.

Listen to the parents and acknowledge their concerns, advised Dr. James G. Gamble, professor of orthopedic surgery at Stanford (Calif.) University.

After examining the child, educate the parents about the rotational or angular conditions you find in the child's legs and feet, and get parents actively involved in stretching or massaging the child's limbs, he suggested at a pediatric update sponsored by the university.

He calls this approach OP, for orthopedic psychotherapy.

Recognizing the difference between physiological and pathological conditions of the hips, knees, legs, and feet will let physicians know when to refer to a specialist and when to handle parental complaints. Dr. Gamble reviewed the most common rotational and angular conditions in children that raise concerns about the feet, legs, and knees:

▸ Pigeon toes. Scientifically called metatarsus adductus, this condition presents between birth and 6 months of age, typically as a foot with a concave medial border, a convex lateral border, and a deep plantar crease. Also known as “kidney bean foot,” it can be confused with clubfoot.

Looking at the bottom of the foot, imagine the heel as an oval, and bisect it with an imaginary line that extends up toward the toes. On a normal foot, the line would bisect the gap between the second and third toes. The more the line is toward the last little toe, the more severe the metatarsus adductus.

Check to see if the foot is rigid or supple, because rigidity can be a sign of skewfoot and may require surgery. Finally, check ankle range of motion; limited dorsal flexion may indicate clubfoot or other problems that might need surgery, he said. Also, check the hips, because children with metatarsus adductus have an increased incidence of dislocation.

Refer patients with foot rigidity, limited dorsiflexion at the ankle, or extremely anxious parents to an orthopedic surgeon.

For metatarsus adductus alone, treatment starts with OP and stretching. Casting may help if there's rigidity. Splints or special shoes are an option, but there's no good evidence that any of these change the natural history.

▸ Tibial torsion. Look at the backs of the legs and feet as the child is prone or on a parent's lap, and if the foot is internally rotated or (less commonly) externally rotated, the child has internal or external tibial torsion (also called tibial rotation or version). This is typically seen between 6 months and 3 years of age.

The mainstays of treatment are OP and benign neglect, Dr. Gamble said. Very rarely would he consider surgery or orthotics, and then only in cases of neuromuscular problems such as spina bifida or cerebral palsy or trauma.

▸ Bowlegs or knock-knees. Parents typically get concerned about bowlegs or knock-knees (genu varum or genu valgum) when infants begin to stand and cruise. These conditions typically present between 6 months and 3 years of age.

To differentiate bowlegs from internal tibial torsion, have the child placed supine or sitting with knees in extension. Place the patella in a neutral position and cover the lower leg and foot with your hand. If you see no bowing in the tibial-femoral angle, but when you look under your hand, the foot is turned in about 70 degrees from the distal leg, the condition is not at the knee; it's at the tibia. This is tibial torsion, not genu varum.

If the legs are more angled than bowed, consider the possibility of rickets, vitamin D deficiency, or Blount disease. Referral for an x-ray is warranted only if the condition is unilateral or rapidly progressing, or the patient has asymmetric leg length or a limp.

STANFORD, CALIF. — The most common complaints from parents about a child's musculoskeletal condition stem from usually benign causes that don't need treatment, but addressing them can help alleviate anxiety.

Listen to the parents and acknowledge their concerns, advised Dr. James G. Gamble, professor of orthopedic surgery at Stanford (Calif.) University.

After examining the child, educate the parents about the rotational or angular conditions you find in the child's legs and feet, and get parents actively involved in stretching or massaging the child's limbs, he suggested at a pediatric update sponsored by the university.

He calls this approach OP, for orthopedic psychotherapy.

Recognizing the difference between physiological and pathological conditions of the hips, knees, legs, and feet will let physicians know when to refer to a specialist and when to handle parental complaints. Dr. Gamble reviewed the most common rotational and angular conditions in children that raise concerns about the feet, legs, and knees:

▸ Pigeon toes. Scientifically called metatarsus adductus, this condition presents between birth and 6 months of age, typically as a foot with a concave medial border, a convex lateral border, and a deep plantar crease. Also known as “kidney bean foot,” it can be confused with clubfoot.

Looking at the bottom of the foot, imagine the heel as an oval, and bisect it with an imaginary line that extends up toward the toes. On a normal foot, the line would bisect the gap between the second and third toes. The more the line is toward the last little toe, the more severe the metatarsus adductus.

Check to see if the foot is rigid or supple, because rigidity can be a sign of skewfoot and may require surgery. Finally, check ankle range of motion; limited dorsal flexion may indicate clubfoot or other problems that might need surgery, he said. Also, check the hips, because children with metatarsus adductus have an increased incidence of dislocation.

Refer patients with foot rigidity, limited dorsiflexion at the ankle, or extremely anxious parents to an orthopedic surgeon.

For metatarsus adductus alone, treatment starts with OP and stretching. Casting may help if there's rigidity. Splints or special shoes are an option, but there's no good evidence that any of these change the natural history.

▸ Tibial torsion. Look at the backs of the legs and feet as the child is prone or on a parent's lap, and if the foot is internally rotated or (less commonly) externally rotated, the child has internal or external tibial torsion (also called tibial rotation or version). This is typically seen between 6 months and 3 years of age.

The mainstays of treatment are OP and benign neglect, Dr. Gamble said. Very rarely would he consider surgery or orthotics, and then only in cases of neuromuscular problems such as spina bifida or cerebral palsy or trauma.

▸ Bowlegs or knock-knees. Parents typically get concerned about bowlegs or knock-knees (genu varum or genu valgum) when infants begin to stand and cruise. These conditions typically present between 6 months and 3 years of age.

To differentiate bowlegs from internal tibial torsion, have the child placed supine or sitting with knees in extension. Place the patella in a neutral position and cover the lower leg and foot with your hand. If you see no bowing in the tibial-femoral angle, but when you look under your hand, the foot is turned in about 70 degrees from the distal leg, the condition is not at the knee; it's at the tibia. This is tibial torsion, not genu varum.

If the legs are more angled than bowed, consider the possibility of rickets, vitamin D deficiency, or Blount disease. Referral for an x-ray is warranted only if the condition is unilateral or rapidly progressing, or the patient has asymmetric leg length or a limp.

STANFORD, CALIF. — The most common complaints from parents about a child's musculoskeletal condition stem from usually benign causes that don't need treatment, but addressing them can help alleviate anxiety.

Listen to the parents and acknowledge their concerns, advised Dr. James G. Gamble, professor of orthopedic surgery at Stanford (Calif.) University.

After examining the child, educate the parents about the rotational or angular conditions you find in the child's legs and feet, and get parents actively involved in stretching or massaging the child's limbs, he suggested at a pediatric update sponsored by the university.

He calls this approach OP, for orthopedic psychotherapy.

Recognizing the difference between physiological and pathological conditions of the hips, knees, legs, and feet will let physicians know when to refer to a specialist and when to handle parental complaints. Dr. Gamble reviewed the most common rotational and angular conditions in children that raise concerns about the feet, legs, and knees:

▸ Pigeon toes. Scientifically called metatarsus adductus, this condition presents between birth and 6 months of age, typically as a foot with a concave medial border, a convex lateral border, and a deep plantar crease. Also known as “kidney bean foot,” it can be confused with clubfoot.

Looking at the bottom of the foot, imagine the heel as an oval, and bisect it with an imaginary line that extends up toward the toes. On a normal foot, the line would bisect the gap between the second and third toes. The more the line is toward the last little toe, the more severe the metatarsus adductus.

Check to see if the foot is rigid or supple, because rigidity can be a sign of skewfoot and may require surgery. Finally, check ankle range of motion; limited dorsal flexion may indicate clubfoot or other problems that might need surgery, he said. Also, check the hips, because children with metatarsus adductus have an increased incidence of dislocation.

Refer patients with foot rigidity, limited dorsiflexion at the ankle, or extremely anxious parents to an orthopedic surgeon.

For metatarsus adductus alone, treatment starts with OP and stretching. Casting may help if there's rigidity. Splints or special shoes are an option, but there's no good evidence that any of these change the natural history.

▸ Tibial torsion. Look at the backs of the legs and feet as the child is prone or on a parent's lap, and if the foot is internally rotated or (less commonly) externally rotated, the child has internal or external tibial torsion (also called tibial rotation or version). This is typically seen between 6 months and 3 years of age.

The mainstays of treatment are OP and benign neglect, Dr. Gamble said. Very rarely would he consider surgery or orthotics, and then only in cases of neuromuscular problems such as spina bifida or cerebral palsy or trauma.

▸ Bowlegs or knock-knees. Parents typically get concerned about bowlegs or knock-knees (genu varum or genu valgum) when infants begin to stand and cruise. These conditions typically present between 6 months and 3 years of age.

To differentiate bowlegs from internal tibial torsion, have the child placed supine or sitting with knees in extension. Place the patella in a neutral position and cover the lower leg and foot with your hand. If you see no bowing in the tibial-femoral angle, but when you look under your hand, the foot is turned in about 70 degrees from the distal leg, the condition is not at the knee; it's at the tibia. This is tibial torsion, not genu varum.

If the legs are more angled than bowed, consider the possibility of rickets, vitamin D deficiency, or Blount disease. Referral for an x-ray is warranted only if the condition is unilateral or rapidly progressing, or the patient has asymmetric leg length or a limp.

SAN FRANCISCO — Hyperglycemia and ethnicity each were independently associated with a greater risk for cardiovascular problems in a large, prospective study of 48,444 New Zealanders.

The information came from a New Zealand Ministry of Health program in which primary care physicians across the country were paid to collect and report data on patients with type 2 diabetes who had no history of cardiovascular disease and who were attending free annual visits for their diabetes. The investigators matched the glycemic data with national data on hospital admissions and death records to identify first cardiovascular events (ischemic heart disease, cerebrovascular accident, transient ischemic attack, or peripheral vascular disease), Dr. Paul L. Drury said at the annual scientific sessions of the American Diabetes Association.

During follow-up lasting a median of 2.4 years, 12% of the cohort had a first cardiovascular event. Each 1% increase in hemoglobin A_1c (HbA_1c) level was associated with a hazard ratio of 1.08, a statistically significant increase in risk, reported Dr. Drury, clinical director of diabetes services for the Auckland (New Zealand) District Health Board, and his associates. He has been an advisor to Eli Lilly & Co. and to Merck & Co., which make antidiabetes drugs.

The association between HbA_1c and a first cardiovascular event was significant for both sexes. The results accounted for the effects of age at diagnosis, duration of diabetes, sex, ethnicity, socioeconomic status, smoking, systolic blood pressure, body mass index, the ratio of serum total cholesterol to HDL level, and the urine albumin-creatinine ratio.

Secondary analyses showed that Maori ethnicity was associated with a hazard ratio of 1.3 for developing a cardiovascular event, compared with non-Maori patients, after the researchers controlled for other factors. The study also confirmed the importance of classical risk factors for cardiovascular problems in patients with diabetes.

SAN FRANCISCO — Hyperglycemia and ethnicity each were independently associated with a greater risk for cardiovascular problems in a large, prospective study of 48,444 New Zealanders.

The information came from a New Zealand Ministry of Health program in which primary care physicians across the country were paid to collect and report data on patients with type 2 diabetes who had no history of cardiovascular disease and who were attending free annual visits for their diabetes. The investigators matched the glycemic data with national data on hospital admissions and death records to identify first cardiovascular events (ischemic heart disease, cerebrovascular accident, transient ischemic attack, or peripheral vascular disease), Dr. Paul L. Drury said at the annual scientific sessions of the American Diabetes Association.

During follow-up lasting a median of 2.4 years, 12% of the cohort had a first cardiovascular event. Each 1% increase in hemoglobin A_1c (HbA_1c) level was associated with a hazard ratio of 1.08, a statistically significant increase in risk, reported Dr. Drury, clinical director of diabetes services for the Auckland (New Zealand) District Health Board, and his associates. He has been an advisor to Eli Lilly & Co. and to Merck & Co., which make antidiabetes drugs.

The association between HbA_1c and a first cardiovascular event was significant for both sexes. The results accounted for the effects of age at diagnosis, duration of diabetes, sex, ethnicity, socioeconomic status, smoking, systolic blood pressure, body mass index, the ratio of serum total cholesterol to HDL level, and the urine albumin-creatinine ratio.

Secondary analyses showed that Maori ethnicity was associated with a hazard ratio of 1.3 for developing a cardiovascular event, compared with non-Maori patients, after the researchers controlled for other factors. The study also confirmed the importance of classical risk factors for cardiovascular problems in patients with diabetes.

SAN FRANCISCO — Hyperglycemia and ethnicity each were independently associated with a greater risk for cardiovascular problems in a large, prospective study of 48,444 New Zealanders.

The information came from a New Zealand Ministry of Health program in which primary care physicians across the country were paid to collect and report data on patients with type 2 diabetes who had no history of cardiovascular disease and who were attending free annual visits for their diabetes. The investigators matched the glycemic data with national data on hospital admissions and death records to identify first cardiovascular events (ischemic heart disease, cerebrovascular accident, transient ischemic attack, or peripheral vascular disease), Dr. Paul L. Drury said at the annual scientific sessions of the American Diabetes Association.

During follow-up lasting a median of 2.4 years, 12% of the cohort had a first cardiovascular event. Each 1% increase in hemoglobin A_1c (HbA_1c) level was associated with a hazard ratio of 1.08, a statistically significant increase in risk, reported Dr. Drury, clinical director of diabetes services for the Auckland (New Zealand) District Health Board, and his associates. He has been an advisor to Eli Lilly & Co. and to Merck & Co., which make antidiabetes drugs.

The association between HbA_1c and a first cardiovascular event was significant for both sexes. The results accounted for the effects of age at diagnosis, duration of diabetes, sex, ethnicity, socioeconomic status, smoking, systolic blood pressure, body mass index, the ratio of serum total cholesterol to HDL level, and the urine albumin-creatinine ratio.

Secondary analyses showed that Maori ethnicity was associated with a hazard ratio of 1.3 for developing a cardiovascular event, compared with non-Maori patients, after the researchers controlled for other factors. The study also confirmed the importance of classical risk factors for cardiovascular problems in patients with diabetes.