Diana Mahoney

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for U.S. adults aged 25–75 years and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey (1971–1975) to 10.5% by the third survey (1988–1994), but then decreased to 7.5% in the fourth survey (1999–2004).

The low-risk-factor profile included these variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; BP less than 120/80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. Now, “fewer than 10% of Americans are meeting the low-risk goals.”

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%). For blood pressure, the low-risk percentage was higher for the period 1988–1994 than for the 1971–1975 period, but it decreased for the period 1999–2004.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health in Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, wrote that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia.”

The findings “provide an important signal that the health of Americans is at a crossroad. The current path leads toward increasing adiposity, diabetes mellitus, cardiovascular disease, and disability and an unfit, socially isolated population stuffed with pills and subjected to frequent palliative procedures.”

To change course, they stressed, physicians can help by working with their patients one on one but “their help is needed even more as leaders in the effort to reshape policies and our environment.” (Circulation 2009;120:1171–3).

The authors report having no financial disclosures related to this report.

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for U.S. adults aged 25–75 years and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey (1971–1975) to 10.5% by the third survey (1988–1994), but then decreased to 7.5% in the fourth survey (1999–2004).

The low-risk-factor profile included these variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; BP less than 120/80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. Now, “fewer than 10% of Americans are meeting the low-risk goals.”

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%). For blood pressure, the low-risk percentage was higher for the period 1988–1994 than for the 1971–1975 period, but it decreased for the period 1999–2004.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health in Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, wrote that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia.”

The findings “provide an important signal that the health of Americans is at a crossroad. The current path leads toward increasing adiposity, diabetes mellitus, cardiovascular disease, and disability and an unfit, socially isolated population stuffed with pills and subjected to frequent palliative procedures.”

To change course, they stressed, physicians can help by working with their patients one on one but “their help is needed even more as leaders in the effort to reshape policies and our environment.” (Circulation 2009;120:1171–3).

The authors report having no financial disclosures related to this report.

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for U.S. adults aged 25–75 years and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey (1971–1975) to 10.5% by the third survey (1988–1994), but then decreased to 7.5% in the fourth survey (1999–2004).

The low-risk-factor profile included these variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; BP less than 120/80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. Now, “fewer than 10% of Americans are meeting the low-risk goals.”

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%). For blood pressure, the low-risk percentage was higher for the period 1988–1994 than for the 1971–1975 period, but it decreased for the period 1999–2004.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health in Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, wrote that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia.”

The findings “provide an important signal that the health of Americans is at a crossroad. The current path leads toward increasing adiposity, diabetes mellitus, cardiovascular disease, and disability and an unfit, socially isolated population stuffed with pills and subjected to frequent palliative procedures.”

To change course, they stressed, physicians can help by working with their patients one on one but “their help is needed even more as leaders in the effort to reshape policies and our environment.” (Circulation 2009;120:1171–3).

The authors report having no financial disclosures related to this report.

New provisional criteria for the diagnosis of very early systemic sclerosis aim to close the “unacceptably wide” gap between the onset of early signs of the autoimmune connective-tissue disease and the time of disease diagnosis, according to Dr. Marco Matucci-Cerinic.

The current diagnostic standard is based on the signs and symptoms of overt disease “and does not adequately address the earliest disease predictors,” said Dr. Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy). In addition to helping rheumatologists in practice, the proposed criteria could also be valuable to the EULAR/ACR systemic sclerosis reclassification project, they stated (Ann. Rheum. Dis. 2009;68:1377–80).

“Systemic sclerosis has the highest case-specific mortality of any of the connective tissue diseases, which is likely due to the fact that the disease is often well established by the time it is diagnosed,” Dr. Matucci-Cerinic said at the annual European Congress of Rheumatology in Copenhagen in June.

In an effort to bridge the gap, Dr. Matucci-Cerinic and colleagues in the VEDOSS (Very Early Diagnosis of Systemic Sclerosis) project of the EULAR Scleroderma Trials and Research (EUSTAR) group have developed evidence-based criteria for the diagnosis of very early disease.

The proposed definition requires three major criteria (including Raynaud's phenomenon, disease-specific antibodies, and pathognomonic microvascular alterations detected by nail fold videocapillaroscopy), or two major criteria and one additional criterion (including calcinosis, puffy fingers, digital ulcers, dysfunction of the esophageal sphincter, telangiectasia, and ground glass appearance on high-resolution chest CT), Dr. Matucci-Cerinic said.

Based on the criteria, patients with Raynaud's phenomena and hand edema (“puffy fingers”), which commonly present together in early disease, should be referred for capillaroscopy as well as serology to detect antinuclear, anticentromere, antitopoisomerase I, and extractable nuclear antigen antibodies.

An important component of the VEDOSS project is the European Union–wide call for primary care clinicians to refer all patients who exhibit two or more of the early symptoms to a rheumatologist or scleroderma center, he said.

To date, several drugs—including ACE inhibitors, calcium channel blockers, cyclophosphamide, methotrexate, and endothelin receptor antagonists—have improved the outcomes of patients with established disease, according to EULAR/EUSTAR systemic sclerosis treatment recommendations issued earlier this year (Ann. Rheum. Dis. 2009;68:620–8). The possibility that earlier, more aggressive treatment with these or other agents that are being evaluated in clinical trials might alter the progression of disease and potentially prevent irreversible organ damage warrants investigation, said Dr. Alan Tyndall of the University of Basel (Switzerland).

New provisional criteria for the diagnosis of very early systemic sclerosis aim to close the “unacceptably wide” gap between the onset of early signs of the autoimmune connective-tissue disease and the time of disease diagnosis, according to Dr. Marco Matucci-Cerinic.

The current diagnostic standard is based on the signs and symptoms of overt disease “and does not adequately address the earliest disease predictors,” said Dr. Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy). In addition to helping rheumatologists in practice, the proposed criteria could also be valuable to the EULAR/ACR systemic sclerosis reclassification project, they stated (Ann. Rheum. Dis. 2009;68:1377–80).

“Systemic sclerosis has the highest case-specific mortality of any of the connective tissue diseases, which is likely due to the fact that the disease is often well established by the time it is diagnosed,” Dr. Matucci-Cerinic said at the annual European Congress of Rheumatology in Copenhagen in June.

In an effort to bridge the gap, Dr. Matucci-Cerinic and colleagues in the VEDOSS (Very Early Diagnosis of Systemic Sclerosis) project of the EULAR Scleroderma Trials and Research (EUSTAR) group have developed evidence-based criteria for the diagnosis of very early disease.

The proposed definition requires three major criteria (including Raynaud's phenomenon, disease-specific antibodies, and pathognomonic microvascular alterations detected by nail fold videocapillaroscopy), or two major criteria and one additional criterion (including calcinosis, puffy fingers, digital ulcers, dysfunction of the esophageal sphincter, telangiectasia, and ground glass appearance on high-resolution chest CT), Dr. Matucci-Cerinic said.

Based on the criteria, patients with Raynaud's phenomena and hand edema (“puffy fingers”), which commonly present together in early disease, should be referred for capillaroscopy as well as serology to detect antinuclear, anticentromere, antitopoisomerase I, and extractable nuclear antigen antibodies.

An important component of the VEDOSS project is the European Union–wide call for primary care clinicians to refer all patients who exhibit two or more of the early symptoms to a rheumatologist or scleroderma center, he said.

To date, several drugs—including ACE inhibitors, calcium channel blockers, cyclophosphamide, methotrexate, and endothelin receptor antagonists—have improved the outcomes of patients with established disease, according to EULAR/EUSTAR systemic sclerosis treatment recommendations issued earlier this year (Ann. Rheum. Dis. 2009;68:620–8). The possibility that earlier, more aggressive treatment with these or other agents that are being evaluated in clinical trials might alter the progression of disease and potentially prevent irreversible organ damage warrants investigation, said Dr. Alan Tyndall of the University of Basel (Switzerland).

New provisional criteria for the diagnosis of very early systemic sclerosis aim to close the “unacceptably wide” gap between the onset of early signs of the autoimmune connective-tissue disease and the time of disease diagnosis, according to Dr. Marco Matucci-Cerinic.

The current diagnostic standard is based on the signs and symptoms of overt disease “and does not adequately address the earliest disease predictors,” said Dr. Matucci-Cerinic, professor of rheumatology and medicine at the University of Florence (Italy). In addition to helping rheumatologists in practice, the proposed criteria could also be valuable to the EULAR/ACR systemic sclerosis reclassification project, they stated (Ann. Rheum. Dis. 2009;68:1377–80).

“Systemic sclerosis has the highest case-specific mortality of any of the connective tissue diseases, which is likely due to the fact that the disease is often well established by the time it is diagnosed,” Dr. Matucci-Cerinic said at the annual European Congress of Rheumatology in Copenhagen in June.

In an effort to bridge the gap, Dr. Matucci-Cerinic and colleagues in the VEDOSS (Very Early Diagnosis of Systemic Sclerosis) project of the EULAR Scleroderma Trials and Research (EUSTAR) group have developed evidence-based criteria for the diagnosis of very early disease.

The proposed definition requires three major criteria (including Raynaud's phenomenon, disease-specific antibodies, and pathognomonic microvascular alterations detected by nail fold videocapillaroscopy), or two major criteria and one additional criterion (including calcinosis, puffy fingers, digital ulcers, dysfunction of the esophageal sphincter, telangiectasia, and ground glass appearance on high-resolution chest CT), Dr. Matucci-Cerinic said.

Based on the criteria, patients with Raynaud's phenomena and hand edema (“puffy fingers”), which commonly present together in early disease, should be referred for capillaroscopy as well as serology to detect antinuclear, anticentromere, antitopoisomerase I, and extractable nuclear antigen antibodies.

An important component of the VEDOSS project is the European Union–wide call for primary care clinicians to refer all patients who exhibit two or more of the early symptoms to a rheumatologist or scleroderma center, he said.

To date, several drugs—including ACE inhibitors, calcium channel blockers, cyclophosphamide, methotrexate, and endothelin receptor antagonists—have improved the outcomes of patients with established disease, according to EULAR/EUSTAR systemic sclerosis treatment recommendations issued earlier this year (Ann. Rheum. Dis. 2009;68:620–8). The possibility that earlier, more aggressive treatment with these or other agents that are being evaluated in clinical trials might alter the progression of disease and potentially prevent irreversible organ damage warrants investigation, said Dr. Alan Tyndall of the University of Basel (Switzerland).

Keep an open mind when considering skin signs and symptoms in children because dermatologic conditions may be a manifestation of systemic disease, according to Dr. Lawrence Eichenfield.

Recognizing the chronic nature of some of these conditions, and employing a collaborative approach when necessary, can substantially streamline management, Dr. Eichenfield reported.

Henoch-Schönlein

Dr. Eichenfield described Henoch-Schönlein purpura, a type of vasculitis that occurs most frequently in children and young adults and is characterized by abdominal cramps, hematuria, and a purpuric rash mainly on the lower legs and buttocks.

In addition to the skin and the gastrointestinal tract, the joints and kidneys are also end-organ targets, noted Dr. Eichenfield, professor of pediatrics and dermatology at the University of California, San Diego, at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Arthralgia or arthritis—most commonly in the knees and ankles but also in the wrists, elbows, fingers, and toes—is reported in 65%–85% of the cases, and sometimes precedes the rash. Renal involvement has been estimated to occur in 10%–60% of cases, typically within the first month (and often within the first week) of the appearance of the rash, according to Dr. Eichenfield.

Because of the risk of nephritis, urinalysis is a key consideration in the management of Henoch-Schönlein purpura. A negative urinalysis during week 1 should be followed by repeat tests for up to 6 months, based on the literature, he added.

The clinical course averages about 4 weeks. Treatment can include NSAIDs for the joint symptoms and corticosteroids, although the use of the latter for this indication remains controversial, he noted, referring to data in the literature demonstrating the efficacy of prednisone for reducing abdominal and joint pain and for the treatment, but not prevention, of renal involvement.

Juvenile Dermatomyositis

The cutaneous findings of juvenile dermatomyositis, which affects 3,000–5,000 children in the United States, include Gottron's papules; heliotrope rash; periungual telangiectasias; photosensitivity or scaly erythema of the face, neck, anterior chest, or shawl area; calcinosis cutis; pruritic eruption on exposed surfaces; and scaly scalp or diffuse hair loss.

These symptoms provide a window into autoimmune vasculopathy, Dr. Eichenfield said.

The disease is typically associated with progressive symmetric involvement of the proximal musculature. Gowers' sign, difficulty climbing stairs, arising from chairs, and combing hair—as well as muscle enzyme elevations, arrhythmia, dyspnea, dysphonia, and dysphagia—may be observed and should be assessed in the review of systems.

Neonatal Lupus Erythematosus

Dr. Eichenfield also described neonatal lupus erythematosus, which typically presents within the first 12 weeks of an infant's life with scaling and facial eruptions that may be mistaken for tinea.

Because of the associated cardiac, hepatic, hematologic, and central nervous system considerations, a full work-up for accurate diagnosis is essential.

The work-up should include a head circumference measure; serological testing for renal function, cytopenia, liver enzyme elevations, antinuclear antibody, anti-dsDNA, anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B; electrocardiography; and, potentially, a skin biopsy, he noted. Examples of other systemic conditions that may present with skin signs in children and young adults include minocycline-induced autoimmunity, psoriasis, and pediatric morphea, according to Dr. Eichenfield.

He reported that he did not have any conflicts of interest in regards to his presentation. SDEF and this news organization are owned by Elsevier.

This CT image shows extensive soft-tissue calcifications in dermatomyo-sitis, largely in the subcutan-eous gluteal fat (arrowheads) in this 19-year-old female with severe multisystemic involvement.

Source ©Elsevier

Arthritis or arthralgia occurs in up to 85% of Henoch-Schönlein cases, renal damage in up to 60%.

Source Dr. Eichenfield

Barium enema postevacuation film shows marginal filling defects in the distal ileum in Henoch-Schönlein.

Source ©Elsevier

Keep an open mind when considering skin signs and symptoms in children because dermatologic conditions may be a manifestation of systemic disease, according to Dr. Lawrence Eichenfield.

Recognizing the chronic nature of some of these conditions, and employing a collaborative approach when necessary, can substantially streamline management, Dr. Eichenfield reported.

Henoch-Schönlein

Dr. Eichenfield described Henoch-Schönlein purpura, a type of vasculitis that occurs most frequently in children and young adults and is characterized by abdominal cramps, hematuria, and a purpuric rash mainly on the lower legs and buttocks.

In addition to the skin and the gastrointestinal tract, the joints and kidneys are also end-organ targets, noted Dr. Eichenfield, professor of pediatrics and dermatology at the University of California, San Diego, at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Arthralgia or arthritis—most commonly in the knees and ankles but also in the wrists, elbows, fingers, and toes—is reported in 65%–85% of the cases, and sometimes precedes the rash. Renal involvement has been estimated to occur in 10%–60% of cases, typically within the first month (and often within the first week) of the appearance of the rash, according to Dr. Eichenfield.

Because of the risk of nephritis, urinalysis is a key consideration in the management of Henoch-Schönlein purpura. A negative urinalysis during week 1 should be followed by repeat tests for up to 6 months, based on the literature, he added.

The clinical course averages about 4 weeks. Treatment can include NSAIDs for the joint symptoms and corticosteroids, although the use of the latter for this indication remains controversial, he noted, referring to data in the literature demonstrating the efficacy of prednisone for reducing abdominal and joint pain and for the treatment, but not prevention, of renal involvement.

Juvenile Dermatomyositis

The cutaneous findings of juvenile dermatomyositis, which affects 3,000–5,000 children in the United States, include Gottron's papules; heliotrope rash; periungual telangiectasias; photosensitivity or scaly erythema of the face, neck, anterior chest, or shawl area; calcinosis cutis; pruritic eruption on exposed surfaces; and scaly scalp or diffuse hair loss.

These symptoms provide a window into autoimmune vasculopathy, Dr. Eichenfield said.

The disease is typically associated with progressive symmetric involvement of the proximal musculature. Gowers' sign, difficulty climbing stairs, arising from chairs, and combing hair—as well as muscle enzyme elevations, arrhythmia, dyspnea, dysphonia, and dysphagia—may be observed and should be assessed in the review of systems.

Neonatal Lupus Erythematosus

Dr. Eichenfield also described neonatal lupus erythematosus, which typically presents within the first 12 weeks of an infant's life with scaling and facial eruptions that may be mistaken for tinea.

Because of the associated cardiac, hepatic, hematologic, and central nervous system considerations, a full work-up for accurate diagnosis is essential.

The work-up should include a head circumference measure; serological testing for renal function, cytopenia, liver enzyme elevations, antinuclear antibody, anti-dsDNA, anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B; electrocardiography; and, potentially, a skin biopsy, he noted. Examples of other systemic conditions that may present with skin signs in children and young adults include minocycline-induced autoimmunity, psoriasis, and pediatric morphea, according to Dr. Eichenfield.

He reported that he did not have any conflicts of interest in regards to his presentation. SDEF and this news organization are owned by Elsevier.

This CT image shows extensive soft-tissue calcifications in dermatomyo-sitis, largely in the subcutan-eous gluteal fat (arrowheads) in this 19-year-old female with severe multisystemic involvement.

Source ©Elsevier

Arthritis or arthralgia occurs in up to 85% of Henoch-Schönlein cases, renal damage in up to 60%.

Source Dr. Eichenfield

Barium enema postevacuation film shows marginal filling defects in the distal ileum in Henoch-Schönlein.

Source ©Elsevier

Keep an open mind when considering skin signs and symptoms in children because dermatologic conditions may be a manifestation of systemic disease, according to Dr. Lawrence Eichenfield.

Recognizing the chronic nature of some of these conditions, and employing a collaborative approach when necessary, can substantially streamline management, Dr. Eichenfield reported.

Henoch-Schönlein

Dr. Eichenfield described Henoch-Schönlein purpura, a type of vasculitis that occurs most frequently in children and young adults and is characterized by abdominal cramps, hematuria, and a purpuric rash mainly on the lower legs and buttocks.

In addition to the skin and the gastrointestinal tract, the joints and kidneys are also end-organ targets, noted Dr. Eichenfield, professor of pediatrics and dermatology at the University of California, San Diego, at the women's and pediatric dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).

Arthralgia or arthritis—most commonly in the knees and ankles but also in the wrists, elbows, fingers, and toes—is reported in 65%–85% of the cases, and sometimes precedes the rash. Renal involvement has been estimated to occur in 10%–60% of cases, typically within the first month (and often within the first week) of the appearance of the rash, according to Dr. Eichenfield.

Because of the risk of nephritis, urinalysis is a key consideration in the management of Henoch-Schönlein purpura. A negative urinalysis during week 1 should be followed by repeat tests for up to 6 months, based on the literature, he added.

The clinical course averages about 4 weeks. Treatment can include NSAIDs for the joint symptoms and corticosteroids, although the use of the latter for this indication remains controversial, he noted, referring to data in the literature demonstrating the efficacy of prednisone for reducing abdominal and joint pain and for the treatment, but not prevention, of renal involvement.

Juvenile Dermatomyositis

The cutaneous findings of juvenile dermatomyositis, which affects 3,000–5,000 children in the United States, include Gottron's papules; heliotrope rash; periungual telangiectasias; photosensitivity or scaly erythema of the face, neck, anterior chest, or shawl area; calcinosis cutis; pruritic eruption on exposed surfaces; and scaly scalp or diffuse hair loss.

These symptoms provide a window into autoimmune vasculopathy, Dr. Eichenfield said.

The disease is typically associated with progressive symmetric involvement of the proximal musculature. Gowers' sign, difficulty climbing stairs, arising from chairs, and combing hair—as well as muscle enzyme elevations, arrhythmia, dyspnea, dysphonia, and dysphagia—may be observed and should be assessed in the review of systems.

Neonatal Lupus Erythematosus

Dr. Eichenfield also described neonatal lupus erythematosus, which typically presents within the first 12 weeks of an infant's life with scaling and facial eruptions that may be mistaken for tinea.

Because of the associated cardiac, hepatic, hematologic, and central nervous system considerations, a full work-up for accurate diagnosis is essential.

The work-up should include a head circumference measure; serological testing for renal function, cytopenia, liver enzyme elevations, antinuclear antibody, anti-dsDNA, anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B; electrocardiography; and, potentially, a skin biopsy, he noted. Examples of other systemic conditions that may present with skin signs in children and young adults include minocycline-induced autoimmunity, psoriasis, and pediatric morphea, according to Dr. Eichenfield.

He reported that he did not have any conflicts of interest in regards to his presentation. SDEF and this news organization are owned by Elsevier.

This CT image shows extensive soft-tissue calcifications in dermatomyo-sitis, largely in the subcutan-eous gluteal fat (arrowheads) in this 19-year-old female with severe multisystemic involvement.

Source ©Elsevier

Arthritis or arthralgia occurs in up to 85% of Henoch-Schönlein cases, renal damage in up to 60%.

Source Dr. Eichenfield

Barium enema postevacuation film shows marginal filling defects in the distal ileum in Henoch-Schönlein.

Source ©Elsevier

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized, according to an analysis of NHANES.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for American adults aged 25-75 years during 1971-1975, 1976-1980, 1988-1994, and 1999-2004, and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey to 10.5% by the third survey, but then decreased to 7.5% in the fourth survey (1999-2004).

The low-risk-factor profile incorporated the following variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. According to the results, “fewer than 10% of Americans are meeting the low-risk goals.”

The low-risk factor patterns were similar for men and women, but the prevalence of low-risk profiles was higher in women than in men in each of the surveys, the authors reported. Similarly, the low-risk-factor burden was much higher among survey respondents aged 25-44 years than among those aged 45-64 or 65-74 years in all the surveys, and it was higher among whites than blacks during each survey except 1976-1980. During 1988-1994 and 1999-2004 only, a larger percentage of whites had a low-risk-factor burden compared with Mexican Americans, they wrote.

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%, respectively). For blood pressure, the low-risk percentage was higher for the period 1988-1994 than for the 1971-1975 period, but it decreased for the period 1999-2004, “which is worrisome,” the authors wrote.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

Because the NHANES surveyed only noninstitutionalized adults, the true risk-factor burdens “may be even worse” than those reported, which is one of the limitations of the study, the authors noted. Additional limitations include the exclusion of physical activity and a dietary index as part of the risk determination, and changes in the wording of questions for use of current antihypertensive medication and physician-diagnosed diabetes that could potentially have affected the estimates, they wrote.

Despite the possible limitations, “our results clearly demonstrate a great need for prevention; thus, health care providers should have adequate resources, time, and reimbursement to engage in the prevention of cardiovascular disease in individuals,” the authors wrote.

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health, Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, said that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia” (Circulation 2009 [doi:10.1161/CIRCULATIONAHA.109.891507]).

The authors reported having no financial disclosures related to this report.

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized, according to an analysis of NHANES.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for American adults aged 25-75 years during 1971-1975, 1976-1980, 1988-1994, and 1999-2004, and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey to 10.5% by the third survey, but then decreased to 7.5% in the fourth survey (1999-2004).

The low-risk-factor profile incorporated the following variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. According to the results, “fewer than 10% of Americans are meeting the low-risk goals.”

The low-risk factor patterns were similar for men and women, but the prevalence of low-risk profiles was higher in women than in men in each of the surveys, the authors reported. Similarly, the low-risk-factor burden was much higher among survey respondents aged 25-44 years than among those aged 45-64 or 65-74 years in all the surveys, and it was higher among whites than blacks during each survey except 1976-1980. During 1988-1994 and 1999-2004 only, a larger percentage of whites had a low-risk-factor burden compared with Mexican Americans, they wrote.

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%, respectively). For blood pressure, the low-risk percentage was higher for the period 1988-1994 than for the 1971-1975 period, but it decreased for the period 1999-2004, “which is worrisome,” the authors wrote.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

Because the NHANES surveyed only noninstitutionalized adults, the true risk-factor burdens “may be even worse” than those reported, which is one of the limitations of the study, the authors noted. Additional limitations include the exclusion of physical activity and a dietary index as part of the risk determination, and changes in the wording of questions for use of current antihypertensive medication and physician-diagnosed diabetes that could potentially have affected the estimates, they wrote.

Despite the possible limitations, “our results clearly demonstrate a great need for prevention; thus, health care providers should have adequate resources, time, and reimbursement to engage in the prevention of cardiovascular disease in individuals,” the authors wrote.

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health, Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, said that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia” (Circulation 2009 [doi:10.1161/CIRCULATIONAHA.109.891507]).

The authors reported having no financial disclosures related to this report.

The prevalence of a low-risk profile for cardiovascular disease among adults in the U.S. population has decreased in recent years, suggesting the “huge potential” for preventing cardiovascular disease is far from being realized, according to an analysis of NHANES.

Using data from four National Health and Nutrition Examination Surveys, Dr. Earl S. Ford, medical officer of the U.S. Public Health Service at the Centers for Disease Control and Prevention in Atlanta, and colleagues tracked cardiovascular risk data for American adults aged 25-75 years during 1971-1975, 1976-1980, 1988-1994, and 1999-2004, and showed that the prevalence of a low-risk profile increased from 4.4% at the time of the first survey to 10.5% by the third survey, but then decreased to 7.5% in the fourth survey (1999-2004).

The low-risk-factor profile incorporated the following variables: not currently smoking; total cholesterol less than 200 mg/dL without cholesterol-lowering medications; systolic blood pressure less than 120 mm Hg and diastolic blood pressure less than 80 mm Hg without antihypertensive medications; body mass index less than 25 kg/m

“The limited strides that were made toward achieving low-risk status during the 1970s and 1980s have more recently been negated by the obesity epidemic and increased rates of hypertension and diabetes,” Dr. Ford said in an interview. According to the results, “fewer than 10% of Americans are meeting the low-risk goals.”

The low-risk factor patterns were similar for men and women, but the prevalence of low-risk profiles was higher in women than in men in each of the surveys, the authors reported. Similarly, the low-risk-factor burden was much higher among survey respondents aged 25-44 years than among those aged 45-64 or 65-74 years in all the surveys, and it was higher among whites than blacks during each survey except 1976-1980. During 1988-1994 and 1999-2004 only, a larger percentage of whites had a low-risk-factor burden compared with Mexican Americans, they wrote.

An analysis of the individual risk categories showed favorable trends for not currently smoking (60% at the time of the first survey and 74% by the fourth survey) and low concentrations of total cholesterol (35% and 43%, respectively). For blood pressure, the low-risk percentage was higher for the period 1988-1994 than for the 1971-1975 period, but it decreased for the period 1999-2004, “which is worrisome,” the authors wrote.

Similarly, “the distribution of body mass index progressively deteriorated over time,” they reported, adding that the unfavorable trends “argue for vigorous population-based approaches to reverse the unhealthy shift in the distributions of blood pressure and body mass index and to sustain or accelerate the improvement in the distribution of total cholesterol.”

Because the NHANES surveyed only noninstitutionalized adults, the true risk-factor burdens “may be even worse” than those reported, which is one of the limitations of the study, the authors noted. Additional limitations include the exclusion of physical activity and a dietary index as part of the risk determination, and changes in the wording of questions for use of current antihypertensive medication and physician-diagnosed diabetes that could potentially have affected the estimates, they wrote.

Despite the possible limitations, “our results clearly demonstrate a great need for prevention; thus, health care providers should have adequate resources, time, and reimbursement to engage in the prevention of cardiovascular disease in individuals,” the authors wrote.

In an accompanying editorial, Rob M. van Dam, Ph.D., of the Harvard School of Public Health, Boston, and Dr. Walter C. Willett of Brigham and Women's Hospital in Boston, said that the trajectory of the risk factor trends is even more worrisome considering the analyses “do not yet reflect the effects of the current epidemic of childhood obesity, which causes an early onset of type 2 diabetes, hypertension, and dyslipidemia” (Circulation 2009 [doi:10.1161/CIRCULATIONAHA.109.891507]).

The authors reported having no financial disclosures related to this report.

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

"Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk," Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781-6).

Further, Merck's marketing strategy included awarding "sizeable educational grants" to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. "We did not require any reporting or review of any materials developed," Ms. Eisele said. "Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences."

"We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals," said Ms. Eisele. "Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education."

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine "is cause for concern."

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

The ASCCP's member clinicians "have little occasion to recommend or deliver immunization," and could potentially see a negative economic benefit from a successful vaccination effort, yet "ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset," and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

"That is not the case," Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, said in an interview. "We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year."

Given the potential for conflicts of interest associated with an industry-supported educational program, "we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently," Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO) and the American College Health Association.

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard from a surgically-based to a medically-based discipline. The organization used the funding from Merck and other companies to create an education campaign, which was overseen by a panel that included some members with financial ties to Merck.

The materials created by the SGO panel "omitted cautionary qualifications," according to Dr. Rothman and Dr. Rothman. Further, the materials "did not include data on disparities in cervical cancer incidence and outcomes," nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

The ACHA used grant money to create an HPV Vaccine Toolkit for clinicians that includes talking points, sample e-mail messages, sample press releases, and public service announcements—none of which mention funding, according to the Dr. Rothman and Dr. Rothman. ACHA officials could not be reached for comment.

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

"Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk," Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781-6).

Further, Merck's marketing strategy included awarding "sizeable educational grants" to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. "We did not require any reporting or review of any materials developed," Ms. Eisele said. "Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences."

"We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals," said Ms. Eisele. "Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education."

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine "is cause for concern."

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

The ASCCP's member clinicians "have little occasion to recommend or deliver immunization," and could potentially see a negative economic benefit from a successful vaccination effort, yet "ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset," and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

"That is not the case," Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, said in an interview. "We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year."

Given the potential for conflicts of interest associated with an industry-supported educational program, "we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently," Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO) and the American College Health Association.

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard from a surgically-based to a medically-based discipline. The organization used the funding from Merck and other companies to create an education campaign, which was overseen by a panel that included some members with financial ties to Merck.

The materials created by the SGO panel "omitted cautionary qualifications," according to Dr. Rothman and Dr. Rothman. Further, the materials "did not include data on disparities in cervical cancer incidence and outcomes," nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

The ACHA used grant money to create an HPV Vaccine Toolkit for clinicians that includes talking points, sample e-mail messages, sample press releases, and public service announcements—none of which mention funding, according to the Dr. Rothman and Dr. Rothman. ACHA officials could not be reached for comment.

Women at the highest risk for human papillomavirus infection were among the least likely to get the message that there is a vaccine that can protect them, editorialists said in a special communication published in JAMA.

Sheila M. Rothman, Ph.D., and David J. Rothman, Ph.D., of Columbia University, New York, contend that Merck & Co. promoted its quadrivalent human papillomavirus vaccine Gardasil as an anticancer agent, maximizing the threat of cervical cancer and minimizing the sexual transmission of the virus.

"Rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African Americans in the South, Latinos along the Texas-Mexico border, and whites in Appalachia, the marketing campaign posited that every girl was at equal risk," Dr. Rothman and Dr. Rothman wrote (JAMA 2009;302:781-6).

Further, Merck's marketing strategy included awarding "sizeable educational grants" to professional medical associations in adolescent and women's health and oncology to encourage these organizations to undertake or intensify vaccination activities, according to the authors.

In an interview, Pamela Eisele, a spokeswoman for Merck, denied the claims. "We did not require any reporting or review of any materials developed," Ms. Eisele said. "Merck provides independent grant support to professional medical associations that develop and distribute their own educational information about HPV and cervical cancer to broad audiences."

"We value our relationships with these groups and conduct our interactions with strict adherence to the Pharmaceutical Research and Manufacturers of America Code on Interactions with Healthcare Professionals," said Ms. Eisele. "Merck closely follows the standards for commercial support of continuing medical education established by the Accreditation Council for Continuing Medical Education."

Dr. Rothman and Dr. Rothman charged that the role of several professional medical associations in the marketing of the HPV vaccine "is cause for concern."

One recipient of Merck funding, the American Society for Colposcopy and Cervical Pathology (ASCCP), used the grant money to create a day-long program to educate its members on vaccine use. Further, the society developed a Gardasil-specific speaker support center that included a registry of members who completed the educational program and a database of when and where they presented, Dr. Rothman and Dr. Rothman said.

The ASCCP's member clinicians "have little occasion to recommend or deliver immunization," and could potentially see a negative economic benefit from a successful vaccination effort, yet "ASCCP leaders perceived vaccine promotion as an opportunity to turn a potential financial liability into an asset," and to re-energize its society, according to Dr. Rothman and Dr. Rothman.

"That is not the case," Dr. L. Stewart Massad, chair of ASCCP's Practice and Ethics committees, said in an interview. "We have long recognized that the current [cervical cancer] prevention system is flawed. Although prevention based on Pap testing, colposcopy, and destruction of precursors is effective, it is expensive, intrusive, insensitive, and nonspecific, and it results in the overtreatment of thousands of women each year."

Given the potential for conflicts of interest associated with an industry-supported educational program, "we set up internal systems to evaluate the materials for bias, and I reviewed all of the materials independently," Dr. Massad said, noting that he accepts no financial support or grant money.

Merck also gave grant money to the Society of Gynecologic Oncologists (SGO) and the American College Health Association.

Dr. Rothman and Dr. Rothman wrote that the SGO was concerned about its future as a subspecialty and perceived the HPV marketing opportunity as a way to springboard from a surgically-based to a medically-based discipline. The organization used the funding from Merck and other companies to create an education campaign, which was overseen by a panel that included some members with financial ties to Merck.

The materials created by the SGO panel "omitted cautionary qualifications," according to Dr. Rothman and Dr. Rothman. Further, the materials "did not include data on disparities in cervical cancer incidence and outcomes," nor did it include questions about the vaccine's history and efficacy, whether the risks outweigh the benefits, or a discussion of the continued need for Pap tests.

The ACHA used grant money to create an HPV Vaccine Toolkit for clinicians that includes talking points, sample e-mail messages, sample press releases, and public service announcements—none of which mention funding, according to the Dr. Rothman and Dr. Rothman. ACHA officials could not be reached for comment.

BOSTON — Establishing a treatment protocol and seeking the collaboration of cardiologists who treat children may limit the potential for serious complications associated with the off-label use of propranolol for the treatment of severe infantile hemangiomas, according to Dr. Elaine C. Siegfried.

In her own practice, Dr. Siegfried, professor of pediatrics and dermatology at St. Louis University, has developed such a protocol. However, she said she continues to use first-line prednisolone for infants with severe hemangiomas.

Prednisolone "really is the path of least resistance, and it's the treatment we know the most about," said Dr. Siegfried. "For children who don't respond to the prednisolone or who cannot tolerate it, I consider propranolol."

Interest in the treatment rose after a report of serendipitous improvement of severe hemangiomas in two infants treated with propranolol for cardiac arrhythmias and hypertension as well as good responses in nine infants who were subsequently treated with propranolol alone (N. Engl. J. Med. 2008;358:2649-51).

Although the report was "the most exciting news in pediatric dermatology in the past year," there are limited data about propranolol's potential risks as well as about best practices for initiating and monitoring the therapy for this unapproved indication, Dr. Siegfried said at the American Academy of Dermatology's Academy 2009 meeting.

Before using propranolol for severe hemangiomas, "work with the subspecialists who know the most about the drug and come up with a consensus approach to using it," she recommended.

The treatment protocol developed by Dr. Siegfried and her colleagues includes obtaining a baseline pulse, respiration rates, blood pressure measurement, and echocardiography and 48-hour monitoring (inpatient or outpatient with home nursing visits) of vital signs and blood glucose levels. An initial propranolol dose of 0.16 mg/kg of body weight is given every 8 hours and doubled incrementally to a maximum of 0.67 mg/kg (a maximum daily dose of 2 mg/kg), as long as vital signs and glucose levels remain normal, she said, noting that the drug is gradually tapered over a 2-week period.

Reports of complications have included hypothermia and bradycardia—known side effects of propranolol—and subclinical hypoglycemia, according to Dr. Siegfried. She and her associates noted their concerns about complications and protocols in a letter written in response to the original publication (N. Engl. J. Med. 2008;359:2846-7).

Parents need to be carefully trained regarding administration of the drug. The formulation is highly concentrated, and children need to be fed frequently to prevent hypoglycemia, Dr. Siegfried said. "Sustained hypoglycemia has been associated with long-term neurodevelopmental outcomes." Further, the clinical features of complications such as tachypnea, jitteriness, and hypohidrosis can be blunted by propranolol.

Complication risks could be high in infants with large hemangiomas and in those with miliary hemangiomatosis, which puts them at risk for high-output cardiac compromise. Infants with PHACES syndrome have arterial abnormalities that put them at risk for hypo-perfusion and ischemic infarct. There have been no reports of propranolol complications in infants with PHACES, "but it's something you have to watch," she said.

Close monitoring is critical in high-risk subsets, Dr. Siegfried said. In infants with hemangiomatosis, for example, "you want to look very closely at the hepatic artery and portal vein [via abdominal ultrasound] because dilatation can be an early sign of cardiac compromise." In infants with PHACES syndrome, propranolol "may be absolutely contraindicated" if there is evidence of arterial hyperplasia or stenosis. Additional studies are probably warranted before the drug can be used in this population.

A multicenter, prospective trial is planned to address the efficacy, risks, and appropriate use of propranolol in patients with infantile hemangioma; Dr. Siegfried disclosed that she will be a principal investigator.

BOSTON — Establishing a treatment protocol and seeking the collaboration of cardiologists who treat children may limit the potential for serious complications associated with the off-label use of propranolol for the treatment of severe infantile hemangiomas, according to Dr. Elaine C. Siegfried.

In her own practice, Dr. Siegfried, professor of pediatrics and dermatology at St. Louis University, has developed such a protocol. However, she said she continues to use first-line prednisolone for infants with severe hemangiomas.

Prednisolone "really is the path of least resistance, and it's the treatment we know the most about," said Dr. Siegfried. "For children who don't respond to the prednisolone or who cannot tolerate it, I consider propranolol."

Interest in the treatment rose after a report of serendipitous improvement of severe hemangiomas in two infants treated with propranolol for cardiac arrhythmias and hypertension as well as good responses in nine infants who were subsequently treated with propranolol alone (N. Engl. J. Med. 2008;358:2649-51).

Although the report was "the most exciting news in pediatric dermatology in the past year," there are limited data about propranolol's potential risks as well as about best practices for initiating and monitoring the therapy for this unapproved indication, Dr. Siegfried said at the American Academy of Dermatology's Academy 2009 meeting.

Before using propranolol for severe hemangiomas, "work with the subspecialists who know the most about the drug and come up with a consensus approach to using it," she recommended.

The treatment protocol developed by Dr. Siegfried and her colleagues includes obtaining a baseline pulse, respiration rates, blood pressure measurement, and echocardiography and 48-hour monitoring (inpatient or outpatient with home nursing visits) of vital signs and blood glucose levels. An initial propranolol dose of 0.16 mg/kg of body weight is given every 8 hours and doubled incrementally to a maximum of 0.67 mg/kg (a maximum daily dose of 2 mg/kg), as long as vital signs and glucose levels remain normal, she said, noting that the drug is gradually tapered over a 2-week period.

Reports of complications have included hypothermia and bradycardia—known side effects of propranolol—and subclinical hypoglycemia, according to Dr. Siegfried. She and her associates noted their concerns about complications and protocols in a letter written in response to the original publication (N. Engl. J. Med. 2008;359:2846-7).

Parents need to be carefully trained regarding administration of the drug. The formulation is highly concentrated, and children need to be fed frequently to prevent hypoglycemia, Dr. Siegfried said. "Sustained hypoglycemia has been associated with long-term neurodevelopmental outcomes." Further, the clinical features of complications such as tachypnea, jitteriness, and hypohidrosis can be blunted by propranolol.

Complication risks could be high in infants with large hemangiomas and in those with miliary hemangiomatosis, which puts them at risk for high-output cardiac compromise. Infants with PHACES syndrome have arterial abnormalities that put them at risk for hypo-perfusion and ischemic infarct. There have been no reports of propranolol complications in infants with PHACES, "but it's something you have to watch," she said.

Close monitoring is critical in high-risk subsets, Dr. Siegfried said. In infants with hemangiomatosis, for example, "you want to look very closely at the hepatic artery and portal vein [via abdominal ultrasound] because dilatation can be an early sign of cardiac compromise." In infants with PHACES syndrome, propranolol "may be absolutely contraindicated" if there is evidence of arterial hyperplasia or stenosis. Additional studies are probably warranted before the drug can be used in this population.

A multicenter, prospective trial is planned to address the efficacy, risks, and appropriate use of propranolol in patients with infantile hemangioma; Dr. Siegfried disclosed that she will be a principal investigator.

BOSTON — Establishing a treatment protocol and seeking the collaboration of cardiologists who treat children may limit the potential for serious complications associated with the off-label use of propranolol for the treatment of severe infantile hemangiomas, according to Dr. Elaine C. Siegfried.

In her own practice, Dr. Siegfried, professor of pediatrics and dermatology at St. Louis University, has developed such a protocol. However, she said she continues to use first-line prednisolone for infants with severe hemangiomas.

Prednisolone "really is the path of least resistance, and it's the treatment we know the most about," said Dr. Siegfried. "For children who don't respond to the prednisolone or who cannot tolerate it, I consider propranolol."

Interest in the treatment rose after a report of serendipitous improvement of severe hemangiomas in two infants treated with propranolol for cardiac arrhythmias and hypertension as well as good responses in nine infants who were subsequently treated with propranolol alone (N. Engl. J. Med. 2008;358:2649-51).

Although the report was "the most exciting news in pediatric dermatology in the past year," there are limited data about propranolol's potential risks as well as about best practices for initiating and monitoring the therapy for this unapproved indication, Dr. Siegfried said at the American Academy of Dermatology's Academy 2009 meeting.

Before using propranolol for severe hemangiomas, "work with the subspecialists who know the most about the drug and come up with a consensus approach to using it," she recommended.

The treatment protocol developed by Dr. Siegfried and her colleagues includes obtaining a baseline pulse, respiration rates, blood pressure measurement, and echocardiography and 48-hour monitoring (inpatient or outpatient with home nursing visits) of vital signs and blood glucose levels. An initial propranolol dose of 0.16 mg/kg of body weight is given every 8 hours and doubled incrementally to a maximum of 0.67 mg/kg (a maximum daily dose of 2 mg/kg), as long as vital signs and glucose levels remain normal, she said, noting that the drug is gradually tapered over a 2-week period.

Reports of complications have included hypothermia and bradycardia—known side effects of propranolol—and subclinical hypoglycemia, according to Dr. Siegfried. She and her associates noted their concerns about complications and protocols in a letter written in response to the original publication (N. Engl. J. Med. 2008;359:2846-7).

Parents need to be carefully trained regarding administration of the drug. The formulation is highly concentrated, and children need to be fed frequently to prevent hypoglycemia, Dr. Siegfried said. "Sustained hypoglycemia has been associated with long-term neurodevelopmental outcomes." Further, the clinical features of complications such as tachypnea, jitteriness, and hypohidrosis can be blunted by propranolol.

Complication risks could be high in infants with large hemangiomas and in those with miliary hemangiomatosis, which puts them at risk for high-output cardiac compromise. Infants with PHACES syndrome have arterial abnormalities that put them at risk for hypo-perfusion and ischemic infarct. There have been no reports of propranolol complications in infants with PHACES, "but it's something you have to watch," she said.

Close monitoring is critical in high-risk subsets, Dr. Siegfried said. In infants with hemangiomatosis, for example, "you want to look very closely at the hepatic artery and portal vein [via abdominal ultrasound] because dilatation can be an early sign of cardiac compromise." In infants with PHACES syndrome, propranolol "may be absolutely contraindicated" if there is evidence of arterial hyperplasia or stenosis. Additional studies are probably warranted before the drug can be used in this population.

A multicenter, prospective trial is planned to address the efficacy, risks, and appropriate use of propranolol in patients with infantile hemangioma; Dr. Siegfried disclosed that she will be a principal investigator.

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

BOSTON — The threshold for biopsying unexplained nail dystrophy or discoloration should be low, according to Dr. Phoebe Rich.

Although the majority of nail unit lesions are benign, "malignancies are not as obvious to spot clinically as you would think," and a missed or delayed diagnosis can be life threatening, Dr. Rich said at the American Academy of Dermatology's Academy 2009 meeting.

Any unexplained solitary, painful, dystrophic nail, particularly in an elderly patient, should be biopsied to rule out squamous cell carcinoma of the nail bed.

Any pigmented band of unknown etiology, especially in white patients, requires a biopsy to rule out melanoma, said Dr. Rich of the department of dermatology at Oregon Health and Science University in Portland.

The presence of certain clinical signs and symptoms can offer clues to the diagnosis of malignant neoplasms. For example, Dr. Rich said, squamous cell carcinoma of the nail may present as longitudinal erythronychia (a pinkish band extending from the nail matrix); as a nodule or tumor with or without nail loss; as a wartlike periungual lesion with nail splitting and skin fissure; or as a draining subungual mass. Because these presentations mimic other clinical entities, "you have to biopsy to get an accurate diagnosis," she said, stressing that nail surgery should not be intimidating. "Any dermatologist who can do a punch biopsy can do a nail biopsy."

For the aforementioned lesions, "you can take a punch or a shave [nail bed] biopsy, and once you have a diagnosis, you can refer the patient for Mohs or, if you feel confident, you can remove it yourself," said Dr. Rich. "We all do skin surgery for squamous cell carcinoma day in and day out. When you remove it, you just have to remember that there is no subcutaneous tissue in the nail, so you are actually removing it at the level just at the periosteum. Check to make sure you have got a nice margin, and you're in good shape."

Subungual melanoma arises from the nail matrix and often presents initially as longitudinal melanonychia, said Dr. Rich. The differential diagnosis for melanonychia is broad, however, and includes benign nevi, lentigo in the nail matrix, genetic and ethnic-type pigmentation, subungual hematoma, drug-induced pigmentation, vitamin deficiency fungal infections, and squamous cell carcinoma in situ, she said.

A high index of suspicion for melanoma should exist with lesions that begin under the nail and extend outward onto healthy skin around the nail (Hutchinson's sign); if there is variability in the pigmentation of the band; if the pigmented band is widening or growing; or if there is bleeding or signs of ulceration, Dr. Rich explained. "In these cases, when you have a pigmented band, you have to open it up, look in there, and get a specimen," she said. "It's critical that you biopsy proximally at the matrix, at the origin of the band, because you need the melanocytes. If you biopsy the nail bed distally in an area where the nail plate is involved, you're not going to get the pigment, and you won't get an accurate diagnosis."

Although pigmentary changes can offer a clue to the presence of melanoma, a certain percentage of nail melanomas are amelanotic, said Dr. Rich. Amelanotic melanomas of the nail bed may resemble chronic paronychia or other benign nail conditions, she said.

For suspected nail melanoma, a nail matrix shave biopsy is sufficient, "unless you suspect advanced melanoma, which is characterized clinically by a dystrophic nail plate in addition to the pigmentation," Dr. Rich said. "In that case, a full thickness biopsy is needed." For large lesions located in the lateral third of the nail, "a longitudinal nail biopsy yields the best information because it samples the nail matrix, nail bed, nail fold, and hyponychium."

Proper preparation of the specimen is also critical to an accurate diagnosis, stressed Dr. Rich, who always orients the specimen on a paper template with a schematic of the nail and fingertip to duplicate its position on the nail unit before dropping it into formalin. "This way, the pathologist knows where the sample comes from," she said.

Because patients are typically apprehensive about nail surgery, the onus is on the clinician to reassure them that it can be done painlessly by using appropriate and effective anesthesia, according to Dr. Rich, who often begins the anesthesia application by having the patient—especially if it is a child—hold a vibrating device. This offers a distraction, she explained, and provides a competing sensation. She then administers an ethyl chloride spray, followed by an injection, via a 30-gauge needle, of lidocaine with epinephrine—which has been proved safe. The addition of bupivacaine or ropivacaine helps to minimize postoperative discomfort.

The anesthesia can be administered using a true digital block, which involves injecting the anesthetic agent into the lateral base of the digit, or through a wing block, whereby the agent is injected into the proximal nail fold. "In my experience, a wing block is quicker, and because it requires a smaller volume of anesthesia, it is safer," said Dr. Rich. "It is also much less painful than a digital block."

Dr. Rich has received advisory board honoraria from Abbott Laboratories and investigator grants from Centocor Inc., Wyeth, and Genentech Inc.

Subungual melanoma often presents initially as longitudinal melanonychia.

Source ©dermnet.com

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which focus specifically on clinical diagnosis vs. classification, distinguishing them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England), lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a EULAR task force of 17 osteoarthritis experts from 12 European countries, explained Dr. Zhang.

A systematic literature search was undertaken to identify the best available research evidence to support the various propositions; the strength of recommendation for each diagnostic consideration was based on research evidence and clinical expertise, according to Dr. Zhang. The diagnostic accuracy of the recommendations was tested using multiple predictive models in two populations, including one each from the Netherlands and the United Kingdom, he explained.

Among the recommendations, risk factors emerged as an important consideration for identifying patients with knee pain in whom knee OA is the most likely diagnosis, Dr. Zhang and his colleagues determined. The risk factors that are strongly associated with the incidence of knee OA include increasing age older than 50 years, female sex, higher body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, they wrote.

The EULAR task force also determined that plain radiography of the knee (including a weight-bearing, a semiflexed, and lateral and skyline views) continues to be the clinical standard imaging modality for morphologic assessment of knee OA, but noted that it is an adjunct rather than a central feature for diagnostic purposes. They also observed that other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the recommendations. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, OA subsets, typical symptoms and signs, the use of laboratory tests, and differential diagnosis.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies.

Dr. Zhang reported having no relevant financial relationships to disclose.

EULAR considers x-rays unnecessary in patients older than 40 years of age.

Source ©DR. P. MARAZZI/PHOTO RESEARCHERS, INC.

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which focus specifically on clinical diagnosis vs. classification, distinguishing them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England), lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a EULAR task force of 17 osteoarthritis experts from 12 European countries, explained Dr. Zhang.

A systematic literature search was undertaken to identify the best available research evidence to support the various propositions; the strength of recommendation for each diagnostic consideration was based on research evidence and clinical expertise, according to Dr. Zhang. The diagnostic accuracy of the recommendations was tested using multiple predictive models in two populations, including one each from the Netherlands and the United Kingdom, he explained.

Among the recommendations, risk factors emerged as an important consideration for identifying patients with knee pain in whom knee OA is the most likely diagnosis, Dr. Zhang and his colleagues determined. The risk factors that are strongly associated with the incidence of knee OA include increasing age older than 50 years, female sex, higher body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, they wrote.

The EULAR task force also determined that plain radiography of the knee (including a weight-bearing, a semiflexed, and lateral and skyline views) continues to be the clinical standard imaging modality for morphologic assessment of knee OA, but noted that it is an adjunct rather than a central feature for diagnostic purposes. They also observed that other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the recommendations. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, OA subsets, typical symptoms and signs, the use of laboratory tests, and differential diagnosis.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies.

Dr. Zhang reported having no relevant financial relationships to disclose.

EULAR considers x-rays unnecessary in patients older than 40 years of age.

Source ©DR. P. MARAZZI/PHOTO RESEARCHERS, INC.

A confident diagnosis of knee osteoarthritis can be made without radiographic examination in adults older than 40 years based on criteria described in evidence-based recommendations to be published by the European League Against Rheumatism.

The criteria include usage-related knee pain, short-lived morning stiffness, functional limitation, and one or more “typical” examination findings, such as crepitus, restricted movement, and bony enlargement.

Clinical signs, symptoms, risk factors, and plain radiography are the cornerstones of the recommendations, which focus specifically on clinical diagnosis vs. classification, distinguishing them from the American College of Rheumatology criteria, said Weiya Zhang, Ph.D., of the University of Nottingham (England), lead author of the recommendations, which were presented at the annual European Congress of Rheumatology in Copenhagen and are slated for publication in upcoming issue of the Annals of Rheumatic Disease.

The recommendations were developed by a EULAR task force of 17 osteoarthritis experts from 12 European countries, explained Dr. Zhang.

A systematic literature search was undertaken to identify the best available research evidence to support the various propositions; the strength of recommendation for each diagnostic consideration was based on research evidence and clinical expertise, according to Dr. Zhang. The diagnostic accuracy of the recommendations was tested using multiple predictive models in two populations, including one each from the Netherlands and the United Kingdom, he explained.

Among the recommendations, risk factors emerged as an important consideration for identifying patients with knee pain in whom knee OA is the most likely diagnosis, Dr. Zhang and his colleagues determined. The risk factors that are strongly associated with the incidence of knee OA include increasing age older than 50 years, female sex, higher body mass index, previous knee injury or malalignment, joint laxity, occupational or recreational usage, family history, and the presence of Heberden's nodes, they wrote.

The EULAR task force also determined that plain radiography of the knee (including a weight-bearing, a semiflexed, and lateral and skyline views) continues to be the clinical standard imaging modality for morphologic assessment of knee OA, but noted that it is an adjunct rather than a central feature for diagnostic purposes. They also observed that other imaging modalities, such as MRI, sonography, and scintigraphy, are “seldom indicated for diagnosis of OA,” according to the recommendations. Classic radiographic features “are focal joint space narrowing, osteophyte, subchondral bone sclerosis, and subchondral cysts.”

Other recommendations cover the definition of knee OA, OA subsets, typical symptoms and signs, the use of laboratory tests, and differential diagnosis.

The authors acknowledged that the recommendations are limited because they were derived from literature based on different studies.

Dr. Zhang reported having no relevant financial relationships to disclose.

EULAR considers x-rays unnecessary in patients older than 40 years of age.

Source ©DR. P. MARAZZI/PHOTO RESEARCHERS, INC.

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15–25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy. In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant women has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said. With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

Dr. Kimball has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and has a fellowship funded by Centocor.

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15–25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy. In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant women has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said. With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

Dr. Kimball has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and has a fellowship funded by Centocor.

BOSTON — Data suggesting that pregnant women with psoriasis have poorer outcomes than those without it highlight the need for more research to determine whether the outcome discrepancies are a function of the disease itself, comorbidities, or treatment side effects, according to Dr. Alexa Boer Kimball.

“We know that pregnancy can have an impact on psoriasis—studies have shown that about 50% of women report improvements; 15–25% worsen; and the rest don't change—but we know less about the effect of psoriasis on pregnancy,” said Dr. Kimball of the department of dermatology at Harvard Medical School in Boston.

In a case-control study of 145 live births in women with psoriasis between 1998 and 2004, investigators at Ben Gurion University of the Negev in Beer-Sheva, Israel, demonstrated an association between pregnancy complications and psoriasis. Specifically, recurrent abortions and chronic hypertension were significantly associated with psoriasis in a multivariate analysis, and psoriasis was an independent risk factor for cesarean delivery (J. Reprod. Med. 2008;53:183–7).

“The findings are not really surprising when you think about the [inflammatory bowel disease] literature and the lupus literature, for example. It's clear that systemic autoimmune diseases can have adverse effects on pregnancies,” Dr. Kimball said at the American Academy of Dermatology's Academy 2009 meeting.

“Unfortunately, our knowledge about pregnancy outcomes in psoriasis is very limited, which in turn limits the treatment guidance that we can offer.” This is due, she said, to the dearth of literature on the topic, the exclusion of pregnant women from most clinical trials, and the low enrollment in pregnancy registries.

Further, said Dr. Kimball, the various regulatory agencies are not consistent in interpreting numerical data regarding drug safety in pregnancy. In one study comparing the pregnancy risk classification of 236 commonly used drugs by three international regulatory agencies—the U.S. Food and Drug Administration, the Australian Drug Evaluation Committee, and the Swedish Catalogue of Approved Drugs—only 26% of the drugs were placed into the same risk category, she said (Drug Saf. 2000;23:245–53).

“Theoretically, these groups should be looking at the same data and arriving at essentially the same conclusions. The fact that they're not tells you that there is a substantial subjective review component to how we evaluate this information,” she said.

For these reasons, providing therapeutic guidance to pregnant women with psoriasis is “incredibly challenging,” Dr. Kimball said. The challenge is exacerbated by several social and environmental considerations, including the fact that “women today are under extraordinary pressure not to expose their babies to unknown and unnecessary risks, which may make them more likely to forego therapy that they might actually need,” she said. “In counseling these patients, there really obviously has to be a very open communication about that, although you really can't make the choice for them. It's a very personal decision about the risks they're willing to take.”

Similarly, there is tremendous pressure on women to breastfeed for long periods of time, which can also have an impact on treatment decisions. “A woman may decide to hold off on treatment while she's breastfeeding, and again that's a personal decision, but recognize that it may be a really substantial sacrifice, and in cases of psoriatic arthritis in particular, it may not be all that good for them over time,” she said.

In addition to helping patients determine how to proceed with treatment once they are pregnant, patient counseling should address exposures that might have already happened. “The critical period in all pregnancies for fetal malformations is early, in the first trimester, and lots of women are exposed to drugs before they even know they're pregnant,” said Dr. Kimball.

“In situations involving major risks, referral to a genetics counselor can be useful, but it's also important to remind patients that, under the best of circumstances, not all pregnancies turn out perfectly. The developmental disorder rate [in the general population] is about 3% at birth and about 8% by age 5. It's important to give that information to women so they don't feel overly guilty about the choices they're making,” she said.

“So what can we actually recommend?” Dr. Kimball asked. “For first-line therapy, moisturizers can be used with reckless abandon, and low-potency topical steroids have been determined to not be a risk.” Systemic steroids, on the other hand, should be avoided in the first trimester because of the association with cleft palate, she said.

The second-line treatment algorithm includes narrow band ultraviolet B (UVB) phototherapy, if feasible, “but this may be a challenge if, for example, the pregnant women has other kids at home or just doesn't have the flexibility in terms of scheduling,” Dr. Kimball said. “Home UVB is an option, and tanning beds—although problematic for other reasons—in a severe patient might be worth considering if they really have no other options.”

Concern regarding the possibility that folate levels might be affected by light therapy, Dr. Kimball noted, has been put to rest by a new study showing that UVB phototherapy does not influence serum and red cell folate levels in psoriasis (J. Am. Acad. Dermatol. 2009;61:259–62).

The question of heat exposure has not been addressed, however. “There are recommendations against hot tubs and hot baths in the first trimester, for example, because of potential injury to the fetus, so if you have someone way up on the light scale, that might be something worth thinking about.”

Tumor necrosis factor inhibitors fall under third-line therapies. “Obviously we have limited data on these. They are generally risk category B, so most people feel reasonably comfortable if we had to go that direction, but there are potential risks that are unclear,” Dr. Kimball said.

Cyclosporine, which was the therapy of choice prior to the biologics era, is another third-line treatment, said Dr. Kimball. “Although cyclosporine is [risk] category C, we probably have the best information about this drug due to the transplant registries that are out there,” she noted.

It is associated with a low birth rate and prematurity, “so there are known risks associated with it, but malformations do not seem to be an issue.” Systemic steroids in the second and third trimester would be another third-line option if needed, she said.

Among the systemic therapies to avoid in pregnancy are PUVA, which can potentially lead to premature labor or fetal abnormalities; methotrexate, which is a teratogen and immunogen; and systemic retinoids, which are also known teratogens, Dr. Kimball said. With respect to methotrexate in pregnancy, “the current recommendation extends to males, who should be advised to cease its use for 3 months prior to conception because of theoretical concern about chromosomal abnormalities,” she noted.

Regarding topical therapies, tazarotene, anthralin, calcipotriol, and coal tar should be avoided as well, said Dr. Kimball.

In all cases, putting a patient's risk into context is difficult given the limited and conflicting information that is available, Dr. Kimball said. “At the end of the day, you really have to guide women about the personal nature of these choices,” based on experience and the information that is available.

Dr. Kimball has served as a consultant and an investigator for Amgen Inc., Centocor Inc., Abbott Laboratories, NeoStrata Co., and Galderma; she is an investigator for Stiefel Laboratories Inc.; and has a fellowship funded by Centocor.