Betsy Bates

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and up, reports in the literature suggest.

“We're seeing a surge of cases among younger people,” Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors. It is important to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late “has not changed in years and years,” and hovers around 50%.

White patches and plaques of leukoplakia are telltale signs. Common early presentations are along the posterolateral border and the ventral surface of the tongue–regions of thin, nonkeratinized mucosa and saliva pooling, said Dr. Smith, who reported no potential conflicts of interest.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and up, reports in the literature suggest.

“We're seeing a surge of cases among younger people,” Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors. It is important to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late “has not changed in years and years,” and hovers around 50%.

White patches and plaques of leukoplakia are telltale signs. Common early presentations are along the posterolateral border and the ventral surface of the tongue–regions of thin, nonkeratinized mucosa and saliva pooling, said Dr. Smith, who reported no potential conflicts of interest.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and up, reports in the literature suggest.

“We're seeing a surge of cases among younger people,” Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors. It is important to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late “has not changed in years and years,” and hovers around 50%.

White patches and plaques of leukoplakia are telltale signs. Common early presentations are along the posterolateral border and the ventral surface of the tongue–regions of thin, nonkeratinized mucosa and saliva pooling, said Dr. Smith, who reported no potential conflicts of interest.

SAN FRANCISCO — An unexpected, significant uptick in rheumatoid arthritis incidence among women may point to increased exposure to hormonal and environmental risk factors, although investigators remain unsure of a clear explanation.

“What we had seen over the last 50 years was a continuous decline [in RA incidence] from the 1950s to the [mid] 1990s,” Dr. Hilal Maradit Kremers said during a press briefing at the annual meeting of the American College of Rheumatology. “We were expecting that decline to continue.”

Surprisingly, the trend instead reversed quite dramatically between 1995 and 2004, according to what began as a rather routine update of incidence trends in Olmsted County, Minn., by Dr. Maradit Kremers and her associates at the Mayo Clinic, Rochester, Minn.

The age-adjusted incidence in women was 54 per 100,000 in the post-1995 analysis, compared with 36.4 per 100,000 between 1985 and 2004.

The average age of onset for women was 56.5 years, roughly the same as in previous years.

Among men, the incidence of RA remained steady between 1995 and 2004, at 28.6 per 100,000, compared with previous decades.

Although the Midwestern population included in long-term Mayo Clinic epidemiologic studies underrepresents nonwhite populations, it has the advantage of stability, allowing disease trends to be detected quite accurately. So Dr. Maradit Kremers could say with considerable confidence that “the incidence of this disease is rising again.”

What remains a mystery is why the incidence rate would change, and so rapidly. “This was purely an observational study,” she said. “At this point we can only speculate that some [unknown] risk factors may be operating to increase the occurrence of this disease.”

Smoking, the most well-established risk factor for the development of RA, actually declined among women in the United States between 1990 and 2003, from 23% of women to 19%, according to statistics from the Centers for Disease Control and Prevention.

Obesity, which did escalate during the years of the study, is not generally associated with development of RA, said Dr. Maradit Kremers, a clinical epidemiologist.

Genetics, hormones, diet, and viral exposure have all been proposed as potential risk factors for RA (Scand. J. Rheumatol. 2006;35:169–74).

Since cases in women appear to be driving the recent surge in incidence, hormonal and reproductive factors will undoubtedly be the focus of new scrutiny, she said.

Some 20 studies have explored such risk factors over the years, generally pointing to pregnancy and oral contraceptive use as protective.

The respective roles of childbearing age, total number of children, breast-feeding, and use of hormone therapy are as yet unclear, she said.

Dr. Maradit Kremers said the study has “important implications” for policy makers, especially with regard to resource allocation for a disease suddenly on the rise after years of decline.

“This worrisome increase in occurrence of RA not only offers us clues into the causes of RA, but also highlights the need for more research into the causes and treatment of this devastating disease,” Dr. Sherine Gabriel, a Mayo Clinic rheumatologist and lead author of the study, said in a statement.

Dr. Maradit Kremers disclosed that she has received research grants and/or consultant fees from Pfizer Inc. and Amgen Inc., makers of drugs prescribed for rheumatoid arthritis. Neither Dr. Gabriel nor any of the other coinvestigators reported any financial disclosures.

SAN FRANCISCO — An unexpected, significant uptick in rheumatoid arthritis incidence among women may point to increased exposure to hormonal and environmental risk factors, although investigators remain unsure of a clear explanation.

“What we had seen over the last 50 years was a continuous decline [in RA incidence] from the 1950s to the [mid] 1990s,” Dr. Hilal Maradit Kremers said during a press briefing at the annual meeting of the American College of Rheumatology. “We were expecting that decline to continue.”

Surprisingly, the trend instead reversed quite dramatically between 1995 and 2004, according to what began as a rather routine update of incidence trends in Olmsted County, Minn., by Dr. Maradit Kremers and her associates at the Mayo Clinic, Rochester, Minn.

The age-adjusted incidence in women was 54 per 100,000 in the post-1995 analysis, compared with 36.4 per 100,000 between 1985 and 2004.

The average age of onset for women was 56.5 years, roughly the same as in previous years.

Among men, the incidence of RA remained steady between 1995 and 2004, at 28.6 per 100,000, compared with previous decades.

Although the Midwestern population included in long-term Mayo Clinic epidemiologic studies underrepresents nonwhite populations, it has the advantage of stability, allowing disease trends to be detected quite accurately. So Dr. Maradit Kremers could say with considerable confidence that “the incidence of this disease is rising again.”

What remains a mystery is why the incidence rate would change, and so rapidly. “This was purely an observational study,” she said. “At this point we can only speculate that some [unknown] risk factors may be operating to increase the occurrence of this disease.”

Smoking, the most well-established risk factor for the development of RA, actually declined among women in the United States between 1990 and 2003, from 23% of women to 19%, according to statistics from the Centers for Disease Control and Prevention.

Obesity, which did escalate during the years of the study, is not generally associated with development of RA, said Dr. Maradit Kremers, a clinical epidemiologist.

Genetics, hormones, diet, and viral exposure have all been proposed as potential risk factors for RA (Scand. J. Rheumatol. 2006;35:169–74).

Since cases in women appear to be driving the recent surge in incidence, hormonal and reproductive factors will undoubtedly be the focus of new scrutiny, she said.

Some 20 studies have explored such risk factors over the years, generally pointing to pregnancy and oral contraceptive use as protective.

The respective roles of childbearing age, total number of children, breast-feeding, and use of hormone therapy are as yet unclear, she said.

Dr. Maradit Kremers said the study has “important implications” for policy makers, especially with regard to resource allocation for a disease suddenly on the rise after years of decline.

“This worrisome increase in occurrence of RA not only offers us clues into the causes of RA, but also highlights the need for more research into the causes and treatment of this devastating disease,” Dr. Sherine Gabriel, a Mayo Clinic rheumatologist and lead author of the study, said in a statement.

Dr. Maradit Kremers disclosed that she has received research grants and/or consultant fees from Pfizer Inc. and Amgen Inc., makers of drugs prescribed for rheumatoid arthritis. Neither Dr. Gabriel nor any of the other coinvestigators reported any financial disclosures.

SAN FRANCISCO — An unexpected, significant uptick in rheumatoid arthritis incidence among women may point to increased exposure to hormonal and environmental risk factors, although investigators remain unsure of a clear explanation.

“What we had seen over the last 50 years was a continuous decline [in RA incidence] from the 1950s to the [mid] 1990s,” Dr. Hilal Maradit Kremers said during a press briefing at the annual meeting of the American College of Rheumatology. “We were expecting that decline to continue.”

Surprisingly, the trend instead reversed quite dramatically between 1995 and 2004, according to what began as a rather routine update of incidence trends in Olmsted County, Minn., by Dr. Maradit Kremers and her associates at the Mayo Clinic, Rochester, Minn.

The age-adjusted incidence in women was 54 per 100,000 in the post-1995 analysis, compared with 36.4 per 100,000 between 1985 and 2004.

The average age of onset for women was 56.5 years, roughly the same as in previous years.

Among men, the incidence of RA remained steady between 1995 and 2004, at 28.6 per 100,000, compared with previous decades.

Although the Midwestern population included in long-term Mayo Clinic epidemiologic studies underrepresents nonwhite populations, it has the advantage of stability, allowing disease trends to be detected quite accurately. So Dr. Maradit Kremers could say with considerable confidence that “the incidence of this disease is rising again.”

What remains a mystery is why the incidence rate would change, and so rapidly. “This was purely an observational study,” she said. “At this point we can only speculate that some [unknown] risk factors may be operating to increase the occurrence of this disease.”

Smoking, the most well-established risk factor for the development of RA, actually declined among women in the United States between 1990 and 2003, from 23% of women to 19%, according to statistics from the Centers for Disease Control and Prevention.

Obesity, which did escalate during the years of the study, is not generally associated with development of RA, said Dr. Maradit Kremers, a clinical epidemiologist.

Genetics, hormones, diet, and viral exposure have all been proposed as potential risk factors for RA (Scand. J. Rheumatol. 2006;35:169–74).

Since cases in women appear to be driving the recent surge in incidence, hormonal and reproductive factors will undoubtedly be the focus of new scrutiny, she said.

Some 20 studies have explored such risk factors over the years, generally pointing to pregnancy and oral contraceptive use as protective.

The respective roles of childbearing age, total number of children, breast-feeding, and use of hormone therapy are as yet unclear, she said.

Dr. Maradit Kremers said the study has “important implications” for policy makers, especially with regard to resource allocation for a disease suddenly on the rise after years of decline.

“This worrisome increase in occurrence of RA not only offers us clues into the causes of RA, but also highlights the need for more research into the causes and treatment of this devastating disease,” Dr. Sherine Gabriel, a Mayo Clinic rheumatologist and lead author of the study, said in a statement.

Dr. Maradit Kremers disclosed that she has received research grants and/or consultant fees from Pfizer Inc. and Amgen Inc., makers of drugs prescribed for rheumatoid arthritis. Neither Dr. Gabriel nor any of the other coinvestigators reported any financial disclosures.

The Food and Drug Administration has approved an injectable gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of advanced prostate cancer. It is the first new agent cleared to treat the disease since 2004.

Degarelix, which will launch in Europe in early 2009 under the name Firmagon, was shown in phase III trials to outpace leuprolide (Lupron) in rapidly suppressing testosterone, without the androgen flare associated with Lupron and other luteinizing hormone-releasing hormone (LHRH) agonists.

Potential trade names for the new drug in the United States are still being reviewed with the FDA, according to a statement issued by Parsippany, N.J.-based Ferring Pharmaceuticals USA following the approval late last year. After those discussions are complete, an immediate commercial release of the drug is planned.

The drug offers a new spin on hormone treatment for advanced prostate cancer, directly binding to GnRH receptors on pituitary cells, rather than working more circuitously, through hypothalamic downregulation of LH secretion, like LHRH agonists.

The more direct route achieves very rapid and sustained testosterone suppression, clinical trial data confirmed.

In a 12-month, randomized, open-label phase III study of 610 patients, testosterone was suppressed to 0.5 ng/mL or less within 3 days in 96.1% and 95.5% of patients receiving either of two dosing regimens of degarelix and no patients in the comparative leuprolide group (BJU Int. 2008;102:1531–8).

By day 14 of the study, castrate levels of testosterone were demonstrated in 99% of degarelix patients compared with 18% receiving leuprolide.

“Use of a GnRH receptor antagonist is a highly efficient way to stop the production of testosterone,” Dr. Neal Shore, medical director of the Carolina Urologic Research Center, Myrtle Beach, S.C., said in the statement.

“The approval of degarelix offers the medical community an effective alternative in the treatment of hormonally sensitive prostate cancer,” said Dr. Shore, a clinical trial investigator and advisor to Ferring.

One potential advantage of degarelix over LHRH agonists is the avoidance of early stimulation of hormone receptors during LH downregulation. Antiandrogen therapy is required to prevent this brief testosterone “surge,” and subsequent tumor growth, the FDA said.

The most frequent adverse events seen in clinical trials of degarelix were injection site reactions, including pain, redness, and swelling; hot flashes; increased weight; fatigue; and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Reactions were rated as grade 1 or 2 (mild to moderate) in 99% of patients.

The approved dosage for degarelix is initially 240 mg given in equal, divided injections, followed by monthly single injections of 80 mg.

Degarelix had a much less tumultuous journey through the FDA approval process than did Provenge, an experimental immunotherapeutic agent that received a recommendation from an FDA panel in March. The agency withheld approval in May, requesting more efficacy data. Supplemental trial data should be complete in 2009, with approval possible in the second half of the year. The panel and the agency agreed on approval of degarelix based on phase III trial data.

“There is an ongoing need for additional treatment options for these patients,” Dr. Richard Pazdur, director of the FDA's Office of Oncology Drug Products, Center for Drug Evaluation and Research, said in a statement.

The Food and Drug Administration has approved an injectable gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of advanced prostate cancer. It is the first new agent cleared to treat the disease since 2004.

Degarelix, which will launch in Europe in early 2009 under the name Firmagon, was shown in phase III trials to outpace leuprolide (Lupron) in rapidly suppressing testosterone, without the androgen flare associated with Lupron and other luteinizing hormone-releasing hormone (LHRH) agonists.

Potential trade names for the new drug in the United States are still being reviewed with the FDA, according to a statement issued by Parsippany, N.J.-based Ferring Pharmaceuticals USA following the approval late last year. After those discussions are complete, an immediate commercial release of the drug is planned.

The drug offers a new spin on hormone treatment for advanced prostate cancer, directly binding to GnRH receptors on pituitary cells, rather than working more circuitously, through hypothalamic downregulation of LH secretion, like LHRH agonists.

The more direct route achieves very rapid and sustained testosterone suppression, clinical trial data confirmed.

In a 12-month, randomized, open-label phase III study of 610 patients, testosterone was suppressed to 0.5 ng/mL or less within 3 days in 96.1% and 95.5% of patients receiving either of two dosing regimens of degarelix and no patients in the comparative leuprolide group (BJU Int. 2008;102:1531–8).

By day 14 of the study, castrate levels of testosterone were demonstrated in 99% of degarelix patients compared with 18% receiving leuprolide.

“Use of a GnRH receptor antagonist is a highly efficient way to stop the production of testosterone,” Dr. Neal Shore, medical director of the Carolina Urologic Research Center, Myrtle Beach, S.C., said in the statement.

“The approval of degarelix offers the medical community an effective alternative in the treatment of hormonally sensitive prostate cancer,” said Dr. Shore, a clinical trial investigator and advisor to Ferring.

One potential advantage of degarelix over LHRH agonists is the avoidance of early stimulation of hormone receptors during LH downregulation. Antiandrogen therapy is required to prevent this brief testosterone “surge,” and subsequent tumor growth, the FDA said.

The most frequent adverse events seen in clinical trials of degarelix were injection site reactions, including pain, redness, and swelling; hot flashes; increased weight; fatigue; and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Reactions were rated as grade 1 or 2 (mild to moderate) in 99% of patients.

The approved dosage for degarelix is initially 240 mg given in equal, divided injections, followed by monthly single injections of 80 mg.

Degarelix had a much less tumultuous journey through the FDA approval process than did Provenge, an experimental immunotherapeutic agent that received a recommendation from an FDA panel in March. The agency withheld approval in May, requesting more efficacy data. Supplemental trial data should be complete in 2009, with approval possible in the second half of the year. The panel and the agency agreed on approval of degarelix based on phase III trial data.

“There is an ongoing need for additional treatment options for these patients,” Dr. Richard Pazdur, director of the FDA's Office of Oncology Drug Products, Center for Drug Evaluation and Research, said in a statement.

The Food and Drug Administration has approved an injectable gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of advanced prostate cancer. It is the first new agent cleared to treat the disease since 2004.

Degarelix, which will launch in Europe in early 2009 under the name Firmagon, was shown in phase III trials to outpace leuprolide (Lupron) in rapidly suppressing testosterone, without the androgen flare associated with Lupron and other luteinizing hormone-releasing hormone (LHRH) agonists.

Potential trade names for the new drug in the United States are still being reviewed with the FDA, according to a statement issued by Parsippany, N.J.-based Ferring Pharmaceuticals USA following the approval late last year. After those discussions are complete, an immediate commercial release of the drug is planned.

The drug offers a new spin on hormone treatment for advanced prostate cancer, directly binding to GnRH receptors on pituitary cells, rather than working more circuitously, through hypothalamic downregulation of LH secretion, like LHRH agonists.

The more direct route achieves very rapid and sustained testosterone suppression, clinical trial data confirmed.

In a 12-month, randomized, open-label phase III study of 610 patients, testosterone was suppressed to 0.5 ng/mL or less within 3 days in 96.1% and 95.5% of patients receiving either of two dosing regimens of degarelix and no patients in the comparative leuprolide group (BJU Int. 2008;102:1531–8).

By day 14 of the study, castrate levels of testosterone were demonstrated in 99% of degarelix patients compared with 18% receiving leuprolide.

“Use of a GnRH receptor antagonist is a highly efficient way to stop the production of testosterone,” Dr. Neal Shore, medical director of the Carolina Urologic Research Center, Myrtle Beach, S.C., said in the statement.

“The approval of degarelix offers the medical community an effective alternative in the treatment of hormonally sensitive prostate cancer,” said Dr. Shore, a clinical trial investigator and advisor to Ferring.

One potential advantage of degarelix over LHRH agonists is the avoidance of early stimulation of hormone receptors during LH downregulation. Antiandrogen therapy is required to prevent this brief testosterone “surge,” and subsequent tumor growth, the FDA said.

The most frequent adverse events seen in clinical trials of degarelix were injection site reactions, including pain, redness, and swelling; hot flashes; increased weight; fatigue; and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Reactions were rated as grade 1 or 2 (mild to moderate) in 99% of patients.

The approved dosage for degarelix is initially 240 mg given in equal, divided injections, followed by monthly single injections of 80 mg.

Degarelix had a much less tumultuous journey through the FDA approval process than did Provenge, an experimental immunotherapeutic agent that received a recommendation from an FDA panel in March. The agency withheld approval in May, requesting more efficacy data. Supplemental trial data should be complete in 2009, with approval possible in the second half of the year. The panel and the agency agreed on approval of degarelix based on phase III trial data.

“There is an ongoing need for additional treatment options for these patients,” Dr. Richard Pazdur, director of the FDA's Office of Oncology Drug Products, Center for Drug Evaluation and Research, said in a statement.

The Food and Drug Administration has directed physicians to inform patients taking anticonvulsant medications that the drugs have the potential to increase suicidal thoughts and behavior.

Families and caregivers should also be notified of this risk so that they can be attuned to changes in behavior in patients receiving the medications, according to the FDA's alert for health care professionals.

Based on an agency review of nearly 200 clinical trials of 11 antiepileptic drugs, the directive coincided with an FDA announcement that manufacturers of any medication in the class will be required to add warnings about suicidal thoughts or behavior in prescribing information or labeling and to develop medication guides for patients.

Revised labeling or an explanation “why they do not believe such labeling changes are necessary” must be submitted to the agency within 30 days.

Jack Cox, a spokesman for Pfizer Inc., said in a telephone interview his firm will comply with the order.

“Pfizer will work closely with the FDA to update the labeling of our antiepileptic medications Lyrica [pregabalin] and Neurontin [gabapentin], in a timely manner,” he said.

“We have not heard directly from the FDA, but we will work to address any of the agency's concerns,” said Tricia Geoghegan, a spokesperson for Ortho-McNeil Neurologics, makers of topiramate.

Ms. Geoghegan noted that the label for Topamax (topiramate) has always included “content about this topic,” but added that revisions will be made should the FDA request them.

The agency's decision drew on data from placebo-controlled clinical trials that enrolled 43,892 patients aged 5 years and older taking the medications for epilepsy, psychiatric disorders, and other conditions.

The FDA meta-analytic review of 199 trials determined that patients receiving antiepileptic drugs were at a twofold risk of suicidal behavior or thoughts (0.43%), compared with patients receiving placebo (0.24%).

The difference translates to 1 additional case of suicidality per 530 patients treated with antiepileptic drugs.

The absolute rate of events was highest in psychiatric patients (8.5 suicidality reports per 1,000 patients who were receiving antiepileptic medications, compared with 5.7 per 1,000 for psychiatric patients who were taking placebo).

Among epilepsy patients, 3.4 events per 1,000 were reported for those receiving antiepileptic medications, compared with 1.0 for those assigned to receive placebo.

The FDA's health care alert is available at www.fda.gov/cder/drug/InfoSheets/HCP/antiepileptics200812.htm

The Food and Drug Administration has directed physicians to inform patients taking anticonvulsant medications that the drugs have the potential to increase suicidal thoughts and behavior.

Families and caregivers should also be notified of this risk so that they can be attuned to changes in behavior in patients receiving the medications, according to the FDA's alert for health care professionals.

Based on an agency review of nearly 200 clinical trials of 11 antiepileptic drugs, the directive coincided with an FDA announcement that manufacturers of any medication in the class will be required to add warnings about suicidal thoughts or behavior in prescribing information or labeling and to develop medication guides for patients.

Revised labeling or an explanation “why they do not believe such labeling changes are necessary” must be submitted to the agency within 30 days.

Jack Cox, a spokesman for Pfizer Inc., said in a telephone interview his firm will comply with the order.

“Pfizer will work closely with the FDA to update the labeling of our antiepileptic medications Lyrica [pregabalin] and Neurontin [gabapentin], in a timely manner,” he said.

“We have not heard directly from the FDA, but we will work to address any of the agency's concerns,” said Tricia Geoghegan, a spokesperson for Ortho-McNeil Neurologics, makers of topiramate.

Ms. Geoghegan noted that the label for Topamax (topiramate) has always included “content about this topic,” but added that revisions will be made should the FDA request them.

The agency's decision drew on data from placebo-controlled clinical trials that enrolled 43,892 patients aged 5 years and older taking the medications for epilepsy, psychiatric disorders, and other conditions.

The FDA meta-analytic review of 199 trials determined that patients receiving antiepileptic drugs were at a twofold risk of suicidal behavior or thoughts (0.43%), compared with patients receiving placebo (0.24%).

The difference translates to 1 additional case of suicidality per 530 patients treated with antiepileptic drugs.

The absolute rate of events was highest in psychiatric patients (8.5 suicidality reports per 1,000 patients who were receiving antiepileptic medications, compared with 5.7 per 1,000 for psychiatric patients who were taking placebo).

Among epilepsy patients, 3.4 events per 1,000 were reported for those receiving antiepileptic medications, compared with 1.0 for those assigned to receive placebo.

The FDA's health care alert is available at www.fda.gov/cder/drug/InfoSheets/HCP/antiepileptics200812.htm

The Food and Drug Administration has directed physicians to inform patients taking anticonvulsant medications that the drugs have the potential to increase suicidal thoughts and behavior.

Families and caregivers should also be notified of this risk so that they can be attuned to changes in behavior in patients receiving the medications, according to the FDA's alert for health care professionals.

Based on an agency review of nearly 200 clinical trials of 11 antiepileptic drugs, the directive coincided with an FDA announcement that manufacturers of any medication in the class will be required to add warnings about suicidal thoughts or behavior in prescribing information or labeling and to develop medication guides for patients.

Revised labeling or an explanation “why they do not believe such labeling changes are necessary” must be submitted to the agency within 30 days.

Jack Cox, a spokesman for Pfizer Inc., said in a telephone interview his firm will comply with the order.

“Pfizer will work closely with the FDA to update the labeling of our antiepileptic medications Lyrica [pregabalin] and Neurontin [gabapentin], in a timely manner,” he said.

“We have not heard directly from the FDA, but we will work to address any of the agency's concerns,” said Tricia Geoghegan, a spokesperson for Ortho-McNeil Neurologics, makers of topiramate.

Ms. Geoghegan noted that the label for Topamax (topiramate) has always included “content about this topic,” but added that revisions will be made should the FDA request them.

The agency's decision drew on data from placebo-controlled clinical trials that enrolled 43,892 patients aged 5 years and older taking the medications for epilepsy, psychiatric disorders, and other conditions.

The FDA meta-analytic review of 199 trials determined that patients receiving antiepileptic drugs were at a twofold risk of suicidal behavior or thoughts (0.43%), compared with patients receiving placebo (0.24%).

The difference translates to 1 additional case of suicidality per 530 patients treated with antiepileptic drugs.

The absolute rate of events was highest in psychiatric patients (8.5 suicidality reports per 1,000 patients who were receiving antiepileptic medications, compared with 5.7 per 1,000 for psychiatric patients who were taking placebo).

Among epilepsy patients, 3.4 events per 1,000 were reported for those receiving antiepileptic medications, compared with 1.0 for those assigned to receive placebo.

The FDA's health care alert is available at www.fda.gov/cder/drug/InfoSheets/HCP/antiepileptics200812.htm

LAS VEGAS — As a pediatric dermatologist, Dr. Fred Ghali is often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, so he relishes being able to say to a family: “No worries.”

Such is the case with three common but sometimes unrecognized diagnoses presenting to his practice in Grapevine, Tex. He spoke about the following conditions at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Pseudo acne. Most parents recognize children are maturing earlier these days, but they still panic when they see what they think is acne developing in their 5- or 6-year-old. The white papules on a young child's nose are likely “pseudo acne,” small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature epidermal cysts rupture, they may take on an inflammatory appearance resembling acne. Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary.

▸ Striking striae. These deep, dark, horizontal marks lining the back of 13- or 14-year-old boys, usually “[white] children who are extremely skinny,” appear as welt-like striations. Dr. Ghali first theorized that the bands of discoloration might be caused by carrying heavy backpacks or doing wacky skateboard maneuvers. However, adolescents with this condition “have lots of vertical growth over a short period of time,” he said. The striae tend to fade over time and resolve far better than striae of pregnancy. No treatment is needed.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans, but in a child of normal weight, with no other signs of metabolic illness, this condition is easily dispensed with. “Just walk in with a little bit of alcohol and wipe it off. You can look like a hero,” said Dr. Ghali. The condition is common in young children.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

LAS VEGAS — As a pediatric dermatologist, Dr. Fred Ghali is often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, so he relishes being able to say to a family: “No worries.”

Such is the case with three common but sometimes unrecognized diagnoses presenting to his practice in Grapevine, Tex. He spoke about the following conditions at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Pseudo acne. Most parents recognize children are maturing earlier these days, but they still panic when they see what they think is acne developing in their 5- or 6-year-old. The white papules on a young child's nose are likely “pseudo acne,” small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature epidermal cysts rupture, they may take on an inflammatory appearance resembling acne. Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary.

▸ Striking striae. These deep, dark, horizontal marks lining the back of 13- or 14-year-old boys, usually “[white] children who are extremely skinny,” appear as welt-like striations. Dr. Ghali first theorized that the bands of discoloration might be caused by carrying heavy backpacks or doing wacky skateboard maneuvers. However, adolescents with this condition “have lots of vertical growth over a short period of time,” he said. The striae tend to fade over time and resolve far better than striae of pregnancy. No treatment is needed.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans, but in a child of normal weight, with no other signs of metabolic illness, this condition is easily dispensed with. “Just walk in with a little bit of alcohol and wipe it off. You can look like a hero,” said Dr. Ghali. The condition is common in young children.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

LAS VEGAS — As a pediatric dermatologist, Dr. Fred Ghali is often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, so he relishes being able to say to a family: “No worries.”

Such is the case with three common but sometimes unrecognized diagnoses presenting to his practice in Grapevine, Tex. He spoke about the following conditions at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Pseudo acne. Most parents recognize children are maturing earlier these days, but they still panic when they see what they think is acne developing in their 5- or 6-year-old. The white papules on a young child's nose are likely “pseudo acne,” small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature epidermal cysts rupture, they may take on an inflammatory appearance resembling acne. Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary.

▸ Striking striae. These deep, dark, horizontal marks lining the back of 13- or 14-year-old boys, usually “[white] children who are extremely skinny,” appear as welt-like striations. Dr. Ghali first theorized that the bands of discoloration might be caused by carrying heavy backpacks or doing wacky skateboard maneuvers. However, adolescents with this condition “have lots of vertical growth over a short period of time,” he said. The striae tend to fade over time and resolve far better than striae of pregnancy. No treatment is needed.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans, but in a child of normal weight, with no other signs of metabolic illness, this condition is easily dispensed with. “Just walk in with a little bit of alcohol and wipe it off. You can look like a hero,” said Dr. Ghali. The condition is common in young children.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities.

Natural light reveals hair the color of lead and with a “peculiar” shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, Dr. Carola Durán-McKinster said at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, found the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Gris-celli syndrome, and 8 of 10 with traditional Elejalde syndrome. Four children who did not fit diagnostic criteria for any systemic syndrome survived.

Children with silvery hair syndromes have skin that is so hypo-pigmented at birth they may resemble children with albinism, though after exposure to sunlight, their skin becomes deeply, bronzed, said Dr. Durán-McKinster, who is on the dermatology faculty at Universidad Nacional Autónoma de México. Careful examination of an infants' hair is critical to making a diagnosis, often with important prognostic and treatment implications.

A decrease or total loss of hair or skin color can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melano-cytes and transferred to neighboring keratinocytes. Gene mutations that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two silvery hair syndromes, Elejalde and Griscelli, respectively.

Dermatologists may readily recognize the light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is less common and should be investigated with light microscopy and a biopsy. Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain.

Light microscopy of the hair shaft can show a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome, in which small clumps of melanin are evenly distributed in contrast to the irregular spread of giant and small melanin clumps in Elejalde.

A prompt and accurate diagnosis can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest. SDEF and this news organization are wholly owned subsidiaries of Elsevier.

Root Cause May Involve One of Four Diagnoses

Dr. Durán-McKinster described the following silvery hair syndromes:

▸ Chédiak-Higasi. In this rare, autosomal recessive disorder, giant inclusion bodies are found in granule-containing cells. Children are immunocompromised. Lymphocytes and histiocytes accumulate in the liver, spleen, lymph nodes, and bone marrow, causing hepatosplenomegaly, bone marrow infiltration, bleeding, and hemophagocytosis. High doses of methylprednisolone and splenectomy may help; allogeneic bone marrow transplantation is done when possible.

▸ Griscelli syndrome. Children with this severe, autosomal recessive immunodeficiency syndrome can develop hemophagocytic syndrome, with infectious episodes, and pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Treatment of choice is allogeneic bone marrow transplantation.

▸ Elejalde syndrome. This is also an autosomal recessive disease with severe neurologic abnormalities, including hypotonia, mental retardation, and progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomescan also occur.

▸ Silvery hair without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin have silvery hair and bronzed skin after sun exposure, but do not exhibit immunologic or neurologic complications.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities.

Natural light reveals hair the color of lead and with a “peculiar” shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, Dr. Carola Durán-McKinster said at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, found the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Gris-celli syndrome, and 8 of 10 with traditional Elejalde syndrome. Four children who did not fit diagnostic criteria for any systemic syndrome survived.

Children with silvery hair syndromes have skin that is so hypo-pigmented at birth they may resemble children with albinism, though after exposure to sunlight, their skin becomes deeply, bronzed, said Dr. Durán-McKinster, who is on the dermatology faculty at Universidad Nacional Autónoma de México. Careful examination of an infants' hair is critical to making a diagnosis, often with important prognostic and treatment implications.

A decrease or total loss of hair or skin color can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melano-cytes and transferred to neighboring keratinocytes. Gene mutations that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two silvery hair syndromes, Elejalde and Griscelli, respectively.

Dermatologists may readily recognize the light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is less common and should be investigated with light microscopy and a biopsy. Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain.

Light microscopy of the hair shaft can show a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome, in which small clumps of melanin are evenly distributed in contrast to the irregular spread of giant and small melanin clumps in Elejalde.

A prompt and accurate diagnosis can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest. SDEF and this news organization are wholly owned subsidiaries of Elsevier.

Root Cause May Involve One of Four Diagnoses

Dr. Durán-McKinster described the following silvery hair syndromes:

▸ Chédiak-Higasi. In this rare, autosomal recessive disorder, giant inclusion bodies are found in granule-containing cells. Children are immunocompromised. Lymphocytes and histiocytes accumulate in the liver, spleen, lymph nodes, and bone marrow, causing hepatosplenomegaly, bone marrow infiltration, bleeding, and hemophagocytosis. High doses of methylprednisolone and splenectomy may help; allogeneic bone marrow transplantation is done when possible.

▸ Griscelli syndrome. Children with this severe, autosomal recessive immunodeficiency syndrome can develop hemophagocytic syndrome, with infectious episodes, and pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Treatment of choice is allogeneic bone marrow transplantation.

▸ Elejalde syndrome. This is also an autosomal recessive disease with severe neurologic abnormalities, including hypotonia, mental retardation, and progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomescan also occur.

▸ Silvery hair without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin have silvery hair and bronzed skin after sun exposure, but do not exhibit immunologic or neurologic complications.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities.

Natural light reveals hair the color of lead and with a “peculiar” shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, Dr. Carola Durán-McKinster said at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, found the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Gris-celli syndrome, and 8 of 10 with traditional Elejalde syndrome. Four children who did not fit diagnostic criteria for any systemic syndrome survived.

Children with silvery hair syndromes have skin that is so hypo-pigmented at birth they may resemble children with albinism, though after exposure to sunlight, their skin becomes deeply, bronzed, said Dr. Durán-McKinster, who is on the dermatology faculty at Universidad Nacional Autónoma de México. Careful examination of an infants' hair is critical to making a diagnosis, often with important prognostic and treatment implications.

A decrease or total loss of hair or skin color can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melano-cytes and transferred to neighboring keratinocytes. Gene mutations that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two silvery hair syndromes, Elejalde and Griscelli, respectively.

Dermatologists may readily recognize the light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is less common and should be investigated with light microscopy and a biopsy. Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain.

Light microscopy of the hair shaft can show a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome, in which small clumps of melanin are evenly distributed in contrast to the irregular spread of giant and small melanin clumps in Elejalde.

A prompt and accurate diagnosis can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest. SDEF and this news organization are wholly owned subsidiaries of Elsevier.

Root Cause May Involve One of Four Diagnoses

Dr. Durán-McKinster described the following silvery hair syndromes:

▸ Chédiak-Higasi. In this rare, autosomal recessive disorder, giant inclusion bodies are found in granule-containing cells. Children are immunocompromised. Lymphocytes and histiocytes accumulate in the liver, spleen, lymph nodes, and bone marrow, causing hepatosplenomegaly, bone marrow infiltration, bleeding, and hemophagocytosis. High doses of methylprednisolone and splenectomy may help; allogeneic bone marrow transplantation is done when possible.

▸ Griscelli syndrome. Children with this severe, autosomal recessive immunodeficiency syndrome can develop hemophagocytic syndrome, with infectious episodes, and pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Treatment of choice is allogeneic bone marrow transplantation.

▸ Elejalde syndrome. This is also an autosomal recessive disease with severe neurologic abnormalities, including hypotonia, mental retardation, and progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomescan also occur.

▸ Silvery hair without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin have silvery hair and bronzed skin after sun exposure, but do not exhibit immunologic or neurologic complications.

LAS VEGAS — An evolving understanding of the pathogenesis of calciphylaxis in hospitalized patients may lead to antithrombotic treatment strategies focused on vascular occlusion as well as dialysis- and parathyroid-specific interventions.

“Calciphylaxis is a therapeutic conundrum and also a nightmare,” said Dr. Mark D.P. Davis, professor of dermatology at the Mayo Clinic, Rochester, Minn.

“We urgently need better treatment and preventive strategies,” he stressed at a dermatology seminar sponsored by Skin Disease Education Foundation.

The condition's name, calciphylaxis, reflects an early belief that the introduction of a certain agent (likely during dialysis) induced calcification of vessels, a notion now disputed since the disease occurs in patients without renal insufficiency.

A more accurate name, first proposed by Dr. Patrick Dahl and associates, is the vascular calcification-cutaneous necrosis syndrome (J. Am. Acad. Dermatol. 1995;33:53–8), which better characterizes calciphylaxis as “akin to a myocardial infarction,” Dr. Davis said.

Calcifications in the walls of small arterioles supplying the skin are the first evidence of the disorder. The resultant clots then trigger skin infarctions, just as a blockage of a vessel leads to a myocardial infarction.

Treatment strategies at Mayo focus on vascular occlusion, along with management of hypercalcemia (with low calcium dialysate and sodium thiosulfate in dialysis patients), hyperphosphatemia (with phosphate binding agents), hyperparathyroidism (with cinacalcet and bisphosphonates), and pain.

“We … feel it's very important to treat vascular occlusions and eliminate these luminal thromboses causing this cutaneous infarct,” he said. “One way to treat an existing clot is to use thrombolytic agents.”

Several Mayo Clinic patients have been treated in this fashion with infused tissue plasminogen activator (tPA) at doses 1/10 of those used to treat a myocardial infarction. Because of concern over bleeding, patients are admitted for the 2-week procedure, he said.

“We have had some success and are presently reviewing our experience with this approach,” Dr. Davis said.

Anticoagulant medications, including heparin, low-molecular-weight heparin, and warfarin, are also used in calciphylaxis patients “so they don't further clot.”

Dr. M.R. (Pete) Hayden, a calciphylaxis researcher who has published several studies on sodium thiosulfate as a possible treatment for calciphylaxis, said in an e-mail message that he is “looking forward excitedly to future papers” on the anticoagulant approach from Dr. Davis and Mayo researchers.

“Indeed, thrombolytic agents may be an important adjunctive intervention along with calcium-chelating agents and phosphate binding agents in appropriate patients because there are so many precipitating variables important to the development of calciphylaxis,” wrote Dr. Hayden, research professor of internal medicine in the division of endocrinology, diabetes, and metabolism at the University of Missouri, Camdenton campus.

Other interventions have not fared as well. A comprehensive review of 64 patients treated at the Mayo Clinic failed to find any survival benefit for parathyroidectomy, despite case studies and series suggesting the surgery is beneficial (J. Am. Acad. Dermatol. 2007;57:365–6).

Debridement was associated with a 1-year survival rate of 62%, compared with 27% survival rates in patients who failed to undergo the procedure. Because surgical and mechanical debridement are difficult to perform in patients with this “excruciatingly painful” disease, painless debridement using maggots and ultrasound is being utilized at Mayo to good effect, Dr. Davis said.

A population-based study conducted in the Rochester, Minn., area found an incidence of 4.5 cases per million people, per year. About 1% of patients with chronic renal failure and 4% of dialysis patients reportedly have the disease.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS — An evolving understanding of the pathogenesis of calciphylaxis in hospitalized patients may lead to antithrombotic treatment strategies focused on vascular occlusion as well as dialysis- and parathyroid-specific interventions.

“Calciphylaxis is a therapeutic conundrum and also a nightmare,” said Dr. Mark D.P. Davis, professor of dermatology at the Mayo Clinic, Rochester, Minn.

“We urgently need better treatment and preventive strategies,” he stressed at a dermatology seminar sponsored by Skin Disease Education Foundation.

The condition's name, calciphylaxis, reflects an early belief that the introduction of a certain agent (likely during dialysis) induced calcification of vessels, a notion now disputed since the disease occurs in patients without renal insufficiency.

A more accurate name, first proposed by Dr. Patrick Dahl and associates, is the vascular calcification-cutaneous necrosis syndrome (J. Am. Acad. Dermatol. 1995;33:53–8), which better characterizes calciphylaxis as “akin to a myocardial infarction,” Dr. Davis said.

Calcifications in the walls of small arterioles supplying the skin are the first evidence of the disorder. The resultant clots then trigger skin infarctions, just as a blockage of a vessel leads to a myocardial infarction.

Treatment strategies at Mayo focus on vascular occlusion, along with management of hypercalcemia (with low calcium dialysate and sodium thiosulfate in dialysis patients), hyperphosphatemia (with phosphate binding agents), hyperparathyroidism (with cinacalcet and bisphosphonates), and pain.

“We … feel it's very important to treat vascular occlusions and eliminate these luminal thromboses causing this cutaneous infarct,” he said. “One way to treat an existing clot is to use thrombolytic agents.”

Several Mayo Clinic patients have been treated in this fashion with infused tissue plasminogen activator (tPA) at doses 1/10 of those used to treat a myocardial infarction. Because of concern over bleeding, patients are admitted for the 2-week procedure, he said.

“We have had some success and are presently reviewing our experience with this approach,” Dr. Davis said.

Anticoagulant medications, including heparin, low-molecular-weight heparin, and warfarin, are also used in calciphylaxis patients “so they don't further clot.”

Dr. M.R. (Pete) Hayden, a calciphylaxis researcher who has published several studies on sodium thiosulfate as a possible treatment for calciphylaxis, said in an e-mail message that he is “looking forward excitedly to future papers” on the anticoagulant approach from Dr. Davis and Mayo researchers.

“Indeed, thrombolytic agents may be an important adjunctive intervention along with calcium-chelating agents and phosphate binding agents in appropriate patients because there are so many precipitating variables important to the development of calciphylaxis,” wrote Dr. Hayden, research professor of internal medicine in the division of endocrinology, diabetes, and metabolism at the University of Missouri, Camdenton campus.

Other interventions have not fared as well. A comprehensive review of 64 patients treated at the Mayo Clinic failed to find any survival benefit for parathyroidectomy, despite case studies and series suggesting the surgery is beneficial (J. Am. Acad. Dermatol. 2007;57:365–6).

Debridement was associated with a 1-year survival rate of 62%, compared with 27% survival rates in patients who failed to undergo the procedure. Because surgical and mechanical debridement are difficult to perform in patients with this “excruciatingly painful” disease, painless debridement using maggots and ultrasound is being utilized at Mayo to good effect, Dr. Davis said.

A population-based study conducted in the Rochester, Minn., area found an incidence of 4.5 cases per million people, per year. About 1% of patients with chronic renal failure and 4% of dialysis patients reportedly have the disease.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS — An evolving understanding of the pathogenesis of calciphylaxis in hospitalized patients may lead to antithrombotic treatment strategies focused on vascular occlusion as well as dialysis- and parathyroid-specific interventions.

“Calciphylaxis is a therapeutic conundrum and also a nightmare,” said Dr. Mark D.P. Davis, professor of dermatology at the Mayo Clinic, Rochester, Minn.

“We urgently need better treatment and preventive strategies,” he stressed at a dermatology seminar sponsored by Skin Disease Education Foundation.

The condition's name, calciphylaxis, reflects an early belief that the introduction of a certain agent (likely during dialysis) induced calcification of vessels, a notion now disputed since the disease occurs in patients without renal insufficiency.

A more accurate name, first proposed by Dr. Patrick Dahl and associates, is the vascular calcification-cutaneous necrosis syndrome (J. Am. Acad. Dermatol. 1995;33:53–8), which better characterizes calciphylaxis as “akin to a myocardial infarction,” Dr. Davis said.

Calcifications in the walls of small arterioles supplying the skin are the first evidence of the disorder. The resultant clots then trigger skin infarctions, just as a blockage of a vessel leads to a myocardial infarction.

Treatment strategies at Mayo focus on vascular occlusion, along with management of hypercalcemia (with low calcium dialysate and sodium thiosulfate in dialysis patients), hyperphosphatemia (with phosphate binding agents), hyperparathyroidism (with cinacalcet and bisphosphonates), and pain.

“We … feel it's very important to treat vascular occlusions and eliminate these luminal thromboses causing this cutaneous infarct,” he said. “One way to treat an existing clot is to use thrombolytic agents.”

Several Mayo Clinic patients have been treated in this fashion with infused tissue plasminogen activator (tPA) at doses 1/10 of those used to treat a myocardial infarction. Because of concern over bleeding, patients are admitted for the 2-week procedure, he said.

“We have had some success and are presently reviewing our experience with this approach,” Dr. Davis said.

Anticoagulant medications, including heparin, low-molecular-weight heparin, and warfarin, are also used in calciphylaxis patients “so they don't further clot.”

Dr. M.R. (Pete) Hayden, a calciphylaxis researcher who has published several studies on sodium thiosulfate as a possible treatment for calciphylaxis, said in an e-mail message that he is “looking forward excitedly to future papers” on the anticoagulant approach from Dr. Davis and Mayo researchers.

“Indeed, thrombolytic agents may be an important adjunctive intervention along with calcium-chelating agents and phosphate binding agents in appropriate patients because there are so many precipitating variables important to the development of calciphylaxis,” wrote Dr. Hayden, research professor of internal medicine in the division of endocrinology, diabetes, and metabolism at the University of Missouri, Camdenton campus.

Other interventions have not fared as well. A comprehensive review of 64 patients treated at the Mayo Clinic failed to find any survival benefit for parathyroidectomy, despite case studies and series suggesting the surgery is beneficial (J. Am. Acad. Dermatol. 2007;57:365–6).

Debridement was associated with a 1-year survival rate of 62%, compared with 27% survival rates in patients who failed to undergo the procedure. Because surgical and mechanical debridement are difficult to perform in patients with this “excruciatingly painful” disease, painless debridement using maggots and ultrasound is being utilized at Mayo to good effect, Dr. Davis said.

A population-based study conducted in the Rochester, Minn., area found an incidence of 4.5 cases per million people, per year. About 1% of patients with chronic renal failure and 4% of dialysis patients reportedly have the disease.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities, according to Dr. Carola Durán-McKinster.

Natural light reveals hair the color of lead that has a "peculiar" shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, said Dr. Durán-McKinster at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, determined that the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Griscelli syndrome, and 8 of 10 children with traditional Elejalde syndrome.

Four children with silvery hair who did not fit diagnostic criteria for any systemic syndrome all survived, she said.

Children with silvery hair syndromes have skin that is so hypopigmented at birth that they may resemble children with albinism.

However, after exposure to sunlight, their skin becomes deeply, persistently bronzed, explained Dr. Durán-McKinster, who serves on the dermatology faculty at Universidad Nacional Autónoma de México.

A careful examination of the hair of infants can be critical to making a diagnosis, often with important prognostic and treatment implications, she stressed.

"Hair can be a very, very good tool to making the diagnosis of genodermatoses," she said. "Pigment in the hair shaft is very special."

A decrease or total loss of color in the hair or skin can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melanocytes and transferred to neighboring keratinocytes.

Mutations in genes that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two key silvery hair syndromes, Elejalde syndrome and Griscelli syndrome, respectively, said Dr. Durán-McKinster.

Dermatologists may readily recognize the very light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is much less common, and should be investigated with light microscopy and a biopsy.

Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain, said Dr. Durán-McKinster.

Light microscopy of the hair shaft can distinguish a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome. The "very, very small clumps" of melanin are evenly distributed, in contrast to giant and small clumps of melanin distributed in an irregular pattern in Elejalde syndrome.

Clinically, the hair of a child with Elejalde syndrome may shine more brightly, since there is more space between melanin clumps to reflect light, she explained.

A prompt and accurate diagnosis of the underlying syndrome can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The Genetics of Silvery Hair

Dr. Durán-McKinster described the following syndromes:

▸ Chédiak-Higasi syndrome. In this rare, autosomal recessive disorder, giant inclusion bodies can be found in all granule-containing cells. Children are immunocompromised because of impaired phagocytosis and natural killer cell function. The genetic defect is a mutation of the LYST (lysosomal trafficking regulator) gene on chromosome 1. During an accelerated phase, lymphocytes and histiocytes can accumulate in the liver, spleen, lymph nodes, and bone marrow. High doses of methylprednisolone and splenectomy may be helpful during this phase, but allogeneic bone marrow transplantation is performed whenever possible.

▸ Griscelli syndrome. A mutation on the RAB27A gene of chromosome 15 causes this severe, autosomal recessive immunodeficiency syndrome. Many children develop hemophagocytic syndrome early, with frequent infectious episodes. Children may develop pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Delayed-type cutaneous hypersensitivity and impaired natural killer function contribute to immunodeficiency. Allogeneic bone marrow transplantation is the treatment of choice.

▸ Elejalde syndrome. This autosomal recessive disease is caused by a mutation in the gene MYO5A on chromosome 15. Severe neurologic abnormalities are seen, including hypotonia, mental retardation, and relentlessly progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomes are associated with the syndrome.

▸ Silvery hair syndrome without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin on chromosome 2 have silvery hair and bronzed skin following sun exposure; however they do not exhibit immunologic or neurologic complications.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities, according to Dr. Carola Durán-McKinster.

Natural light reveals hair the color of lead that has a "peculiar" shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, said Dr. Durán-McKinster at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, determined that the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Griscelli syndrome, and 8 of 10 children with traditional Elejalde syndrome.

Four children with silvery hair who did not fit diagnostic criteria for any systemic syndrome all survived, she said.

Children with silvery hair syndromes have skin that is so hypopigmented at birth that they may resemble children with albinism.

However, after exposure to sunlight, their skin becomes deeply, persistently bronzed, explained Dr. Durán-McKinster, who serves on the dermatology faculty at Universidad Nacional Autónoma de México.

A careful examination of the hair of infants can be critical to making a diagnosis, often with important prognostic and treatment implications, she stressed.

"Hair can be a very, very good tool to making the diagnosis of genodermatoses," she said. "Pigment in the hair shaft is very special."

A decrease or total loss of color in the hair or skin can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melanocytes and transferred to neighboring keratinocytes.

Mutations in genes that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two key silvery hair syndromes, Elejalde syndrome and Griscelli syndrome, respectively, said Dr. Durán-McKinster.

Dermatologists may readily recognize the very light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is much less common, and should be investigated with light microscopy and a biopsy.

Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain, said Dr. Durán-McKinster.

Light microscopy of the hair shaft can distinguish a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome. The "very, very small clumps" of melanin are evenly distributed, in contrast to giant and small clumps of melanin distributed in an irregular pattern in Elejalde syndrome.

Clinically, the hair of a child with Elejalde syndrome may shine more brightly, since there is more space between melanin clumps to reflect light, she explained.

A prompt and accurate diagnosis of the underlying syndrome can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The Genetics of Silvery Hair

Dr. Durán-McKinster described the following syndromes:

▸ Chédiak-Higasi syndrome. In this rare, autosomal recessive disorder, giant inclusion bodies can be found in all granule-containing cells. Children are immunocompromised because of impaired phagocytosis and natural killer cell function. The genetic defect is a mutation of the LYST (lysosomal trafficking regulator) gene on chromosome 1. During an accelerated phase, lymphocytes and histiocytes can accumulate in the liver, spleen, lymph nodes, and bone marrow. High doses of methylprednisolone and splenectomy may be helpful during this phase, but allogeneic bone marrow transplantation is performed whenever possible.

▸ Griscelli syndrome. A mutation on the RAB27A gene of chromosome 15 causes this severe, autosomal recessive immunodeficiency syndrome. Many children develop hemophagocytic syndrome early, with frequent infectious episodes. Children may develop pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Delayed-type cutaneous hypersensitivity and impaired natural killer function contribute to immunodeficiency. Allogeneic bone marrow transplantation is the treatment of choice.

▸ Elejalde syndrome. This autosomal recessive disease is caused by a mutation in the gene MYO5A on chromosome 15. Severe neurologic abnormalities are seen, including hypotonia, mental retardation, and relentlessly progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomes are associated with the syndrome.

▸ Silvery hair syndrome without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin on chromosome 2 have silvery hair and bronzed skin following sun exposure; however they do not exhibit immunologic or neurologic complications.

LAS VEGAS — Genetic disorders associated with silvery hair are almost uniformly fatal in children, most often as a result of accompanying immunologic or neurologic abnormalities, according to Dr. Carola Durán-McKinster.

Natural light reveals hair the color of lead that has a "peculiar" shine in children with Chédiak-Higashi syndrome, Griscelli syndrome, and Elejalde syndrome, and in the rare child whose unusual pigmentation is not associated with systemic defects, said Dr. Durán-McKinster at a dermatology seminar sponsored by Skin Disease Education Foundation.

A natural history study of children with these syndromes at the National Institute of Pediatrics of Mexico, where Dr. Durán-McKinster is head of pediatric dermatology, determined that the diseases were fatal in 8 of 10 children with Chédiak-Higashi syndrome, all 7 children with Griscelli syndrome, and 8 of 10 children with traditional Elejalde syndrome.

Four children with silvery hair who did not fit diagnostic criteria for any systemic syndrome all survived, she said.

Children with silvery hair syndromes have skin that is so hypopigmented at birth that they may resemble children with albinism.

However, after exposure to sunlight, their skin becomes deeply, persistently bronzed, explained Dr. Durán-McKinster, who serves on the dermatology faculty at Universidad Nacional Autónoma de México.

A careful examination of the hair of infants can be critical to making a diagnosis, often with important prognostic and treatment implications, she stressed.

"Hair can be a very, very good tool to making the diagnosis of genodermatoses," she said. "Pigment in the hair shaft is very special."

A decrease or total loss of color in the hair or skin can arise from a mutation in any of 127 genes involved in the complex pigmentation process, which involves distribution of melanin polymers produced in the melanocytes and transferred to neighboring keratinocytes.

Mutations in genes that express two critical proteins involved in this process, myosin 5A and Rab27, are key to abnormalities in two key silvery hair syndromes, Elejalde syndrome and Griscelli syndrome, respectively, said Dr. Durán-McKinster.

Dermatologists may readily recognize the very light hair characteristic of albinism or poliosis (often, a white forelock) that may be an isolated genetic feature or may be associated with deafness, as in Waardenburg's syndrome.

Unusual silvery-gray hair is much less common, and should be investigated with light microscopy and a biopsy.

Histopathologic findings include a clustering of melanin in basal melanocytes, with nearly absent pigment in adjacent keratinocytes—features especially well visualized with Fontana-Masson stain, said Dr. Durán-McKinster.

Light microscopy of the hair shaft can distinguish a pattern of melanin distribution virtually pathognomonic for Chédiak-Higashi syndrome. The "very, very small clumps" of melanin are evenly distributed, in contrast to giant and small clumps of melanin distributed in an irregular pattern in Elejalde syndrome.

Clinically, the hair of a child with Elejalde syndrome may shine more brightly, since there is more space between melanin clumps to reflect light, she explained.

A prompt and accurate diagnosis of the underlying syndrome can lead to appropriate immunologic or neurologic testing and management, which may include antibiotics and antivirals, intravenous immunoglobulin, blood transfusions, and bone marrow transplantation.

Dr. Durán-McKinster disclosed having no relevant conflicts of interest.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

The Genetics of Silvery Hair

Dr. Durán-McKinster described the following syndromes:

▸ Chédiak-Higasi syndrome. In this rare, autosomal recessive disorder, giant inclusion bodies can be found in all granule-containing cells. Children are immunocompromised because of impaired phagocytosis and natural killer cell function. The genetic defect is a mutation of the LYST (lysosomal trafficking regulator) gene on chromosome 1. During an accelerated phase, lymphocytes and histiocytes can accumulate in the liver, spleen, lymph nodes, and bone marrow. High doses of methylprednisolone and splenectomy may be helpful during this phase, but allogeneic bone marrow transplantation is performed whenever possible.

▸ Griscelli syndrome. A mutation on the RAB27A gene of chromosome 15 causes this severe, autosomal recessive immunodeficiency syndrome. Many children develop hemophagocytic syndrome early, with frequent infectious episodes. Children may develop pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and hypoproteinemia. Delayed-type cutaneous hypersensitivity and impaired natural killer function contribute to immunodeficiency. Allogeneic bone marrow transplantation is the treatment of choice.

▸ Elejalde syndrome. This autosomal recessive disease is caused by a mutation in the gene MYO5A on chromosome 15. Severe neurologic abnormalities are seen, including hypotonia, mental retardation, and relentlessly progressive psychomotor impairment until death. Ocular abnormalities and abnormal melanocytes and melanosomes are associated with the syndrome.

▸ Silvery hair syndrome without associated abnormalities. Children with a syndrome resulting from a mutation of the gene that encodes for melanophilin on chromosome 2 have silvery hair and bronzed skin following sun exposure; however they do not exhibit immunologic or neurologic complications.

LAS VEGAS — Too often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, Dr. Fred Ghali relishes the chance to tell a family: "No worries."

Such is the case with three common but sometimes unrecognized diagnoses presenting to Dr. Ghali's pediatric dermatology practice in Grapevine, Tex.

He shared these benign conditions with his colleagues at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Psuedo acne. Most parents recognize that children are maturing earlier these days, but they still tend to panic when they see what they think is acne developing in their 5- or 6-year-old. Take a good, hard look at the location and pattern of the small white papules on a young child's nose, suggests Dr. Ghali.

The papules are likely "pseudo acne," small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature cysts rupture, they may take on an inflammatory appearance that resembles acne.

Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary. However, Dr. Ghali's treatment of choice is pretty simple: "Reassurance to the family."

▸ Striking striae. Mom may gasp when she sees deep, dark, horizontal marks lining the back of her 13- or 14-year-old son.

"It is quite impressive when you see this," Dr. Ghali acknowledged, pointing to the welt-like striations.

He first theorized that the bands of discoloration might be caused by the carrying of heavy backpacks, or might be the result of wacky skateboard maneuvers.

"The bottom line is [adolescents with this condition] have lots of vertical growth over a short period of time. They're usually [white] children who are extremely skinny," he said.

The striae will tend to fade over time, resolving far better than striae of pregnancy. No treatment is necessary.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans. But what about when you see these symptoms in a child of normal weight, with no other signs of metabolic illness?

"You can look like a hero," said Dr. Ghali. "Just walk in with a little bit of alcohol and wipe it off."

Known by many names ("kitschy keratosis" when he was in training), this condition, common to young children, requires just two words to concerned parents: "No worries," said Dr. Ghali.

SDEF and SKIN & ALLERGY NEWS are subsidiaries of Elsevier.

LAS VEGAS — Too often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, Dr. Fred Ghali relishes the chance to tell a family: "No worries."

Such is the case with three common but sometimes unrecognized diagnoses presenting to Dr. Ghali's pediatric dermatology practice in Grapevine, Tex.

He shared these benign conditions with his colleagues at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Psuedo acne. Most parents recognize that children are maturing earlier these days, but they still tend to panic when they see what they think is acne developing in their 5- or 6-year-old. Take a good, hard look at the location and pattern of the small white papules on a young child's nose, suggests Dr. Ghali.

The papules are likely "pseudo acne," small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature cysts rupture, they may take on an inflammatory appearance that resembles acne.

Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary. However, Dr. Ghali's treatment of choice is pretty simple: "Reassurance to the family."

▸ Striking striae. Mom may gasp when she sees deep, dark, horizontal marks lining the back of her 13- or 14-year-old son.

"It is quite impressive when you see this," Dr. Ghali acknowledged, pointing to the welt-like striations.

He first theorized that the bands of discoloration might be caused by the carrying of heavy backpacks, or might be the result of wacky skateboard maneuvers.

"The bottom line is [adolescents with this condition] have lots of vertical growth over a short period of time. They're usually [white] children who are extremely skinny," he said.

The striae will tend to fade over time, resolving far better than striae of pregnancy. No treatment is necessary.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans. But what about when you see these symptoms in a child of normal weight, with no other signs of metabolic illness?

"You can look like a hero," said Dr. Ghali. "Just walk in with a little bit of alcohol and wipe it off."

Known by many names ("kitschy keratosis" when he was in training), this condition, common to young children, requires just two words to concerned parents: "No worries," said Dr. Ghali.

SDEF and SKIN & ALLERGY NEWS are subsidiaries of Elsevier.

LAS VEGAS — Too often faced with worrisome hemangiomas, grim genetic dermatoses, or serious drug eruptions, Dr. Fred Ghali relishes the chance to tell a family: "No worries."

Such is the case with three common but sometimes unrecognized diagnoses presenting to Dr. Ghali's pediatric dermatology practice in Grapevine, Tex.

He shared these benign conditions with his colleagues at a dermatology seminar sponsored by Skin Disease Education Foundation:

▸ Psuedo acne. Most parents recognize that children are maturing earlier these days, but they still tend to panic when they see what they think is acne developing in their 5- or 6-year-old. Take a good, hard look at the location and pattern of the small white papules on a young child's nose, suggests Dr. Ghali.

The papules are likely "pseudo acne," small milia created when a child constantly rubs his or her nose, often in response to nasal allergies. If these miniature cysts rupture, they may take on an inflammatory appearance that resembles acne.

Less nose-rubbing will help, and topical comedolytics and antibiotics may be prescribed if necessary. However, Dr. Ghali's treatment of choice is pretty simple: "Reassurance to the family."

▸ Striking striae. Mom may gasp when she sees deep, dark, horizontal marks lining the back of her 13- or 14-year-old son.

"It is quite impressive when you see this," Dr. Ghali acknowledged, pointing to the welt-like striations.

He first theorized that the bands of discoloration might be caused by the carrying of heavy backpacks, or might be the result of wacky skateboard maneuvers.

"The bottom line is [adolescents with this condition] have lots of vertical growth over a short period of time. They're usually [white] children who are extremely skinny," he said.

The striae will tend to fade over time, resolving far better than striae of pregnancy. No treatment is necessary.

▸ Retention keratosis. Darkly pigmented, nonpruritic regions in the flexural areas of a child's neck or underarm might point to a diagnosis of acanthosis nigricans. But what about when you see these symptoms in a child of normal weight, with no other signs of metabolic illness?

"You can look like a hero," said Dr. Ghali. "Just walk in with a little bit of alcohol and wipe it off."

Known by many names ("kitschy keratosis" when he was in training), this condition, common to young children, requires just two words to concerned parents: "No worries," said Dr. Ghali.

SDEF and SKIN & ALLERGY NEWS are subsidiaries of Elsevier.

LAS VEGAS — Most experts in psychodermatology long ago abandoned the psychoanalytic theory of atopic eczema, characterized in 1940 by Dr. Franz Alexander as an outgrowth of a child's emotional angst at being unable to express anger and hostility arising from maternal rejection.

Still, increasing evidence points to a psychoneuroimmunologic "setup" for atopic dermatitis (AD), if not an eczema personality profile, asserts Dr. Torello M. Lotti, professor and chair of dermatology at the University of Florence, Italy.

Dr. Lotti and other researchers have hypothesized that an interconnection between genetic and environmental factors may predispose a patient to allergic inflammation, which may then cascade in a vulnerable individual into a long-lasting diminished capacity for appropriate protective reactivity within the hypothalamus-pituitary-adrenal (HPA) axis.

Certain responses to experimental conditions point to notable differences in the psycho-neuroendocrine-immune function of people with atopic dermatitis and other inflammatory allergic diseases, Dr. Lotti said during a seminar on dermatology sponsored by Skin Disease Education Foundation.

He cited numerous studies:

▸ Diurnal plasma cortisol (stress marker) variations in AD patients were found to rise and fall with atopy-relevant inflammatory parameters, with associated waxing and waning of allergic symptom severity (J. Clin. Invest. 1992;90:596–603).

▸ AD-like symptoms were actually precipitated in healthy volunteers after treatment with the glucocorticoid receptor antagonist RU 486 (J. Clin. Endocrinol. Metab 1990;71:1474–80).

▸ When exposed to experimental stressor conditions (asking volunteers to speak and do mental arithmetic tasks in front of an audience), eosinophil counts and IgE levels rose significantly in atopic eczema sufferers, but not in healthy volunteers (J. Neuroimmunol. 2002;129:161–7).

▸ Finally, epidemiologic evidence appears to bolster the argument that stress—either exerted by outside events or exquisitely experienced by a vulnerable personality—contributes to the cycle of events perpetuating atopic dermatitis, he said.

A severe shock or emotional event has been found to precede the onset or aggravation of AD in patients in early dermatologic studies, which also tracks with his clinical experience, he noted. An increasing prevalence of AD in children in the Western World may be symptomatic of the more highly-stressed, pressured environments in which they live.

In Dr. Lotti's view, a "biochemical setup" for atopic dermatitis activates not only stress (influencing the sympathetic nervous system and immune response), but also behavior and personality.

An appropriate approach, he said, is to utilize treatments that impact psychological symptoms of distress as well as physiologic symptoms such as pruritus.

He favors doxepin (10 mg at bedtime) or amitriptyline (starting at a dose of 50 mg/day) over antihistamines for "the itch of atopic dermatitis," which he said "is not a regular itch."

Direct acknowledgement of the psychological contributors to atopic dermatitis facilitates "liaison consultations," in which Dr. Lotti sees patients sometimes in the same room at the same time as do psychologists or psychiatrists.

Dr. Lotti disclosed receiving grant or research support or speakers bureau contributions from Merck-Serono, Wyeth, Abbott, and Schering-Plough.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

LAS VEGAS — Most experts in psychodermatology long ago abandoned the psychoanalytic theory of atopic eczema, characterized in 1940 by Dr. Franz Alexander as an outgrowth of a child's emotional angst at being unable to express anger and hostility arising from maternal rejection.

Still, increasing evidence points to a psychoneuroimmunologic "setup" for atopic dermatitis (AD), if not an eczema personality profile, asserts Dr. Torello M. Lotti, professor and chair of dermatology at the University of Florence, Italy.

Dr. Lotti and other researchers have hypothesized that an interconnection between genetic and environmental factors may predispose a patient to allergic inflammation, which may then cascade in a vulnerable individual into a long-lasting diminished capacity for appropriate protective reactivity within the hypothalamus-pituitary-adrenal (HPA) axis.

Certain responses to experimental conditions point to notable differences in the psycho-neuroendocrine-immune function of people with atopic dermatitis and other inflammatory allergic diseases, Dr. Lotti said during a seminar on dermatology sponsored by Skin Disease Education Foundation.

He cited numerous studies:

▸ Diurnal plasma cortisol (stress marker) variations in AD patients were found to rise and fall with atopy-relevant inflammatory parameters, with associated waxing and waning of allergic symptom severity (J. Clin. Invest. 1992;90:596–603).

▸ AD-like symptoms were actually precipitated in healthy volunteers after treatment with the glucocorticoid receptor antagonist RU 486 (J. Clin. Endocrinol. Metab 1990;71:1474–80).

▸ When exposed to experimental stressor conditions (asking volunteers to speak and do mental arithmetic tasks in front of an audience), eosinophil counts and IgE levels rose significantly in atopic eczema sufferers, but not in healthy volunteers (J. Neuroimmunol. 2002;129:161–7).

▸ Finally, epidemiologic evidence appears to bolster the argument that stress—either exerted by outside events or exquisitely experienced by a vulnerable personality—contributes to the cycle of events perpetuating atopic dermatitis, he said.

A severe shock or emotional event has been found to precede the onset or aggravation of AD in patients in early dermatologic studies, which also tracks with his clinical experience, he noted. An increasing prevalence of AD in children in the Western World may be symptomatic of the more highly-stressed, pressured environments in which they live.

In Dr. Lotti's view, a "biochemical setup" for atopic dermatitis activates not only stress (influencing the sympathetic nervous system and immune response), but also behavior and personality.

An appropriate approach, he said, is to utilize treatments that impact psychological symptoms of distress as well as physiologic symptoms such as pruritus.

He favors doxepin (10 mg at bedtime) or amitriptyline (starting at a dose of 50 mg/day) over antihistamines for "the itch of atopic dermatitis," which he said "is not a regular itch."

Direct acknowledgement of the psychological contributors to atopic dermatitis facilitates "liaison consultations," in which Dr. Lotti sees patients sometimes in the same room at the same time as do psychologists or psychiatrists.

Dr. Lotti disclosed receiving grant or research support or speakers bureau contributions from Merck-Serono, Wyeth, Abbott, and Schering-Plough.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.

LAS VEGAS — Most experts in psychodermatology long ago abandoned the psychoanalytic theory of atopic eczema, characterized in 1940 by Dr. Franz Alexander as an outgrowth of a child's emotional angst at being unable to express anger and hostility arising from maternal rejection.

Still, increasing evidence points to a psychoneuroimmunologic "setup" for atopic dermatitis (AD), if not an eczema personality profile, asserts Dr. Torello M. Lotti, professor and chair of dermatology at the University of Florence, Italy.

Dr. Lotti and other researchers have hypothesized that an interconnection between genetic and environmental factors may predispose a patient to allergic inflammation, which may then cascade in a vulnerable individual into a long-lasting diminished capacity for appropriate protective reactivity within the hypothalamus-pituitary-adrenal (HPA) axis.

Certain responses to experimental conditions point to notable differences in the psycho-neuroendocrine-immune function of people with atopic dermatitis and other inflammatory allergic diseases, Dr. Lotti said during a seminar on dermatology sponsored by Skin Disease Education Foundation.

He cited numerous studies:

▸ Diurnal plasma cortisol (stress marker) variations in AD patients were found to rise and fall with atopy-relevant inflammatory parameters, with associated waxing and waning of allergic symptom severity (J. Clin. Invest. 1992;90:596–603).

▸ AD-like symptoms were actually precipitated in healthy volunteers after treatment with the glucocorticoid receptor antagonist RU 486 (J. Clin. Endocrinol. Metab 1990;71:1474–80).

▸ When exposed to experimental stressor conditions (asking volunteers to speak and do mental arithmetic tasks in front of an audience), eosinophil counts and IgE levels rose significantly in atopic eczema sufferers, but not in healthy volunteers (J. Neuroimmunol. 2002;129:161–7).

▸ Finally, epidemiologic evidence appears to bolster the argument that stress—either exerted by outside events or exquisitely experienced by a vulnerable personality—contributes to the cycle of events perpetuating atopic dermatitis, he said.

A severe shock or emotional event has been found to precede the onset or aggravation of AD in patients in early dermatologic studies, which also tracks with his clinical experience, he noted. An increasing prevalence of AD in children in the Western World may be symptomatic of the more highly-stressed, pressured environments in which they live.

In Dr. Lotti's view, a "biochemical setup" for atopic dermatitis activates not only stress (influencing the sympathetic nervous system and immune response), but also behavior and personality.

An appropriate approach, he said, is to utilize treatments that impact psychological symptoms of distress as well as physiologic symptoms such as pruritus.

He favors doxepin (10 mg at bedtime) or amitriptyline (starting at a dose of 50 mg/day) over antihistamines for "the itch of atopic dermatitis," which he said "is not a regular itch."

Direct acknowledgement of the psychological contributors to atopic dermatitis facilitates "liaison consultations," in which Dr. Lotti sees patients sometimes in the same room at the same time as do psychologists or psychiatrists.

Dr. Lotti disclosed receiving grant or research support or speakers bureau contributions from Merck-Serono, Wyeth, Abbott, and Schering-Plough.

SDEF and SKIN & ALLERGY NEWS are wholly owned subsidiaries of Elsevier.