Heidi Splete

Escitalopram: Age Appears Relevant

Escitalopram failed to significantly improve the symptoms of depression in children aged 6–11 years, but it did appear to improve symptoms in children aged 12–17 years, wrote Dr. Karen Dineen Wagner of the University of Texas, Galveston, and her colleagues.

The study included 264 children and adolescents aged 6–17 years who had been diagnosed with major depressive disorder. The Children's Depression Rating Scale-Revised (CDRS-R) served as the primary outcome measure (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:280–8).

The patients received either a placebo or 10 mg/day of escitalopram (Lexapro) for the first 4 weeks, with the option to increase the dosage up to 20 mg/day for the next 4 weeks, depending on the patient's response to the medication and tolerance.

Overall, the average changes in scores on the CDRS-R from baseline were not significantly different among the 102 escitalopram patients and 115 placebo patients who completed the study (−21.9 vs. −20.2).

However, a later analysis that adjusted for age group revealed significant improvements in CDRS-R scores from baseline among the 77 children aged 12–17 years who took escitalopram, compared with the 80 children aged 12–17 years who took a placebo, based on observed cases (−22.3 vs. −17.8).

In addition, adolescents in the escitalopram group showed significant improvements in symptoms based on several secondary outcome measures, including the Clinical Global Impressions-Severity scale.

Headaches and abdominal pain were the only reported adverse events that occurred in more than 10% of patients in either group, and the discontinuation rate in both groups was 1.5%.

The study was supported by Forest Laboratories, one of many companies from which Dr. Wagner has received research support.

Quetiapine May Ease Mania in Teens

Quetiapine was at least as effective as divalproex in alleviating manic symptoms in adolescents in a randomized, double-blind pilot study, wrote Dr. Melissa P. DelBello and her colleagues at the University of Cincinnati, Ohio.

The 28-day pilot study of 50 adolescents aged 12–18 years was the first known to directly compare an atypical antipsychotic with an antiepileptic in adolescents with mania, the researchers noted (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:305–13).

The study was supported by a grant from AstraZeneca Pharmaceuticals, which markets quetiapine (Seroquel), and is one of the many companies from which Dr. DelBello has received research funding.

The adolescents who received quetiapine started with a 100-mg dose on the first day, which was increased to 400 mg by days 4–7, up to a maximum of 600 mg/day. Those who received divalproex started with a 20-mg/kg dose on the first day, which was increased to achieve serum valproic acid levels of 80–120 μg/mL. At the end of the study, the mean doses were 412 mg/day to 422 mg/day in the quetiapine group, and a valproic acid level of 101 μg/mL in the divalproex group.

Overall, patients in both groups showed statistically significant improvements in their scores on the Young Mania Rating Scale at the end of the study, compared with their baseline scores. However, the response was quicker among the quetiapine patients, compared with divalproex patients, and the overall response rate on the Clinical Global Impressions-Bipolar Version-Improvement scale was significantly greater in the quetiapine group, compared with the divalproex group (72% vs. 40%).

Both medications were well tolerated, and no patient in either group withdrew because of adverse effects. There were no significant differences between the treatment groups in terms of age, gender, race, or age of onset of bipolar disorder.

Depression and Violence

Girls who display depressive symptoms during adolescence are at increased risk for physical violence at the hands of their intimate partners, reported Jocelyn A. Lehrer, Sc.D., of the University of California, San Francisco and her colleagues.

The investigators analyzed interview data from 1,659 girls in grades 7–12 at 80 high schools and 52 middle schools in the United States.

The data were part of the National Longitudinal Study of Adolescent Health, and the girls participated in three waves of at-home interviews; the second wave was 1 year after the first, and the third was 5–6 years after the second (Arch. Pediatr. Adolesc. Med. 2006;160:270–6).

Overall, 28% of girls who reported high levels of depression at baseline also reported some type of intimate partner violence within the past year at the third wave follow-up interview, compared with 17.5% of girls with lower levels of depressive symptoms. High levels of depression were defined as scores of 23 or higher on the Center for Epidemiologic Studies Depression Scale, and the incidence of violence was assessed using self-administered questionnaires.

Each increase of a single standard deviation in baseline depressive symptomatology was associated with a 3% increase in the odds of exposure to either mild, moderate, or severe degrees of partner violence.

Depressive symptoms have been associated with a range of risky behaviors in adolescence, and depressed teens may be more likely than their nondepressed peers to associate with risky peer groups, and to select intimate partners from these groups, the researchers noted. However, the question of whether depressive symptoms independently predict intimate partner violence or simply predict risk for partner violence remains uncertain.

Escitalopram: Age Appears Relevant

Escitalopram failed to significantly improve the symptoms of depression in children aged 6–11 years, but it did appear to improve symptoms in children aged 12–17 years, wrote Dr. Karen Dineen Wagner of the University of Texas, Galveston, and her colleagues.

The study included 264 children and adolescents aged 6–17 years who had been diagnosed with major depressive disorder. The Children's Depression Rating Scale-Revised (CDRS-R) served as the primary outcome measure (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:280–8).

The patients received either a placebo or 10 mg/day of escitalopram (Lexapro) for the first 4 weeks, with the option to increase the dosage up to 20 mg/day for the next 4 weeks, depending on the patient's response to the medication and tolerance.

Overall, the average changes in scores on the CDRS-R from baseline were not significantly different among the 102 escitalopram patients and 115 placebo patients who completed the study (−21.9 vs. −20.2).

However, a later analysis that adjusted for age group revealed significant improvements in CDRS-R scores from baseline among the 77 children aged 12–17 years who took escitalopram, compared with the 80 children aged 12–17 years who took a placebo, based on observed cases (−22.3 vs. −17.8).

In addition, adolescents in the escitalopram group showed significant improvements in symptoms based on several secondary outcome measures, including the Clinical Global Impressions-Severity scale.

Headaches and abdominal pain were the only reported adverse events that occurred in more than 10% of patients in either group, and the discontinuation rate in both groups was 1.5%.

The study was supported by Forest Laboratories, one of many companies from which Dr. Wagner has received research support.

Quetiapine May Ease Mania in Teens

Quetiapine was at least as effective as divalproex in alleviating manic symptoms in adolescents in a randomized, double-blind pilot study, wrote Dr. Melissa P. DelBello and her colleagues at the University of Cincinnati, Ohio.

The 28-day pilot study of 50 adolescents aged 12–18 years was the first known to directly compare an atypical antipsychotic with an antiepileptic in adolescents with mania, the researchers noted (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:305–13).

The study was supported by a grant from AstraZeneca Pharmaceuticals, which markets quetiapine (Seroquel), and is one of the many companies from which Dr. DelBello has received research funding.

The adolescents who received quetiapine started with a 100-mg dose on the first day, which was increased to 400 mg by days 4–7, up to a maximum of 600 mg/day. Those who received divalproex started with a 20-mg/kg dose on the first day, which was increased to achieve serum valproic acid levels of 80–120 μg/mL. At the end of the study, the mean doses were 412 mg/day to 422 mg/day in the quetiapine group, and a valproic acid level of 101 μg/mL in the divalproex group.

Overall, patients in both groups showed statistically significant improvements in their scores on the Young Mania Rating Scale at the end of the study, compared with their baseline scores. However, the response was quicker among the quetiapine patients, compared with divalproex patients, and the overall response rate on the Clinical Global Impressions-Bipolar Version-Improvement scale was significantly greater in the quetiapine group, compared with the divalproex group (72% vs. 40%).

Both medications were well tolerated, and no patient in either group withdrew because of adverse effects. There were no significant differences between the treatment groups in terms of age, gender, race, or age of onset of bipolar disorder.

Depression and Violence

Girls who display depressive symptoms during adolescence are at increased risk for physical violence at the hands of their intimate partners, reported Jocelyn A. Lehrer, Sc.D., of the University of California, San Francisco and her colleagues.

The investigators analyzed interview data from 1,659 girls in grades 7–12 at 80 high schools and 52 middle schools in the United States.

The data were part of the National Longitudinal Study of Adolescent Health, and the girls participated in three waves of at-home interviews; the second wave was 1 year after the first, and the third was 5–6 years after the second (Arch. Pediatr. Adolesc. Med. 2006;160:270–6).

Overall, 28% of girls who reported high levels of depression at baseline also reported some type of intimate partner violence within the past year at the third wave follow-up interview, compared with 17.5% of girls with lower levels of depressive symptoms. High levels of depression were defined as scores of 23 or higher on the Center for Epidemiologic Studies Depression Scale, and the incidence of violence was assessed using self-administered questionnaires.

Each increase of a single standard deviation in baseline depressive symptomatology was associated with a 3% increase in the odds of exposure to either mild, moderate, or severe degrees of partner violence.

Depressive symptoms have been associated with a range of risky behaviors in adolescence, and depressed teens may be more likely than their nondepressed peers to associate with risky peer groups, and to select intimate partners from these groups, the researchers noted. However, the question of whether depressive symptoms independently predict intimate partner violence or simply predict risk for partner violence remains uncertain.

Escitalopram: Age Appears Relevant

Escitalopram failed to significantly improve the symptoms of depression in children aged 6–11 years, but it did appear to improve symptoms in children aged 12–17 years, wrote Dr. Karen Dineen Wagner of the University of Texas, Galveston, and her colleagues.

The study included 264 children and adolescents aged 6–17 years who had been diagnosed with major depressive disorder. The Children's Depression Rating Scale-Revised (CDRS-R) served as the primary outcome measure (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:280–8).

The patients received either a placebo or 10 mg/day of escitalopram (Lexapro) for the first 4 weeks, with the option to increase the dosage up to 20 mg/day for the next 4 weeks, depending on the patient's response to the medication and tolerance.

Overall, the average changes in scores on the CDRS-R from baseline were not significantly different among the 102 escitalopram patients and 115 placebo patients who completed the study (−21.9 vs. −20.2).

However, a later analysis that adjusted for age group revealed significant improvements in CDRS-R scores from baseline among the 77 children aged 12–17 years who took escitalopram, compared with the 80 children aged 12–17 years who took a placebo, based on observed cases (−22.3 vs. −17.8).

In addition, adolescents in the escitalopram group showed significant improvements in symptoms based on several secondary outcome measures, including the Clinical Global Impressions-Severity scale.

Headaches and abdominal pain were the only reported adverse events that occurred in more than 10% of patients in either group, and the discontinuation rate in both groups was 1.5%.

The study was supported by Forest Laboratories, one of many companies from which Dr. Wagner has received research support.

Quetiapine May Ease Mania in Teens

Quetiapine was at least as effective as divalproex in alleviating manic symptoms in adolescents in a randomized, double-blind pilot study, wrote Dr. Melissa P. DelBello and her colleagues at the University of Cincinnati, Ohio.

The 28-day pilot study of 50 adolescents aged 12–18 years was the first known to directly compare an atypical antipsychotic with an antiepileptic in adolescents with mania, the researchers noted (J. Am. Acad. Child Adolesc. Psychiatry 2006;45:305–13).

The study was supported by a grant from AstraZeneca Pharmaceuticals, which markets quetiapine (Seroquel), and is one of the many companies from which Dr. DelBello has received research funding.

The adolescents who received quetiapine started with a 100-mg dose on the first day, which was increased to 400 mg by days 4–7, up to a maximum of 600 mg/day. Those who received divalproex started with a 20-mg/kg dose on the first day, which was increased to achieve serum valproic acid levels of 80–120 μg/mL. At the end of the study, the mean doses were 412 mg/day to 422 mg/day in the quetiapine group, and a valproic acid level of 101 μg/mL in the divalproex group.

Overall, patients in both groups showed statistically significant improvements in their scores on the Young Mania Rating Scale at the end of the study, compared with their baseline scores. However, the response was quicker among the quetiapine patients, compared with divalproex patients, and the overall response rate on the Clinical Global Impressions-Bipolar Version-Improvement scale was significantly greater in the quetiapine group, compared with the divalproex group (72% vs. 40%).

Both medications were well tolerated, and no patient in either group withdrew because of adverse effects. There were no significant differences between the treatment groups in terms of age, gender, race, or age of onset of bipolar disorder.

Depression and Violence

Girls who display depressive symptoms during adolescence are at increased risk for physical violence at the hands of their intimate partners, reported Jocelyn A. Lehrer, Sc.D., of the University of California, San Francisco and her colleagues.

The investigators analyzed interview data from 1,659 girls in grades 7–12 at 80 high schools and 52 middle schools in the United States.

The data were part of the National Longitudinal Study of Adolescent Health, and the girls participated in three waves of at-home interviews; the second wave was 1 year after the first, and the third was 5–6 years after the second (Arch. Pediatr. Adolesc. Med. 2006;160:270–6).

Overall, 28% of girls who reported high levels of depression at baseline also reported some type of intimate partner violence within the past year at the third wave follow-up interview, compared with 17.5% of girls with lower levels of depressive symptoms. High levels of depression were defined as scores of 23 or higher on the Center for Epidemiologic Studies Depression Scale, and the incidence of violence was assessed using self-administered questionnaires.

Each increase of a single standard deviation in baseline depressive symptomatology was associated with a 3% increase in the odds of exposure to either mild, moderate, or severe degrees of partner violence.

Depressive symptoms have been associated with a range of risky behaviors in adolescence, and depressed teens may be more likely than their nondepressed peers to associate with risky peer groups, and to select intimate partners from these groups, the researchers noted. However, the question of whether depressive symptoms independently predict intimate partner violence or simply predict risk for partner violence remains uncertain.

WASHINGTON – The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression can affect children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress as a result of parental depression that the children's normal coping skills are unable to handle the initial stress and the children therefore develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin of the University of South Carolina, Columbia.

Dr. Hankin and his associates conducted a longitudinal study that included 421 8th and 10th -grade students from 18 suburban high schools in Chicago. About 55% were female and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

In addition, parental depressive symptoms contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said. The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

In general, children of depressed parents are at increased risk of psychopathology resulting from internalizing disorders such as depression and anxiety and externalizing disorders such as oppositional disorder and aggression. Children with depressed parents are also more likely to demonstrate impairment in situations concerning school, social competency, and self-esteem.

In addition, the stress caused by a parent's depression disrupts the quality of the parent and child interaction. Such stress also limits the ability of the parent to be available to the child to mitigate the child's daily stressors, Dr. Hankin said.

KATHRYN DALES

WASHINGTON – The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression can affect children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress as a result of parental depression that the children's normal coping skills are unable to handle the initial stress and the children therefore develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin of the University of South Carolina, Columbia.

Dr. Hankin and his associates conducted a longitudinal study that included 421 8th and 10th -grade students from 18 suburban high schools in Chicago. About 55% were female and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

In addition, parental depressive symptoms contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said. The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

In general, children of depressed parents are at increased risk of psychopathology resulting from internalizing disorders such as depression and anxiety and externalizing disorders such as oppositional disorder and aggression. Children with depressed parents are also more likely to demonstrate impairment in situations concerning school, social competency, and self-esteem.

In addition, the stress caused by a parent's depression disrupts the quality of the parent and child interaction. Such stress also limits the ability of the parent to be available to the child to mitigate the child's daily stressors, Dr. Hankin said.

KATHRYN DALES

WASHINGTON – The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression can affect children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress as a result of parental depression that the children's normal coping skills are unable to handle the initial stress and the children therefore develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin of the University of South Carolina, Columbia.

Dr. Hankin and his associates conducted a longitudinal study that included 421 8th and 10th -grade students from 18 suburban high schools in Chicago. About 55% were female and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

In addition, parental depressive symptoms contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said. The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

In general, children of depressed parents are at increased risk of psychopathology resulting from internalizing disorders such as depression and anxiety and externalizing disorders such as oppositional disorder and aggression. Children with depressed parents are also more likely to demonstrate impairment in situations concerning school, social competency, and self-esteem.

In addition, the stress caused by a parent's depression disrupts the quality of the parent and child interaction. Such stress also limits the ability of the parent to be available to the child to mitigate the child's daily stressors, Dr. Hankin said.

KATHRYN DALES

SAN DIEGO — Tumors travel within the nerve structure, so if a Mohs surgeon has a habit of taking superficial margins, he or she will miss perineural tumors, Dr. Alexander Miller said at a meeting sponsored by the American Society for Mohs Surgery.

The nerve structure includes the endoneurium (nerve fibers), perineurium (mostly collagen), and epineurium (connective tissue). All these components vary with the nerve size, and tumors can travel through all of them.

"A perineural tumor doesn't care which nerve it gets into, and it will go anywhere and in any direction," Dr. Miller said. "It could attack several nerves simultaneously," said Dr. Miller of the University of California, Irvine.

About 60%–70% of perineural tumors are asymptomatic and unknown to the patient. With symptomatic tumors, patients report burning, aching, numbness, or even a complete lack of sensation. The nerves are rarely palpable, although they may be more palpable at points where they cross over bones.

Although most perineural invasion is localized, there are cases in which it travels far beyond the general body of the tumor. "Your challenge is to discriminate between localized and not localized," he said. The majority of perineural tumors are localized to areas within 1 cm or less of the general body of the tumor. That said, some invasions extend several centimeters beyond the general body of the tumor, Dr. Miller said.

"Perineural tumors are hard to see under the microscope, and some people forget to look," he said.

Tumors that are most likely to become perineurally invasive are basal cell carcinoma and squamous cell carcinoma, but microcystic adnexal carcinoma, neurotropic malignant melanoma, and other adnexal tumors, particularly salivary or sweat gland tumors, also are candidates for perineural invasion.

An estimated 1% of basal cell carcinomas have perineural invasion. Those most likely to become perineural are morphealike, micronodular, metatypical, and basal cells invading as long arms of tumor surrounded by concentric fibrous sleeves of collagen.

About 3%–4% of squamous cell carcinomas are perineural, usually those that are moderately to poorly differentiated, and show tumor spreading like a narrow cord.

Squamous cell carcinomas more than 2 cm in diameter or greater than 4-mm thickness are more likely to be perineural than smaller ones; if they are 8 mm in thickness the risk is substantial.

Most microcystic adnexal carcinomas, approximately 80%, invade perineurally and subclinically, and it is crucial for the Mohs surgeon to be aware of this, Dr. Miller said. "Take a wider margin than you would with other tumors, be careful about tracking out the edges, and get good-quality slides."

Regardless of the type of tumor, tumors that are perineurally invasive share a uniform histology and display similar behaviors.

"They all pretty much look the same once they get into the perineural space," Dr. Miller said. The tumor cells can be tightly packed, clustered, or in a line. "In order to tell the tumor of origin, you have to go back to the original histology and look elsewhere on the slide" he said.

The pattern of growth can be spotty or concentric, and perineural tumors tend to be multifocal. "It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve," he said.

"Be aware of multifocality in the subcutaneous layer," Dr. Miller advised. "If you have poor-quality slides that are consistently destroying fat, you may miss crucial structures." Obvious inflammation around a nerve is a helpful indicator of perineural invasion, he added.

Tumor depth has been shown to correlate with perineural invasion, as has tumor recurrence and fibrous sleeve growth. Also, pay attention to nerve orientation on the microscope slides. A tumor may invade concentrically around the nerve, or just crawl along a portion of the nerve circumference. When a tumor invades along only one edge of a nerve, it can easily be missed.

"Multiple Mohs sections and slides must be examined for perineural tumor, or you will miss it," Dr. Miller emphasized.

"When perineural tumors recur, they are unpleasant; they are deep, and they can grow subclinically for a long time," Dr. Miller said. "Meticulous, compulsive evaluation is needed to successfully treat these patients and prevent recurrence."

'It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve.' DR. MILLER

SAN DIEGO — Tumors travel within the nerve structure, so if a Mohs surgeon has a habit of taking superficial margins, he or she will miss perineural tumors, Dr. Alexander Miller said at a meeting sponsored by the American Society for Mohs Surgery.

The nerve structure includes the endoneurium (nerve fibers), perineurium (mostly collagen), and epineurium (connective tissue). All these components vary with the nerve size, and tumors can travel through all of them.

"A perineural tumor doesn't care which nerve it gets into, and it will go anywhere and in any direction," Dr. Miller said. "It could attack several nerves simultaneously," said Dr. Miller of the University of California, Irvine.

About 60%–70% of perineural tumors are asymptomatic and unknown to the patient. With symptomatic tumors, patients report burning, aching, numbness, or even a complete lack of sensation. The nerves are rarely palpable, although they may be more palpable at points where they cross over bones.

Although most perineural invasion is localized, there are cases in which it travels far beyond the general body of the tumor. "Your challenge is to discriminate between localized and not localized," he said. The majority of perineural tumors are localized to areas within 1 cm or less of the general body of the tumor. That said, some invasions extend several centimeters beyond the general body of the tumor, Dr. Miller said.

"Perineural tumors are hard to see under the microscope, and some people forget to look," he said.

Tumors that are most likely to become perineurally invasive are basal cell carcinoma and squamous cell carcinoma, but microcystic adnexal carcinoma, neurotropic malignant melanoma, and other adnexal tumors, particularly salivary or sweat gland tumors, also are candidates for perineural invasion.

An estimated 1% of basal cell carcinomas have perineural invasion. Those most likely to become perineural are morphealike, micronodular, metatypical, and basal cells invading as long arms of tumor surrounded by concentric fibrous sleeves of collagen.

About 3%–4% of squamous cell carcinomas are perineural, usually those that are moderately to poorly differentiated, and show tumor spreading like a narrow cord.

Squamous cell carcinomas more than 2 cm in diameter or greater than 4-mm thickness are more likely to be perineural than smaller ones; if they are 8 mm in thickness the risk is substantial.

Most microcystic adnexal carcinomas, approximately 80%, invade perineurally and subclinically, and it is crucial for the Mohs surgeon to be aware of this, Dr. Miller said. "Take a wider margin than you would with other tumors, be careful about tracking out the edges, and get good-quality slides."

Regardless of the type of tumor, tumors that are perineurally invasive share a uniform histology and display similar behaviors.

"They all pretty much look the same once they get into the perineural space," Dr. Miller said. The tumor cells can be tightly packed, clustered, or in a line. "In order to tell the tumor of origin, you have to go back to the original histology and look elsewhere on the slide" he said.

The pattern of growth can be spotty or concentric, and perineural tumors tend to be multifocal. "It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve," he said.

"Be aware of multifocality in the subcutaneous layer," Dr. Miller advised. "If you have poor-quality slides that are consistently destroying fat, you may miss crucial structures." Obvious inflammation around a nerve is a helpful indicator of perineural invasion, he added.

Tumor depth has been shown to correlate with perineural invasion, as has tumor recurrence and fibrous sleeve growth. Also, pay attention to nerve orientation on the microscope slides. A tumor may invade concentrically around the nerve, or just crawl along a portion of the nerve circumference. When a tumor invades along only one edge of a nerve, it can easily be missed.

"Multiple Mohs sections and slides must be examined for perineural tumor, or you will miss it," Dr. Miller emphasized.

"When perineural tumors recur, they are unpleasant; they are deep, and they can grow subclinically for a long time," Dr. Miller said. "Meticulous, compulsive evaluation is needed to successfully treat these patients and prevent recurrence."

'It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve.' DR. MILLER

SAN DIEGO — Tumors travel within the nerve structure, so if a Mohs surgeon has a habit of taking superficial margins, he or she will miss perineural tumors, Dr. Alexander Miller said at a meeting sponsored by the American Society for Mohs Surgery.

The nerve structure includes the endoneurium (nerve fibers), perineurium (mostly collagen), and epineurium (connective tissue). All these components vary with the nerve size, and tumors can travel through all of them.

"A perineural tumor doesn't care which nerve it gets into, and it will go anywhere and in any direction," Dr. Miller said. "It could attack several nerves simultaneously," said Dr. Miller of the University of California, Irvine.

About 60%–70% of perineural tumors are asymptomatic and unknown to the patient. With symptomatic tumors, patients report burning, aching, numbness, or even a complete lack of sensation. The nerves are rarely palpable, although they may be more palpable at points where they cross over bones.

Although most perineural invasion is localized, there are cases in which it travels far beyond the general body of the tumor. "Your challenge is to discriminate between localized and not localized," he said. The majority of perineural tumors are localized to areas within 1 cm or less of the general body of the tumor. That said, some invasions extend several centimeters beyond the general body of the tumor, Dr. Miller said.

"Perineural tumors are hard to see under the microscope, and some people forget to look," he said.

Tumors that are most likely to become perineurally invasive are basal cell carcinoma and squamous cell carcinoma, but microcystic adnexal carcinoma, neurotropic malignant melanoma, and other adnexal tumors, particularly salivary or sweat gland tumors, also are candidates for perineural invasion.

An estimated 1% of basal cell carcinomas have perineural invasion. Those most likely to become perineural are morphealike, micronodular, metatypical, and basal cells invading as long arms of tumor surrounded by concentric fibrous sleeves of collagen.

About 3%–4% of squamous cell carcinomas are perineural, usually those that are moderately to poorly differentiated, and show tumor spreading like a narrow cord.

Squamous cell carcinomas more than 2 cm in diameter or greater than 4-mm thickness are more likely to be perineural than smaller ones; if they are 8 mm in thickness the risk is substantial.

Most microcystic adnexal carcinomas, approximately 80%, invade perineurally and subclinically, and it is crucial for the Mohs surgeon to be aware of this, Dr. Miller said. "Take a wider margin than you would with other tumors, be careful about tracking out the edges, and get good-quality slides."

Regardless of the type of tumor, tumors that are perineurally invasive share a uniform histology and display similar behaviors.

"They all pretty much look the same once they get into the perineural space," Dr. Miller said. The tumor cells can be tightly packed, clustered, or in a line. "In order to tell the tumor of origin, you have to go back to the original histology and look elsewhere on the slide" he said.

The pattern of growth can be spotty or concentric, and perineural tumors tend to be multifocal. "It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve," he said.

"Be aware of multifocality in the subcutaneous layer," Dr. Miller advised. "If you have poor-quality slides that are consistently destroying fat, you may miss crucial structures." Obvious inflammation around a nerve is a helpful indicator of perineural invasion, he added.

Tumor depth has been shown to correlate with perineural invasion, as has tumor recurrence and fibrous sleeve growth. Also, pay attention to nerve orientation on the microscope slides. A tumor may invade concentrically around the nerve, or just crawl along a portion of the nerve circumference. When a tumor invades along only one edge of a nerve, it can easily be missed.

"Multiple Mohs sections and slides must be examined for perineural tumor, or you will miss it," Dr. Miller emphasized.

"When perineural tumors recur, they are unpleasant; they are deep, and they can grow subclinically for a long time," Dr. Miller said. "Meticulous, compulsive evaluation is needed to successfully treat these patients and prevent recurrence."

'It's crucial to realize that perineural tumors can affect more than one nerve or multiple branches of the same nerve.' DR. MILLER

SAN DIEGO — The use of zinc chloride fixative paste may be controversial, but its judicious application can increase the melanoma-clearing properties of Mohs surgery, Dr. Norman A. Brooks said at a meeting sponsored by the American Society for Mohs Surgery.

"Zinc chloride fixative paste is an amazing substance; it has the ability to cure cancer right out of the bone," said Dr. Brooks, a Mohs surgeon in private practice in Encino, Calif.

Application of the paste has been shown to freeze melanomatous tissue in place. This process kills the tissue, which can then be removed using Mohs surgery.

Dr. Frederic Mohs did not invent the paste, but he did fine-tune the standard formula, which is still in use today.

The use of zinc chloride fixative paste for the treatment of skin conditions has not been approved by the Food and Drug Administration, and patients should not apply it themselves or buy it online. The paste is powerful, toxic, and potentially scar causing, and it must be handled carefully, Dr. Brooks said.

It does, however, appear to work. Studies have shown higher cure rates in melanoma patients when the paste was used prior to excision of the cancer with Mohs surgery, he noted.

The application of zinc chloride fixative paste is a two-step process. The paste can't penetrate the outer keratin layer of the skin, so it's necessary to apply a saturated dichloroacetic or trichloroacetic acid solution to the area. When the area turns white, that means the acid has dissolved the keratin and the paste can be applied. The paste is applied in a layer 1- to 2-mm thick, with a narrow margin around the clinical melanoma that includes subclinical extensions. A dry, sterile cotton ball is then applied with clear plastic adhesive tape as an occlusive dressing to hold the paste in place.

Approximately 24 hours later, the killed tissue is excised and a wall of white, fixed tissue will be visible, Dr. Brooks said. The excised specimen can be preserved in formaldehyde, embedded in paraffin, and sectioned for examination.

The use of zinc chloride paste is not a substitution for Mohs surgery, but it can be a supplement to it. "If used preoperatively, after a biopsy, it can cure patients even more effectively than surgery alone," Dr. Brooks said.

Zinc chloride paste does not get the publicity of cancer treatments such as interferon because it is not FDA approved, Dr. Brooks noted. Companies that might consider seeking FDA approval balk at the multimillion-dollar cost of a toxicity study. Although the paste is made of naturally occurring ingredients, the toxicity study is cost prohibitive and no company has been willing to put up the money.

"I don't blame them. That would be financially insane," Dr. Brooks said. But that doesn't mean Mohs surgeons can't use the paste if they get informed consent from patients.

"You need to tell the patient that this is not an FDA-approved drug; it is a naturally occurring substance, and it can improve the outcome of the surgery by reducing the risk of recurrence," Dr. Brooks said.

The formula for zinc paste perfected by Dr. Mohs has been published and can be found in the Mohs surgery literature.

Many patients with cancer are now receiving preoperative treatments such as chemotherapy, and the use of zinc chloride fixative paste prior to excision of the cancer can be another effective strategy when properly applied, Dr. Brooks said.

A biopsy was performed on a 1.8-mm-thick amelanotic melanoma of the left arm.

Zinc chloride fixative paste was applied to the fresh tissue site with a 2- to 3-mm margin.

A dressing held the zinc chloride paste in place for 24 hours before Mohs excision.

Conventional excision of a deep wide margin was done a week after applying paste.

No sentinel node involvement was seen on this patient at time of fresh tissue excision. Photos courtesy Dr. Norman A. Brooks

SAN DIEGO — The use of zinc chloride fixative paste may be controversial, but its judicious application can increase the melanoma-clearing properties of Mohs surgery, Dr. Norman A. Brooks said at a meeting sponsored by the American Society for Mohs Surgery.

"Zinc chloride fixative paste is an amazing substance; it has the ability to cure cancer right out of the bone," said Dr. Brooks, a Mohs surgeon in private practice in Encino, Calif.

Application of the paste has been shown to freeze melanomatous tissue in place. This process kills the tissue, which can then be removed using Mohs surgery.

Dr. Frederic Mohs did not invent the paste, but he did fine-tune the standard formula, which is still in use today.

The use of zinc chloride fixative paste for the treatment of skin conditions has not been approved by the Food and Drug Administration, and patients should not apply it themselves or buy it online. The paste is powerful, toxic, and potentially scar causing, and it must be handled carefully, Dr. Brooks said.

It does, however, appear to work. Studies have shown higher cure rates in melanoma patients when the paste was used prior to excision of the cancer with Mohs surgery, he noted.

The application of zinc chloride fixative paste is a two-step process. The paste can't penetrate the outer keratin layer of the skin, so it's necessary to apply a saturated dichloroacetic or trichloroacetic acid solution to the area. When the area turns white, that means the acid has dissolved the keratin and the paste can be applied. The paste is applied in a layer 1- to 2-mm thick, with a narrow margin around the clinical melanoma that includes subclinical extensions. A dry, sterile cotton ball is then applied with clear plastic adhesive tape as an occlusive dressing to hold the paste in place.

Approximately 24 hours later, the killed tissue is excised and a wall of white, fixed tissue will be visible, Dr. Brooks said. The excised specimen can be preserved in formaldehyde, embedded in paraffin, and sectioned for examination.

The use of zinc chloride paste is not a substitution for Mohs surgery, but it can be a supplement to it. "If used preoperatively, after a biopsy, it can cure patients even more effectively than surgery alone," Dr. Brooks said.

Zinc chloride paste does not get the publicity of cancer treatments such as interferon because it is not FDA approved, Dr. Brooks noted. Companies that might consider seeking FDA approval balk at the multimillion-dollar cost of a toxicity study. Although the paste is made of naturally occurring ingredients, the toxicity study is cost prohibitive and no company has been willing to put up the money.

"I don't blame them. That would be financially insane," Dr. Brooks said. But that doesn't mean Mohs surgeons can't use the paste if they get informed consent from patients.

"You need to tell the patient that this is not an FDA-approved drug; it is a naturally occurring substance, and it can improve the outcome of the surgery by reducing the risk of recurrence," Dr. Brooks said.

The formula for zinc paste perfected by Dr. Mohs has been published and can be found in the Mohs surgery literature.

Many patients with cancer are now receiving preoperative treatments such as chemotherapy, and the use of zinc chloride fixative paste prior to excision of the cancer can be another effective strategy when properly applied, Dr. Brooks said.

A biopsy was performed on a 1.8-mm-thick amelanotic melanoma of the left arm.

Zinc chloride fixative paste was applied to the fresh tissue site with a 2- to 3-mm margin.

A dressing held the zinc chloride paste in place for 24 hours before Mohs excision.

Conventional excision of a deep wide margin was done a week after applying paste.

No sentinel node involvement was seen on this patient at time of fresh tissue excision. Photos courtesy Dr. Norman A. Brooks

SAN DIEGO — The use of zinc chloride fixative paste may be controversial, but its judicious application can increase the melanoma-clearing properties of Mohs surgery, Dr. Norman A. Brooks said at a meeting sponsored by the American Society for Mohs Surgery.

"Zinc chloride fixative paste is an amazing substance; it has the ability to cure cancer right out of the bone," said Dr. Brooks, a Mohs surgeon in private practice in Encino, Calif.

Application of the paste has been shown to freeze melanomatous tissue in place. This process kills the tissue, which can then be removed using Mohs surgery.

Dr. Frederic Mohs did not invent the paste, but he did fine-tune the standard formula, which is still in use today.

The use of zinc chloride fixative paste for the treatment of skin conditions has not been approved by the Food and Drug Administration, and patients should not apply it themselves or buy it online. The paste is powerful, toxic, and potentially scar causing, and it must be handled carefully, Dr. Brooks said.

It does, however, appear to work. Studies have shown higher cure rates in melanoma patients when the paste was used prior to excision of the cancer with Mohs surgery, he noted.

The application of zinc chloride fixative paste is a two-step process. The paste can't penetrate the outer keratin layer of the skin, so it's necessary to apply a saturated dichloroacetic or trichloroacetic acid solution to the area. When the area turns white, that means the acid has dissolved the keratin and the paste can be applied. The paste is applied in a layer 1- to 2-mm thick, with a narrow margin around the clinical melanoma that includes subclinical extensions. A dry, sterile cotton ball is then applied with clear plastic adhesive tape as an occlusive dressing to hold the paste in place.

Approximately 24 hours later, the killed tissue is excised and a wall of white, fixed tissue will be visible, Dr. Brooks said. The excised specimen can be preserved in formaldehyde, embedded in paraffin, and sectioned for examination.

The use of zinc chloride paste is not a substitution for Mohs surgery, but it can be a supplement to it. "If used preoperatively, after a biopsy, it can cure patients even more effectively than surgery alone," Dr. Brooks said.

Zinc chloride paste does not get the publicity of cancer treatments such as interferon because it is not FDA approved, Dr. Brooks noted. Companies that might consider seeking FDA approval balk at the multimillion-dollar cost of a toxicity study. Although the paste is made of naturally occurring ingredients, the toxicity study is cost prohibitive and no company has been willing to put up the money.

"I don't blame them. That would be financially insane," Dr. Brooks said. But that doesn't mean Mohs surgeons can't use the paste if they get informed consent from patients.

"You need to tell the patient that this is not an FDA-approved drug; it is a naturally occurring substance, and it can improve the outcome of the surgery by reducing the risk of recurrence," Dr. Brooks said.

The formula for zinc paste perfected by Dr. Mohs has been published and can be found in the Mohs surgery literature.

Many patients with cancer are now receiving preoperative treatments such as chemotherapy, and the use of zinc chloride fixative paste prior to excision of the cancer can be another effective strategy when properly applied, Dr. Brooks said.

A biopsy was performed on a 1.8-mm-thick amelanotic melanoma of the left arm.

Zinc chloride fixative paste was applied to the fresh tissue site with a 2- to 3-mm margin.

A dressing held the zinc chloride paste in place for 24 hours before Mohs excision.

Conventional excision of a deep wide margin was done a week after applying paste.

No sentinel node involvement was seen on this patient at time of fresh tissue excision. Photos courtesy Dr. Norman A. Brooks

SAN DIEGO — Some closures may be too complex for inexperienced Mohs surgeons, but even novices can successfully close most of their cases if they have an understanding of how skin flaps move and a willingness to see the possibilities in the two simple skin movements—the fusiform and the z-plasty—that underlie all flap closures, Dr. Kenneth G. Gross said at a meeting sponsored by the American Society for Mohs Surgery.

It helps to think of flap movement as occurring in two dimensions.

"The majority of skin flaps can be explained simply by exploring what makes a fusiform work," Dr. Gross said.

Fusiform flaps generally have 30-degree angles at their tips, based on principles of plane geometry, but the skin is not a flat plane, and whether a lesion will close with 30-degree angles depends on the anatomic location.

"The purpose of making 30-degree angles at the ends of the fusiform is to allow closure without a standing cone," said Dr. Gross, a dermatologic surgeon in private practice in San Diego.

The fusiform consists of three components: the central defect to be closed (depicted as a circle) and two Burow's triangles.

The short axis of the defect usually forms the short axis of the fusiform. The surgeon uses the Burow's triangles at each end of the fusiform to bring the defect to 30-degree angles or to the angles necessary to close the wound without creating a standing cone at the ends of the excision.

The Burow's triangles also can be rotated at the ends of the fusiform as needed to achieve the best cosmetic result. "The Burow's triangle can even be rotated 90 degrees," Dr. Gross pointed out. "You should do whatever type of Burow's triangle is needed to make the best possible closure."

If the location of the defect prevents the use of a Burow's triangle at one or both ends of the fusiform, the surgeon can offset the Burow's triangles, Dr. Gross explained.

"This will result in the creation of what we call an advancement or a rotation flap. If the Burow's triangle is offset to two sides, the result will be a bilateral flap, such as the bilateral advancement or the A to T flap," he commented.

"If the surgeon is in doubt about how to close a wound, he or she may start by drawing a fusiform and then [assessing] whether the fusiform lies in the relaxed skin tension lines and whether it causes distortion of surrounding important anatomic structures," Dr. Gross advised.

If the fusiform does interfere with important anatomy, the surgeon must decide where to offset the Burow's triangles at one or both ends of the fusiform—thereby creating an advancement or rotation flap that doesn't interfere with important anatomy or degrade the cosmetic result.

He noted that about 90% of his Mohs closures are variations of rotation flaps.

Although rotation flaps are generally larger than other types of flaps, Dr. Gross believes that they yield better cosmetic results than transposition flaps because the resulting scar lines can usually be placed in junctions between anatomic units.

Transposition flaps are based primarily on z-plasty movement.

"If you understand the movement of a z-plasty, you will understand how all transposition flaps move and why they move the way they do," Dr. Gross said at the meeting.

Think of a z-plasty as two Burow's triangles sharing a common side, called the central limb. When planning a z-plasty, think about using imaginary skin hooks to pull the central limb longer, Dr. Gross said.

While the central limb lengthens and rotates, there is concomitant shortening of tissue approximately 90 degrees from the axis of the central limb.

The amount of central limb lengthening, and the amount of rotation and shortening in the other axis, is determined by the total of both angles of the Burow's triangles in the z-plasty.

"You can combine 45-degree and 90-degree angles in the same z-plasty, and in fact the Burow's triangles of transposition flaps never have the same-sized angles," Dr. Gross said.

This is the reason some surgeons don't recognize the z-plasties that lie at the heart of all transposition flaps: They are accustomed to seeing z-plasties in textbooks that are drawn with equal angles.

As long as there is sufficient tissue in the opposite direction to allow for shortening without disrupting the surrounding anatomy, as well as enough skin laxity, the surgeon can use whatever size z-plasty angles are needed to produce the amount of central limb lengthening that will close the defect.

The three transposition flaps most often discussed and used by dermatologic surgeons are the Limberg, Webster, and Dufourmentel flaps.

The only difference among them is the total angle of the z-plasties used to create the flaps. The larger the sum of the total angles of the z-plasty of the transposition flap, the greater the lengthening and degree of rotation of the central limb and the greater the shortening of tissue in the opposite axis.

These actions result in the movement of tissue into the defect known as a transposition flap closure. Overall, the amount of tissue that is "wasted" is similar in both a z-plasty and a rotation flap, Dr. Gross said.

SAN DIEGO — Some closures may be too complex for inexperienced Mohs surgeons, but even novices can successfully close most of their cases if they have an understanding of how skin flaps move and a willingness to see the possibilities in the two simple skin movements—the fusiform and the z-plasty—that underlie all flap closures, Dr. Kenneth G. Gross said at a meeting sponsored by the American Society for Mohs Surgery.

It helps to think of flap movement as occurring in two dimensions.

"The majority of skin flaps can be explained simply by exploring what makes a fusiform work," Dr. Gross said.

Fusiform flaps generally have 30-degree angles at their tips, based on principles of plane geometry, but the skin is not a flat plane, and whether a lesion will close with 30-degree angles depends on the anatomic location.

"The purpose of making 30-degree angles at the ends of the fusiform is to allow closure without a standing cone," said Dr. Gross, a dermatologic surgeon in private practice in San Diego.

The fusiform consists of three components: the central defect to be closed (depicted as a circle) and two Burow's triangles.

The short axis of the defect usually forms the short axis of the fusiform. The surgeon uses the Burow's triangles at each end of the fusiform to bring the defect to 30-degree angles or to the angles necessary to close the wound without creating a standing cone at the ends of the excision.

The Burow's triangles also can be rotated at the ends of the fusiform as needed to achieve the best cosmetic result. "The Burow's triangle can even be rotated 90 degrees," Dr. Gross pointed out. "You should do whatever type of Burow's triangle is needed to make the best possible closure."

If the location of the defect prevents the use of a Burow's triangle at one or both ends of the fusiform, the surgeon can offset the Burow's triangles, Dr. Gross explained.

"This will result in the creation of what we call an advancement or a rotation flap. If the Burow's triangle is offset to two sides, the result will be a bilateral flap, such as the bilateral advancement or the A to T flap," he commented.

"If the surgeon is in doubt about how to close a wound, he or she may start by drawing a fusiform and then [assessing] whether the fusiform lies in the relaxed skin tension lines and whether it causes distortion of surrounding important anatomic structures," Dr. Gross advised.

If the fusiform does interfere with important anatomy, the surgeon must decide where to offset the Burow's triangles at one or both ends of the fusiform—thereby creating an advancement or rotation flap that doesn't interfere with important anatomy or degrade the cosmetic result.

He noted that about 90% of his Mohs closures are variations of rotation flaps.

Although rotation flaps are generally larger than other types of flaps, Dr. Gross believes that they yield better cosmetic results than transposition flaps because the resulting scar lines can usually be placed in junctions between anatomic units.

Transposition flaps are based primarily on z-plasty movement.

"If you understand the movement of a z-plasty, you will understand how all transposition flaps move and why they move the way they do," Dr. Gross said at the meeting.

Think of a z-plasty as two Burow's triangles sharing a common side, called the central limb. When planning a z-plasty, think about using imaginary skin hooks to pull the central limb longer, Dr. Gross said.

While the central limb lengthens and rotates, there is concomitant shortening of tissue approximately 90 degrees from the axis of the central limb.

The amount of central limb lengthening, and the amount of rotation and shortening in the other axis, is determined by the total of both angles of the Burow's triangles in the z-plasty.

"You can combine 45-degree and 90-degree angles in the same z-plasty, and in fact the Burow's triangles of transposition flaps never have the same-sized angles," Dr. Gross said.

This is the reason some surgeons don't recognize the z-plasties that lie at the heart of all transposition flaps: They are accustomed to seeing z-plasties in textbooks that are drawn with equal angles.

As long as there is sufficient tissue in the opposite direction to allow for shortening without disrupting the surrounding anatomy, as well as enough skin laxity, the surgeon can use whatever size z-plasty angles are needed to produce the amount of central limb lengthening that will close the defect.

The three transposition flaps most often discussed and used by dermatologic surgeons are the Limberg, Webster, and Dufourmentel flaps.

The only difference among them is the total angle of the z-plasties used to create the flaps. The larger the sum of the total angles of the z-plasty of the transposition flap, the greater the lengthening and degree of rotation of the central limb and the greater the shortening of tissue in the opposite axis.

These actions result in the movement of tissue into the defect known as a transposition flap closure. Overall, the amount of tissue that is "wasted" is similar in both a z-plasty and a rotation flap, Dr. Gross said.

SAN DIEGO — Some closures may be too complex for inexperienced Mohs surgeons, but even novices can successfully close most of their cases if they have an understanding of how skin flaps move and a willingness to see the possibilities in the two simple skin movements—the fusiform and the z-plasty—that underlie all flap closures, Dr. Kenneth G. Gross said at a meeting sponsored by the American Society for Mohs Surgery.

It helps to think of flap movement as occurring in two dimensions.

"The majority of skin flaps can be explained simply by exploring what makes a fusiform work," Dr. Gross said.

Fusiform flaps generally have 30-degree angles at their tips, based on principles of plane geometry, but the skin is not a flat plane, and whether a lesion will close with 30-degree angles depends on the anatomic location.

"The purpose of making 30-degree angles at the ends of the fusiform is to allow closure without a standing cone," said Dr. Gross, a dermatologic surgeon in private practice in San Diego.

The fusiform consists of three components: the central defect to be closed (depicted as a circle) and two Burow's triangles.

The short axis of the defect usually forms the short axis of the fusiform. The surgeon uses the Burow's triangles at each end of the fusiform to bring the defect to 30-degree angles or to the angles necessary to close the wound without creating a standing cone at the ends of the excision.

The Burow's triangles also can be rotated at the ends of the fusiform as needed to achieve the best cosmetic result. "The Burow's triangle can even be rotated 90 degrees," Dr. Gross pointed out. "You should do whatever type of Burow's triangle is needed to make the best possible closure."

If the location of the defect prevents the use of a Burow's triangle at one or both ends of the fusiform, the surgeon can offset the Burow's triangles, Dr. Gross explained.

"This will result in the creation of what we call an advancement or a rotation flap. If the Burow's triangle is offset to two sides, the result will be a bilateral flap, such as the bilateral advancement or the A to T flap," he commented.

"If the surgeon is in doubt about how to close a wound, he or she may start by drawing a fusiform and then [assessing] whether the fusiform lies in the relaxed skin tension lines and whether it causes distortion of surrounding important anatomic structures," Dr. Gross advised.

If the fusiform does interfere with important anatomy, the surgeon must decide where to offset the Burow's triangles at one or both ends of the fusiform—thereby creating an advancement or rotation flap that doesn't interfere with important anatomy or degrade the cosmetic result.

He noted that about 90% of his Mohs closures are variations of rotation flaps.

Although rotation flaps are generally larger than other types of flaps, Dr. Gross believes that they yield better cosmetic results than transposition flaps because the resulting scar lines can usually be placed in junctions between anatomic units.

Transposition flaps are based primarily on z-plasty movement.

"If you understand the movement of a z-plasty, you will understand how all transposition flaps move and why they move the way they do," Dr. Gross said at the meeting.

Think of a z-plasty as two Burow's triangles sharing a common side, called the central limb. When planning a z-plasty, think about using imaginary skin hooks to pull the central limb longer, Dr. Gross said.

While the central limb lengthens and rotates, there is concomitant shortening of tissue approximately 90 degrees from the axis of the central limb.

The amount of central limb lengthening, and the amount of rotation and shortening in the other axis, is determined by the total of both angles of the Burow's triangles in the z-plasty.

"You can combine 45-degree and 90-degree angles in the same z-plasty, and in fact the Burow's triangles of transposition flaps never have the same-sized angles," Dr. Gross said.

This is the reason some surgeons don't recognize the z-plasties that lie at the heart of all transposition flaps: They are accustomed to seeing z-plasties in textbooks that are drawn with equal angles.

As long as there is sufficient tissue in the opposite direction to allow for shortening without disrupting the surrounding anatomy, as well as enough skin laxity, the surgeon can use whatever size z-plasty angles are needed to produce the amount of central limb lengthening that will close the defect.

The three transposition flaps most often discussed and used by dermatologic surgeons are the Limberg, Webster, and Dufourmentel flaps.

The only difference among them is the total angle of the z-plasties used to create the flaps. The larger the sum of the total angles of the z-plasty of the transposition flap, the greater the lengthening and degree of rotation of the central limb and the greater the shortening of tissue in the opposite axis.

These actions result in the movement of tissue into the defect known as a transposition flap closure. Overall, the amount of tissue that is "wasted" is similar in both a z-plasty and a rotation flap, Dr. Gross said.

WASHINGTON — Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham, who is also a professor of psychology at the university, and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups—no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate.

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication—0.15 mg/kg three times daily—had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15 mg/kg dose in combination with behavior modification, but the highest dose—0.6 mg/kg—produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 m g/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects—a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received behavior modification remained off medication at school during the fall semester, compared with children who received none (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

WASHINGTON — Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham, who is also a professor of psychology at the university, and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups—no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate.

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication—0.15 mg/kg three times daily—had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15 mg/kg dose in combination with behavior modification, but the highest dose—0.6 mg/kg—produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 m g/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects—a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received behavior modification remained off medication at school during the fall semester, compared with children who received none (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

WASHINGTON — Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham, who is also a professor of psychology at the university, and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups—no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate.

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication—0.15 mg/kg three times daily—had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15 mg/kg dose in combination with behavior modification, but the highest dose—0.6 mg/kg—produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 m g/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects—a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received behavior modification remained off medication at school during the fall semester, compared with children who received none (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

WASHINGTON — Diabetic patients with severe skin infections had greater improvement when treated with meropenem than with imipenem-cilastatin, Dr. John M. Embil reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Skin and skin-structure infections are a perpetual problem for many diabetic patients, and may require surgical intervention if left untreated, wrote Dr. Embil of the University of Manitoba, Winnipeg, Canada.

The international, randomized, double-blind study included 1,037 hospitalized patients with complicated skin infections, 398 of whom were diabetic.

The clinical cure rate was 86% among the 204 diabetic patients who received a 500-mg intravenous dose of meropenem every 8 hours, compared with 72% among the 194 diabetic patients who received the same dosing regimen of imipenem-cilastatin. The cure rate among the nondiabetic patients treated with meropenem (87%) was similar to the rate in those treated with imipenem-cilastatin (89%).

Overall, meropenem was associated with slightly higher cure rates for all groups of pathogens—aerobic gram-negative, aerobic gram-positive, anaerobic, and polymicrobial—compared with imipenem-cilastatin, but the differences were not statistically significant. More than 40% of the pathogens were gram-negative aerobic or anaerobic organisms, and 29% of the Staphylococcus aureus isolates showed methicillin resistance. A similar spectrum of pathogens appeared in both diabetic and nondiabetic patients.

The study was sponsored in part by AstraZeneca, and the meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Diabetic patients with severe skin infections had greater improvement when treated with meropenem than with imipenem-cilastatin, Dr. John M. Embil reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Skin and skin-structure infections are a perpetual problem for many diabetic patients, and may require surgical intervention if left untreated, wrote Dr. Embil of the University of Manitoba, Winnipeg, Canada.

The international, randomized, double-blind study included 1,037 hospitalized patients with complicated skin infections, 398 of whom were diabetic.

The clinical cure rate was 86% among the 204 diabetic patients who received a 500-mg intravenous dose of meropenem every 8 hours, compared with 72% among the 194 diabetic patients who received the same dosing regimen of imipenem-cilastatin. The cure rate among the nondiabetic patients treated with meropenem (87%) was similar to the rate in those treated with imipenem-cilastatin (89%).

Overall, meropenem was associated with slightly higher cure rates for all groups of pathogens—aerobic gram-negative, aerobic gram-positive, anaerobic, and polymicrobial—compared with imipenem-cilastatin, but the differences were not statistically significant. More than 40% of the pathogens were gram-negative aerobic or anaerobic organisms, and 29% of the Staphylococcus aureus isolates showed methicillin resistance. A similar spectrum of pathogens appeared in both diabetic and nondiabetic patients.

The study was sponsored in part by AstraZeneca, and the meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Diabetic patients with severe skin infections had greater improvement when treated with meropenem than with imipenem-cilastatin, Dr. John M. Embil reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Skin and skin-structure infections are a perpetual problem for many diabetic patients, and may require surgical intervention if left untreated, wrote Dr. Embil of the University of Manitoba, Winnipeg, Canada.

The international, randomized, double-blind study included 1,037 hospitalized patients with complicated skin infections, 398 of whom were diabetic.

The clinical cure rate was 86% among the 204 diabetic patients who received a 500-mg intravenous dose of meropenem every 8 hours, compared with 72% among the 194 diabetic patients who received the same dosing regimen of imipenem-cilastatin. The cure rate among the nondiabetic patients treated with meropenem (87%) was similar to the rate in those treated with imipenem-cilastatin (89%).

Overall, meropenem was associated with slightly higher cure rates for all groups of pathogens—aerobic gram-negative, aerobic gram-positive, anaerobic, and polymicrobial—compared with imipenem-cilastatin, but the differences were not statistically significant. More than 40% of the pathogens were gram-negative aerobic or anaerobic organisms, and 29% of the Staphylococcus aureus isolates showed methicillin resistance. A similar spectrum of pathogens appeared in both diabetic and nondiabetic patients.

The study was sponsored in part by AstraZeneca, and the meeting was sponsored by the American Society for Microbiology.

BAL HARBOUR, FLA. — Tracking the cause of allergic contact dermatitis in children requires investigation of all possible avenues of exposure, from toys and clothes to personal hygiene products and foods.

“Patients can receive a dose of allergen in many different ways,” Dr. Sharon E. Jacob said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Allergic contact dermatitis hypersensitivity reactions proceed through three phases: sensitization, challenge, and resolution, said Dr. Jacob, director of the contact dermatitis clinic at the university.

Sensitization occurs when the patient is first exposed to the allergen, but it takes about 21 days.

“Most people don't have a reaction on immediate exposure to an allergen,” Dr. Jacob said. After the patient is sensitized and rechallenged, or reexposed, it takes about 48–96 hours for the skin to react.

“This is important, because patients often won't remember what they did 2–3 days before a rash appeared,” she noted.

The first step in evaluating a child for allergic contact dermatitis is to take an in-depth history. “Look for temporal relationships; ask when the child gets better or worse,” Dr. Jacob said. Consider the child's age, gender, and demographics. Examine the distribution pattern of the rash, which may provide a clue to its origin. For example, a pattern of perioral dermatitis may suggest an allergy to fragrances or balsam of Peru, whereas earlobe dermatitis in a young girl with pierced ears suggests a metal allergy. Also ask about the child's activities, including day care and travel, and even what jewelry he or she wears.

Next, select the most likely allergens for patch testing given the patient's history. Be sure to use allergen concentrations that are safe in children. There are currently no commercially available allergy testing kits designed for the pediatric population, Dr. Jacob noted.

The most common sources of contact dermatitis in children include nickel, fragrances/flavorings, thimerosal, chromium, formaldehyde, cobalt, lanolin, paraphenylenediamine, neomycin, bacitracin, and cocamidopropyl betaine.

Nickel remains the most prevalent contact allergen among children. Nickel exposure can come from many sources, including paper clips, jewelry, front snaps on jeans, and foods. Certain foods—including chocolate, asparagus, soy, and oatmeal—contain high amounts of nickel.

“Allergic contact dermatitis is a dose-dependent phenomenon, and trigger foods may contribute a significant dose,” Dr. Jacob explained.

For example, a 12-year-old girl might wear jeans and earrings, eat both chocolate and oatmeal, and touch paper clips in a single day. These seemingly unrelated items all contain nickel and have the potential to exacerbate contact dermatitis in a sensitized patient. “It's a bit like being Sherlock Holmes and putting the puzzle pieces together—once you know the allergens—to figure out the exposures,” Dr. Jacob said.

Fragrances and flavorings are common causes of contact dermatitis, and they appear in many products that patients routinely use. “We need to remind patients that 'unscented' is in fact a blocking fragrance. Many parents believe that unscented is the same as 'fragrance free,'” Dr. Jacob noted. Two common fragrance allergens, cinnamic alcohol and cinnamic aldehyde, are components of balsam of Peru. These substances can be ingredients in soaps and shampoos, as well as in many foods, including tomato-based products such as ketchup, and artificially flavored soft drinks. Thimerosal is a preservative found in some vaccines and some medications, such as Neo-Synephrine pediatric formula and L'Oreal Miracle Wear mascara, Dr. Jacob noted.

Chromium is another metal salt that appears in products ranging from cement to leather to match heads. People who keep matchbooks in their pockets can have an allergic reaction to chromate in the shape of a patch on the leg where the matchbook was placed, Dr. Jacob noted. Again, food can increase the dose of the allergen. Orthodontic braces or dental fillings may contain chromium, as do apples (especially the peels); a combination of these items can exacerbate contact dermatitis in an allergic patient.

Bacitracin is another common allergen in the United States. It is one of the components of Neosporin, and this over-the-counter antibiotic ointment has been associated with anaphylaxis in allergic patients, Dr. Jacob warned.

Paraphenylenediamine is an oxidation chemical ingredient that often is used as a hair dye. More recently, it has been used in henna tattoo dyes to make them last longer, despite a Food and Drug Administration warning against the use of this chemical on the skin, Dr. Jacob said.

Formaldehyde and formaldehyde-releasing preservatives are common allergens for children. They are present in many child care products, including Johnson & Johnson baby shampoo, Baby Magic wash, and Water Babies sunscreen, as well as other cosmetics, baby wipes, and personal hygiene products. Aspartame, or NutraSweet, degrades into methanol, which in turn is metabolized in the liver and releases formaldehyde, Dr. Jacob noted. Children with a formaldehyde allergy may find that their condition resolves when they eliminate diet sodas containing NutraSweet and other NutraSweet-containing products from their diets, she said.

Cocamidopropyl betaine is a detergent that appears in many soaps, shampoos, and toothpastes, including Cetaphil and Dove products, and Colgate toothpaste. Patients with this allergy may present with dermatitis behind the ear, where shampoo tends to collect; this allergen should be suspected in children with persistent hand dermatitis.

When treating children with allergic contact dermatitis, allowing time for questions and patient education after the patch test is paramount, Dr. Jacob emphasized. Also, recognize the discomfort and frustration children may feel about the patch test process, and about the elimination or reduction of favorite foods, jewelry, or other products. Provide information about safe alternatives. “I can't stress this enough,” she said.

Databases such as the Contact Allergen Replacement Database, available through the American Contact Dermatitis Society (www.contactderm.org

Allergic contact dermatitis can be caused by anything from toys to food. Courtesy Dr. Sharon E. Jacob

BAL HARBOUR, FLA. — Tracking the cause of allergic contact dermatitis in children requires investigation of all possible avenues of exposure, from toys and clothes to personal hygiene products and foods.

“Patients can receive a dose of allergen in many different ways,” Dr. Sharon E. Jacob said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Allergic contact dermatitis hypersensitivity reactions proceed through three phases: sensitization, challenge, and resolution, said Dr. Jacob, director of the contact dermatitis clinic at the university.

Sensitization occurs when the patient is first exposed to the allergen, but it takes about 21 days.

“Most people don't have a reaction on immediate exposure to an allergen,” Dr. Jacob said. After the patient is sensitized and rechallenged, or reexposed, it takes about 48–96 hours for the skin to react.

“This is important, because patients often won't remember what they did 2–3 days before a rash appeared,” she noted.

The first step in evaluating a child for allergic contact dermatitis is to take an in-depth history. “Look for temporal relationships; ask when the child gets better or worse,” Dr. Jacob said. Consider the child's age, gender, and demographics. Examine the distribution pattern of the rash, which may provide a clue to its origin. For example, a pattern of perioral dermatitis may suggest an allergy to fragrances or balsam of Peru, whereas earlobe dermatitis in a young girl with pierced ears suggests a metal allergy. Also ask about the child's activities, including day care and travel, and even what jewelry he or she wears.

Next, select the most likely allergens for patch testing given the patient's history. Be sure to use allergen concentrations that are safe in children. There are currently no commercially available allergy testing kits designed for the pediatric population, Dr. Jacob noted.

The most common sources of contact dermatitis in children include nickel, fragrances/flavorings, thimerosal, chromium, formaldehyde, cobalt, lanolin, paraphenylenediamine, neomycin, bacitracin, and cocamidopropyl betaine.

Nickel remains the most prevalent contact allergen among children. Nickel exposure can come from many sources, including paper clips, jewelry, front snaps on jeans, and foods. Certain foods—including chocolate, asparagus, soy, and oatmeal—contain high amounts of nickel.

“Allergic contact dermatitis is a dose-dependent phenomenon, and trigger foods may contribute a significant dose,” Dr. Jacob explained.

For example, a 12-year-old girl might wear jeans and earrings, eat both chocolate and oatmeal, and touch paper clips in a single day. These seemingly unrelated items all contain nickel and have the potential to exacerbate contact dermatitis in a sensitized patient. “It's a bit like being Sherlock Holmes and putting the puzzle pieces together—once you know the allergens—to figure out the exposures,” Dr. Jacob said.

Fragrances and flavorings are common causes of contact dermatitis, and they appear in many products that patients routinely use. “We need to remind patients that 'unscented' is in fact a blocking fragrance. Many parents believe that unscented is the same as 'fragrance free,'” Dr. Jacob noted. Two common fragrance allergens, cinnamic alcohol and cinnamic aldehyde, are components of balsam of Peru. These substances can be ingredients in soaps and shampoos, as well as in many foods, including tomato-based products such as ketchup, and artificially flavored soft drinks. Thimerosal is a preservative found in some vaccines and some medications, such as Neo-Synephrine pediatric formula and L'Oreal Miracle Wear mascara, Dr. Jacob noted.

Chromium is another metal salt that appears in products ranging from cement to leather to match heads. People who keep matchbooks in their pockets can have an allergic reaction to chromate in the shape of a patch on the leg where the matchbook was placed, Dr. Jacob noted. Again, food can increase the dose of the allergen. Orthodontic braces or dental fillings may contain chromium, as do apples (especially the peels); a combination of these items can exacerbate contact dermatitis in an allergic patient.

Bacitracin is another common allergen in the United States. It is one of the components of Neosporin, and this over-the-counter antibiotic ointment has been associated with anaphylaxis in allergic patients, Dr. Jacob warned.

Paraphenylenediamine is an oxidation chemical ingredient that often is used as a hair dye. More recently, it has been used in henna tattoo dyes to make them last longer, despite a Food and Drug Administration warning against the use of this chemical on the skin, Dr. Jacob said.

Formaldehyde and formaldehyde-releasing preservatives are common allergens for children. They are present in many child care products, including Johnson & Johnson baby shampoo, Baby Magic wash, and Water Babies sunscreen, as well as other cosmetics, baby wipes, and personal hygiene products. Aspartame, or NutraSweet, degrades into methanol, which in turn is metabolized in the liver and releases formaldehyde, Dr. Jacob noted. Children with a formaldehyde allergy may find that their condition resolves when they eliminate diet sodas containing NutraSweet and other NutraSweet-containing products from their diets, she said.

Cocamidopropyl betaine is a detergent that appears in many soaps, shampoos, and toothpastes, including Cetaphil and Dove products, and Colgate toothpaste. Patients with this allergy may present with dermatitis behind the ear, where shampoo tends to collect; this allergen should be suspected in children with persistent hand dermatitis.

When treating children with allergic contact dermatitis, allowing time for questions and patient education after the patch test is paramount, Dr. Jacob emphasized. Also, recognize the discomfort and frustration children may feel about the patch test process, and about the elimination or reduction of favorite foods, jewelry, or other products. Provide information about safe alternatives. “I can't stress this enough,” she said.

Databases such as the Contact Allergen Replacement Database, available through the American Contact Dermatitis Society (www.contactderm.org

Allergic contact dermatitis can be caused by anything from toys to food. Courtesy Dr. Sharon E. Jacob

BAL HARBOUR, FLA. — Tracking the cause of allergic contact dermatitis in children requires investigation of all possible avenues of exposure, from toys and clothes to personal hygiene products and foods.

“Patients can receive a dose of allergen in many different ways,” Dr. Sharon E. Jacob said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Allergic contact dermatitis hypersensitivity reactions proceed through three phases: sensitization, challenge, and resolution, said Dr. Jacob, director of the contact dermatitis clinic at the university.

Sensitization occurs when the patient is first exposed to the allergen, but it takes about 21 days.

“Most people don't have a reaction on immediate exposure to an allergen,” Dr. Jacob said. After the patient is sensitized and rechallenged, or reexposed, it takes about 48–96 hours for the skin to react.

“This is important, because patients often won't remember what they did 2–3 days before a rash appeared,” she noted.

The first step in evaluating a child for allergic contact dermatitis is to take an in-depth history. “Look for temporal relationships; ask when the child gets better or worse,” Dr. Jacob said. Consider the child's age, gender, and demographics. Examine the distribution pattern of the rash, which may provide a clue to its origin. For example, a pattern of perioral dermatitis may suggest an allergy to fragrances or balsam of Peru, whereas earlobe dermatitis in a young girl with pierced ears suggests a metal allergy. Also ask about the child's activities, including day care and travel, and even what jewelry he or she wears.

Next, select the most likely allergens for patch testing given the patient's history. Be sure to use allergen concentrations that are safe in children. There are currently no commercially available allergy testing kits designed for the pediatric population, Dr. Jacob noted.

The most common sources of contact dermatitis in children include nickel, fragrances/flavorings, thimerosal, chromium, formaldehyde, cobalt, lanolin, paraphenylenediamine, neomycin, bacitracin, and cocamidopropyl betaine.

Nickel remains the most prevalent contact allergen among children. Nickel exposure can come from many sources, including paper clips, jewelry, front snaps on jeans, and foods. Certain foods—including chocolate, asparagus, soy, and oatmeal—contain high amounts of nickel.

“Allergic contact dermatitis is a dose-dependent phenomenon, and trigger foods may contribute a significant dose,” Dr. Jacob explained.

For example, a 12-year-old girl might wear jeans and earrings, eat both chocolate and oatmeal, and touch paper clips in a single day. These seemingly unrelated items all contain nickel and have the potential to exacerbate contact dermatitis in a sensitized patient. “It's a bit like being Sherlock Holmes and putting the puzzle pieces together—once you know the allergens—to figure out the exposures,” Dr. Jacob said.

Fragrances and flavorings are common causes of contact dermatitis, and they appear in many products that patients routinely use. “We need to remind patients that 'unscented' is in fact a blocking fragrance. Many parents believe that unscented is the same as 'fragrance free,'” Dr. Jacob noted. Two common fragrance allergens, cinnamic alcohol and cinnamic aldehyde, are components of balsam of Peru. These substances can be ingredients in soaps and shampoos, as well as in many foods, including tomato-based products such as ketchup, and artificially flavored soft drinks. Thimerosal is a preservative found in some vaccines and some medications, such as Neo-Synephrine pediatric formula and L'Oreal Miracle Wear mascara, Dr. Jacob noted.

Chromium is another metal salt that appears in products ranging from cement to leather to match heads. People who keep matchbooks in their pockets can have an allergic reaction to chromate in the shape of a patch on the leg where the matchbook was placed, Dr. Jacob noted. Again, food can increase the dose of the allergen. Orthodontic braces or dental fillings may contain chromium, as do apples (especially the peels); a combination of these items can exacerbate contact dermatitis in an allergic patient.

Bacitracin is another common allergen in the United States. It is one of the components of Neosporin, and this over-the-counter antibiotic ointment has been associated with anaphylaxis in allergic patients, Dr. Jacob warned.

Paraphenylenediamine is an oxidation chemical ingredient that often is used as a hair dye. More recently, it has been used in henna tattoo dyes to make them last longer, despite a Food and Drug Administration warning against the use of this chemical on the skin, Dr. Jacob said.

Formaldehyde and formaldehyde-releasing preservatives are common allergens for children. They are present in many child care products, including Johnson & Johnson baby shampoo, Baby Magic wash, and Water Babies sunscreen, as well as other cosmetics, baby wipes, and personal hygiene products. Aspartame, or NutraSweet, degrades into methanol, which in turn is metabolized in the liver and releases formaldehyde, Dr. Jacob noted. Children with a formaldehyde allergy may find that their condition resolves when they eliminate diet sodas containing NutraSweet and other NutraSweet-containing products from their diets, she said.

Cocamidopropyl betaine is a detergent that appears in many soaps, shampoos, and toothpastes, including Cetaphil and Dove products, and Colgate toothpaste. Patients with this allergy may present with dermatitis behind the ear, where shampoo tends to collect; this allergen should be suspected in children with persistent hand dermatitis.

When treating children with allergic contact dermatitis, allowing time for questions and patient education after the patch test is paramount, Dr. Jacob emphasized. Also, recognize the discomfort and frustration children may feel about the patch test process, and about the elimination or reduction of favorite foods, jewelry, or other products. Provide information about safe alternatives. “I can't stress this enough,” she said.

Databases such as the Contact Allergen Replacement Database, available through the American Contact Dermatitis Society (www.contactderm.org

Allergic contact dermatitis can be caused by anything from toys to food. Courtesy Dr. Sharon E. Jacob

WASHINGTON — Depressed patients with infections who were treated concomitantly with linezolid and antidepressants showed no evidence of developing serotonin syndrome due to drug interactions, compared with similar patients taking other antibiotics, Dr. Meryl H. Mendelson of Pfizer Global Pharmaceuticals, New York, and colleagues reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Despite this evidence against dangerous drug interactions, data from postmarketing case reports suggest the need to closely observe patients on linezolid and concomitant antidepressants. Physicians should consider discontinuing one or both if patients show signs or symptoms of serotonin syndrome, the investigators said.

Limited clinical evidence suggests that linezolid may weakly inhibit monoamine oxidase and may interact with adrenergic or serotonergic agents, they noted.

A total of 117 adults who received SSRIs and linezolid were matched with 127 patients who received SSRIs and non-linezolid antibiotics—including amoxicillin-clavulanate, cefadroxil, and vancomycin—in phase III and IV drug comparison trials.

Among additional patients being treated with tricyclic or other non-SSRI antidepressants, 112 patients receiving linezolid were matched with 115 patients receiving non-linezolid antibiotics. Both groups were treated concomitantly with antibiotics for approximately 8 days.

Symptoms were classified in three groups based on directly observed or patient-reported adverse events. (See chart.) Adverse event rates were similar among patients on linezolid and other antibiotics.

The study was sponsored by Pfizer, and the meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Depressed patients with infections who were treated concomitantly with linezolid and antidepressants showed no evidence of developing serotonin syndrome due to drug interactions, compared with similar patients taking other antibiotics, Dr. Meryl H. Mendelson of Pfizer Global Pharmaceuticals, New York, and colleagues reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Despite this evidence against dangerous drug interactions, data from postmarketing case reports suggest the need to closely observe patients on linezolid and concomitant antidepressants. Physicians should consider discontinuing one or both if patients show signs or symptoms of serotonin syndrome, the investigators said.

Limited clinical evidence suggests that linezolid may weakly inhibit monoamine oxidase and may interact with adrenergic or serotonergic agents, they noted.

A total of 117 adults who received SSRIs and linezolid were matched with 127 patients who received SSRIs and non-linezolid antibiotics—including amoxicillin-clavulanate, cefadroxil, and vancomycin—in phase III and IV drug comparison trials.

Among additional patients being treated with tricyclic or other non-SSRI antidepressants, 112 patients receiving linezolid were matched with 115 patients receiving non-linezolid antibiotics. Both groups were treated concomitantly with antibiotics for approximately 8 days.

Symptoms were classified in three groups based on directly observed or patient-reported adverse events. (See chart.) Adverse event rates were similar among patients on linezolid and other antibiotics.

The study was sponsored by Pfizer, and the meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Depressed patients with infections who were treated concomitantly with linezolid and antidepressants showed no evidence of developing serotonin syndrome due to drug interactions, compared with similar patients taking other antibiotics, Dr. Meryl H. Mendelson of Pfizer Global Pharmaceuticals, New York, and colleagues reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Despite this evidence against dangerous drug interactions, data from postmarketing case reports suggest the need to closely observe patients on linezolid and concomitant antidepressants. Physicians should consider discontinuing one or both if patients show signs or symptoms of serotonin syndrome, the investigators said.

Limited clinical evidence suggests that linezolid may weakly inhibit monoamine oxidase and may interact with adrenergic or serotonergic agents, they noted.

A total of 117 adults who received SSRIs and linezolid were matched with 127 patients who received SSRIs and non-linezolid antibiotics—including amoxicillin-clavulanate, cefadroxil, and vancomycin—in phase III and IV drug comparison trials.

Among additional patients being treated with tricyclic or other non-SSRI antidepressants, 112 patients receiving linezolid were matched with 115 patients receiving non-linezolid antibiotics. Both groups were treated concomitantly with antibiotics for approximately 8 days.

Symptoms were classified in three groups based on directly observed or patient-reported adverse events. (See chart.) Adverse event rates were similar among patients on linezolid and other antibiotics.

The study was sponsored by Pfizer, and the meeting was sponsored by the American Society for Microbiology.

A combination MMR-varicella vaccine can be substituted for the second dose of the MMR vaccine or for the second doses of coadministered MMR and varicella vaccines in children aged 4–6 years, reported Dr. Keith S. Reisinger of Primary Physicians Research in Pittsburgh, and his associates.

Dr. Reisinger and his colleagues found postvaccination seropositivity rates of nearly 100% for the combination measles, mumps, rubella, and varicella vaccine (ProQuad) in a randomized, double-blind multicenter study sponsored by Merck & Co., including 799 healthy children (Pediatrics 2006;117:265–72).

Dr. Reisinger serves as a speaker for Merck and receives research money from the company.

The children had received their primary doses of the measles, mumps, and rubella vaccine (Merck-brand MMRII vaccine) and the varicella vaccine (Varivax) at age 12 months or older at least 1 month before their enrollment in the study.

A total of 399 children received ProQuad as a single injection, plus a placebo, while 205 children received the standard MMRII plus a placebo, and 195 received MMRII plus Varivax. About half the children (53%) were male, most (79%) were white, and their mean age was 4 years.

Overall, the immune responses to all four viruses, as measured by geometric mean titers (GMTs), in children who received ProQuad were statistically similar to those in children who received the other vaccines, although there were differences in GMTs with respect to the individual viruses. The GMTs of antibodies to mumps alone were statistically lower in the ProQuad group, compared with the other groups, but the GMTs of antibodies to rubella and varicella in the ProQuad group were higher, compared with the other groups, Dr. Reisinger and hisassociates wrote.

No severe vaccine-related adverse events were reported, and the percentages of any adverse events were similar among the groups. The most common problems were fever, nasopharyngitis, and cough. There were no significant differences in injection-site adverse experiences in the ProQuad group, compared with the other groups.

The concentration of varicella vaccine virus was higher in the ProQuad vaccine than in the current Varivax varicella vaccine, but the concentrations of measles, mumps, and rubella viruses were the same as those in the current MMRII vaccine.

“The use of [measles, mumps, rubella, and varicella] MMRV will increase varicella protection in a similar fashion that MMR did for lagging mumps and rubella vaccine utilization in the early ′70s,” Dr. Reisinger said. Secondly, some parents and physicians are concerned about the high number of injections that infants receive in the first 2 years of life. The use of MMRV will be helpful in reducing the number of shots.

“Although the above factors are important, the largest issue to me is the need [for the United States] to move toward a two-dose varicella policy. Every vaccine has a primary failure rate. For MMR this primary failure rate is corrected through the recommendation of two doses.

“If the United States adopts a second varicella dose recommendation (as surely it must), the combined MMRV administered at 4–6 years of age will be the vaccine of choice to accomplish this,” he said.

A combination MMR-varicella vaccine can be substituted for the second dose of the MMR vaccine or for the second doses of coadministered MMR and varicella vaccines in children aged 4–6 years, reported Dr. Keith S. Reisinger of Primary Physicians Research in Pittsburgh, and his associates.

Dr. Reisinger and his colleagues found postvaccination seropositivity rates of nearly 100% for the combination measles, mumps, rubella, and varicella vaccine (ProQuad) in a randomized, double-blind multicenter study sponsored by Merck & Co., including 799 healthy children (Pediatrics 2006;117:265–72).

Dr. Reisinger serves as a speaker for Merck and receives research money from the company.

The children had received their primary doses of the measles, mumps, and rubella vaccine (Merck-brand MMRII vaccine) and the varicella vaccine (Varivax) at age 12 months or older at least 1 month before their enrollment in the study.

A total of 399 children received ProQuad as a single injection, plus a placebo, while 205 children received the standard MMRII plus a placebo, and 195 received MMRII plus Varivax. About half the children (53%) were male, most (79%) were white, and their mean age was 4 years.

Overall, the immune responses to all four viruses, as measured by geometric mean titers (GMTs), in children who received ProQuad were statistically similar to those in children who received the other vaccines, although there were differences in GMTs with respect to the individual viruses. The GMTs of antibodies to mumps alone were statistically lower in the ProQuad group, compared with the other groups, but the GMTs of antibodies to rubella and varicella in the ProQuad group were higher, compared with the other groups, Dr. Reisinger and hisassociates wrote.

No severe vaccine-related adverse events were reported, and the percentages of any adverse events were similar among the groups. The most common problems were fever, nasopharyngitis, and cough. There were no significant differences in injection-site adverse experiences in the ProQuad group, compared with the other groups.

The concentration of varicella vaccine virus was higher in the ProQuad vaccine than in the current Varivax varicella vaccine, but the concentrations of measles, mumps, and rubella viruses were the same as those in the current MMRII vaccine.

“The use of [measles, mumps, rubella, and varicella] MMRV will increase varicella protection in a similar fashion that MMR did for lagging mumps and rubella vaccine utilization in the early ′70s,” Dr. Reisinger said. Secondly, some parents and physicians are concerned about the high number of injections that infants receive in the first 2 years of life. The use of MMRV will be helpful in reducing the number of shots.

“Although the above factors are important, the largest issue to me is the need [for the United States] to move toward a two-dose varicella policy. Every vaccine has a primary failure rate. For MMR this primary failure rate is corrected through the recommendation of two doses.

“If the United States adopts a second varicella dose recommendation (as surely it must), the combined MMRV administered at 4–6 years of age will be the vaccine of choice to accomplish this,” he said.

A combination MMR-varicella vaccine can be substituted for the second dose of the MMR vaccine or for the second doses of coadministered MMR and varicella vaccines in children aged 4–6 years, reported Dr. Keith S. Reisinger of Primary Physicians Research in Pittsburgh, and his associates.

Dr. Reisinger and his colleagues found postvaccination seropositivity rates of nearly 100% for the combination measles, mumps, rubella, and varicella vaccine (ProQuad) in a randomized, double-blind multicenter study sponsored by Merck & Co., including 799 healthy children (Pediatrics 2006;117:265–72).

Dr. Reisinger serves as a speaker for Merck and receives research money from the company.

The children had received their primary doses of the measles, mumps, and rubella vaccine (Merck-brand MMRII vaccine) and the varicella vaccine (Varivax) at age 12 months or older at least 1 month before their enrollment in the study.

A total of 399 children received ProQuad as a single injection, plus a placebo, while 205 children received the standard MMRII plus a placebo, and 195 received MMRII plus Varivax. About half the children (53%) were male, most (79%) were white, and their mean age was 4 years.

Overall, the immune responses to all four viruses, as measured by geometric mean titers (GMTs), in children who received ProQuad were statistically similar to those in children who received the other vaccines, although there were differences in GMTs with respect to the individual viruses. The GMTs of antibodies to mumps alone were statistically lower in the ProQuad group, compared with the other groups, but the GMTs of antibodies to rubella and varicella in the ProQuad group were higher, compared with the other groups, Dr. Reisinger and hisassociates wrote.

No severe vaccine-related adverse events were reported, and the percentages of any adverse events were similar among the groups. The most common problems were fever, nasopharyngitis, and cough. There were no significant differences in injection-site adverse experiences in the ProQuad group, compared with the other groups.

The concentration of varicella vaccine virus was higher in the ProQuad vaccine than in the current Varivax varicella vaccine, but the concentrations of measles, mumps, and rubella viruses were the same as those in the current MMRII vaccine.

“The use of [measles, mumps, rubella, and varicella] MMRV will increase varicella protection in a similar fashion that MMR did for lagging mumps and rubella vaccine utilization in the early ′70s,” Dr. Reisinger said. Secondly, some parents and physicians are concerned about the high number of injections that infants receive in the first 2 years of life. The use of MMRV will be helpful in reducing the number of shots.

“Although the above factors are important, the largest issue to me is the need [for the United States] to move toward a two-dose varicella policy. Every vaccine has a primary failure rate. For MMR this primary failure rate is corrected through the recommendation of two doses.

“If the United States adopts a second varicella dose recommendation (as surely it must), the combined MMRV administered at 4–6 years of age will be the vaccine of choice to accomplish this,” he said.