Diana Mahoney

STOWE, VT. — “Tell me you have a patient with a rash who also happens to have a seizure disorder [and it's] enough to make me stop what I'm doing and get right over,” Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The patient might have a drug hypersensitivity syndrome or toxic epidermal necrolysis—both of which have been associated with anticonvulsant therapy, Dr. Elston said in a presentation on life-threatening dermatoses at the conference. Time is critical for such patients, as prompt recognition and appropriate treatment often hold the key to survival, he stated.

Toxic epidermal necrolysis (TEN) is the most severe cutaneous manifestation associated with anticonvulsive therapy. The rare condition is most commonly associated with the aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin), but it has also been reported with other anticonvulsants, such as lamotrigine, particularly when used in combination with valproic acid, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

A diagnosis of anticonvulsant hypersensitivity disorder should be presumed if the rash is morbilliform or scarlatiniform and is accompanied by facial edema, fever, and/or lymphadenopathy. Additional clinical features often include hepatitis, eosinophilia, and atypical lymphocytosis.

Acute-onset rashes that present as severe mucosal erosions with epidermal detachment and widespread erythematosus macules may be either Stevens-Johnson syndrome (SJS) or TEN. The former, associated with a 5% mortality rate, is often defined by purpuric macules and atypical target lesions, full-thickness epidermal necrosis, mucous membrane involvement, and detachment of less than 10% of the total cutaneous surface.

Possibly a more severe variant of the same process, TEN shares the histologic features of SJS, but detachment affects more than 30% of the cutaneous surface and the mortality is significantly higher. Acute onset of intense skin tenderness also indicates TEN, Dr. Elston said.

Skin biopsy will show a combination of normal stratum corneum and keratinocyte necrosis, which is important for diagnosis because it rules out other serious dermatologic conditions.

A thorough patient history is also critical for accurate diagnosis and appropriate treatment, Dr. Elston emphasized, noting that delineating a drug exposure timeline is particularly important, as is determining previous exposure history. If the patient has been previously sensitized to the offending drugs, more rapid onset and a worse prognosis are likely, he noted.

The most important treatment is to withdraw the anticonvulsant immediately and switch to an alternative medication for seizure control. “Doing so requires extreme care because of the high degree of cross-reactivity” among the various agents—particularly, but not exclusively, the aromatic drugs, he noted.

“Lamotrigine [Lamictal] is not an aromatic, yet it has a black box warning about its association with SJS and TEN, especially when used in combination with valproic acid,” Dr. Elston said. “I also wouldn't use gabapentin because of the disturbing number of anecdotal reports associating it with recurrence of hypersensitivity reactions.”

Valproic acid has a low independent association with the skin eruptions, and “is probably the safest choice for alternative seizure control,” Dr. Elston noted.

Besides intravenous fluid replacement, the main types of symptomatic treatment for the more severe exfoliative conditions are the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances, Dr. Elston said. In fact, “patients should be transferred to a burn center if possible,” he noted. Burn center care can improve mortality, primarily because of the specialized and intensive nursing support, he said.

Patients should also be monitored by an ophthalmologist for ocular sequelae, and preventive measures should be taken.

In discussing drug therapy, Dr. Elston said he doesn't recommend systemic corticosteroids because in some studies they have been associated with increased mortality when used for more than 48 hours. Intravenous immunoglobulin is a promising but unproven therapy, he said. Thalidomide, proposed as a treatment for TEN because it is a potent inhibitor of tumor necrosis factor-α action, is not recommended. “A well-designed trial to study its effectiveness was stopped because of excess mortality” in patients receiving the drug, Dr. Elston said.

Although the causative mechanisms are not well established, drug hypersensitivity syndrome may be associated with reactivation of human herpes virus 6.

Prompt diagnosis, withdrawal of the causative drug, avoidance of cross-reactive drugs, and appropriate supportive care appear to be the best way to manage these patients, Dr. Elston said.

Toxic epidermal necrolysis resulted in full-thickness necrosis on this patient's trunk.

Follicular prominence, as on this patient's arm, can be caused by anticonvulsant hypersensitivity.

STOWE, VT. — “Tell me you have a patient with a rash who also happens to have a seizure disorder [and it's] enough to make me stop what I'm doing and get right over,” Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The patient might have a drug hypersensitivity syndrome or toxic epidermal necrolysis—both of which have been associated with anticonvulsant therapy, Dr. Elston said in a presentation on life-threatening dermatoses at the conference. Time is critical for such patients, as prompt recognition and appropriate treatment often hold the key to survival, he stated.

Toxic epidermal necrolysis (TEN) is the most severe cutaneous manifestation associated with anticonvulsive therapy. The rare condition is most commonly associated with the aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin), but it has also been reported with other anticonvulsants, such as lamotrigine, particularly when used in combination with valproic acid, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

A diagnosis of anticonvulsant hypersensitivity disorder should be presumed if the rash is morbilliform or scarlatiniform and is accompanied by facial edema, fever, and/or lymphadenopathy. Additional clinical features often include hepatitis, eosinophilia, and atypical lymphocytosis.

Acute-onset rashes that present as severe mucosal erosions with epidermal detachment and widespread erythematosus macules may be either Stevens-Johnson syndrome (SJS) or TEN. The former, associated with a 5% mortality rate, is often defined by purpuric macules and atypical target lesions, full-thickness epidermal necrosis, mucous membrane involvement, and detachment of less than 10% of the total cutaneous surface.

Possibly a more severe variant of the same process, TEN shares the histologic features of SJS, but detachment affects more than 30% of the cutaneous surface and the mortality is significantly higher. Acute onset of intense skin tenderness also indicates TEN, Dr. Elston said.

Skin biopsy will show a combination of normal stratum corneum and keratinocyte necrosis, which is important for diagnosis because it rules out other serious dermatologic conditions.

A thorough patient history is also critical for accurate diagnosis and appropriate treatment, Dr. Elston emphasized, noting that delineating a drug exposure timeline is particularly important, as is determining previous exposure history. If the patient has been previously sensitized to the offending drugs, more rapid onset and a worse prognosis are likely, he noted.

The most important treatment is to withdraw the anticonvulsant immediately and switch to an alternative medication for seizure control. “Doing so requires extreme care because of the high degree of cross-reactivity” among the various agents—particularly, but not exclusively, the aromatic drugs, he noted.

“Lamotrigine [Lamictal] is not an aromatic, yet it has a black box warning about its association with SJS and TEN, especially when used in combination with valproic acid,” Dr. Elston said. “I also wouldn't use gabapentin because of the disturbing number of anecdotal reports associating it with recurrence of hypersensitivity reactions.”

Valproic acid has a low independent association with the skin eruptions, and “is probably the safest choice for alternative seizure control,” Dr. Elston noted.

Besides intravenous fluid replacement, the main types of symptomatic treatment for the more severe exfoliative conditions are the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances, Dr. Elston said. In fact, “patients should be transferred to a burn center if possible,” he noted. Burn center care can improve mortality, primarily because of the specialized and intensive nursing support, he said.

Patients should also be monitored by an ophthalmologist for ocular sequelae, and preventive measures should be taken.

In discussing drug therapy, Dr. Elston said he doesn't recommend systemic corticosteroids because in some studies they have been associated with increased mortality when used for more than 48 hours. Intravenous immunoglobulin is a promising but unproven therapy, he said. Thalidomide, proposed as a treatment for TEN because it is a potent inhibitor of tumor necrosis factor-α action, is not recommended. “A well-designed trial to study its effectiveness was stopped because of excess mortality” in patients receiving the drug, Dr. Elston said.

Although the causative mechanisms are not well established, drug hypersensitivity syndrome may be associated with reactivation of human herpes virus 6.

Prompt diagnosis, withdrawal of the causative drug, avoidance of cross-reactive drugs, and appropriate supportive care appear to be the best way to manage these patients, Dr. Elston said.

Toxic epidermal necrolysis resulted in full-thickness necrosis on this patient's trunk.

Follicular prominence, as on this patient's arm, can be caused by anticonvulsant hypersensitivity.

STOWE, VT. — “Tell me you have a patient with a rash who also happens to have a seizure disorder [and it's] enough to make me stop what I'm doing and get right over,” Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The patient might have a drug hypersensitivity syndrome or toxic epidermal necrolysis—both of which have been associated with anticonvulsant therapy, Dr. Elston said in a presentation on life-threatening dermatoses at the conference. Time is critical for such patients, as prompt recognition and appropriate treatment often hold the key to survival, he stated.

Toxic epidermal necrolysis (TEN) is the most severe cutaneous manifestation associated with anticonvulsive therapy. The rare condition is most commonly associated with the aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin), but it has also been reported with other anticonvulsants, such as lamotrigine, particularly when used in combination with valproic acid, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

A diagnosis of anticonvulsant hypersensitivity disorder should be presumed if the rash is morbilliform or scarlatiniform and is accompanied by facial edema, fever, and/or lymphadenopathy. Additional clinical features often include hepatitis, eosinophilia, and atypical lymphocytosis.

Acute-onset rashes that present as severe mucosal erosions with epidermal detachment and widespread erythematosus macules may be either Stevens-Johnson syndrome (SJS) or TEN. The former, associated with a 5% mortality rate, is often defined by purpuric macules and atypical target lesions, full-thickness epidermal necrosis, mucous membrane involvement, and detachment of less than 10% of the total cutaneous surface.

Possibly a more severe variant of the same process, TEN shares the histologic features of SJS, but detachment affects more than 30% of the cutaneous surface and the mortality is significantly higher. Acute onset of intense skin tenderness also indicates TEN, Dr. Elston said.

Skin biopsy will show a combination of normal stratum corneum and keratinocyte necrosis, which is important for diagnosis because it rules out other serious dermatologic conditions.

A thorough patient history is also critical for accurate diagnosis and appropriate treatment, Dr. Elston emphasized, noting that delineating a drug exposure timeline is particularly important, as is determining previous exposure history. If the patient has been previously sensitized to the offending drugs, more rapid onset and a worse prognosis are likely, he noted.

The most important treatment is to withdraw the anticonvulsant immediately and switch to an alternative medication for seizure control. “Doing so requires extreme care because of the high degree of cross-reactivity” among the various agents—particularly, but not exclusively, the aromatic drugs, he noted.

“Lamotrigine [Lamictal] is not an aromatic, yet it has a black box warning about its association with SJS and TEN, especially when used in combination with valproic acid,” Dr. Elston said. “I also wouldn't use gabapentin because of the disturbing number of anecdotal reports associating it with recurrence of hypersensitivity reactions.”

Valproic acid has a low independent association with the skin eruptions, and “is probably the safest choice for alternative seizure control,” Dr. Elston noted.

Besides intravenous fluid replacement, the main types of symptomatic treatment for the more severe exfoliative conditions are the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances, Dr. Elston said. In fact, “patients should be transferred to a burn center if possible,” he noted. Burn center care can improve mortality, primarily because of the specialized and intensive nursing support, he said.

Patients should also be monitored by an ophthalmologist for ocular sequelae, and preventive measures should be taken.

In discussing drug therapy, Dr. Elston said he doesn't recommend systemic corticosteroids because in some studies they have been associated with increased mortality when used for more than 48 hours. Intravenous immunoglobulin is a promising but unproven therapy, he said. Thalidomide, proposed as a treatment for TEN because it is a potent inhibitor of tumor necrosis factor-α action, is not recommended. “A well-designed trial to study its effectiveness was stopped because of excess mortality” in patients receiving the drug, Dr. Elston said.

Although the causative mechanisms are not well established, drug hypersensitivity syndrome may be associated with reactivation of human herpes virus 6.

Prompt diagnosis, withdrawal of the causative drug, avoidance of cross-reactive drugs, and appropriate supportive care appear to be the best way to manage these patients, Dr. Elston said.

Toxic epidermal necrolysis resulted in full-thickness necrosis on this patient's trunk.

Follicular prominence, as on this patient's arm, can be caused by anticonvulsant hypersensitivity.

CAMBRIDGE, MASS. – A broad differential diagnosis and careful drug selection are essential to successfully treating bipolar illness in geriatric patients, M. Cornelia Cremens, M.D., said at a meeting on bipolar disorder sponsored by Harvard Medical School.

But the dearth of evidence-based guidelines for managing older bipolar patients makes both objectives difficult to attain, the geriatric psychiatrist said.

“Bipolar patients represent approximately 5%-20% of patients who require acute treatment in geriatric psychiatry, but depression and mania can be secondary to many other psychiatric or medical illnesses,” said Dr. Cremens of Massachusetts General Hospital, Boston.

“Psychotic symptoms are frequently associated with dementias of all types–delirium, depression, schizophrenia, and certain medical illnesses, such as Parkinson's disease,” she said. In addition, symptoms of depression can be side effects of prescribed medications.

With respect to treatment, pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” said Dr. Cremens. “Pharmacokinetic changes in elderly can increase the time to reach steady state concentrations and possibly prolong clearance.”

Hepatic function, renal clearance, and absorption may also be reduced in elderly patients, and increased distribution resulting from a higher fat-to-lean body mass ratio contributes to higher concentration of drug-to-dose ratio, she said. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder is made, treatment selection and dosing should be guided by the tolerability of specific agents. Treatment should not be initiated until a thorough medication/disease history has been taken and the results of baseline clinical and laboratory studies, neurologic examinations, and cognitive assessments have been evaluated.

In the absence of contraindications, lithium is one treatment of choice for bipolar disease in older patients. “Lithium has been prescribed extensively in this population, and many patients have tolerated prolonged use of it; however, the risk of toxicity is greater with the addition of medications … such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens said.

When prescribing lithium to elderly patients, initially target moderate concentration ranges, and gradually increase the dose. Be cognizant of conditions and treatments that might increase the concentration-to-dose ratio. In patients with comorbid brain disease, lithium dosing should be especially conservative, and patients should be watched for worsening of cognitive status, coarse tremor, and hypothyroidism.

In manic elderly patients, the anticonvulsant divalproex sodium can often be used as a first-line mood stabilizer. It's a reasonable alternative for patients who experience cognitive deterioration during lithium treatment. As with lithium, dosing should be conservative and gradually increased. Possible side effects include sedation and gait disturbance, as well as thrombocytopenia. The anticonvulsant carbamazepine is frequently used as second-line therapy for mania, but it carries a greater risk of hematologic toxicity than divalproex sodium, she said.

When initial mood stabilizing treatment is insufficient, adjunctive use of atypical antipsychotic medications has “been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” said Dr. Cremens.

The latter consideration is important, because elderly patients diagnosed with bipolar illness are more often depressed than manic. In fact, “bipolar depression in elderly may have been misdiagnosed for many years as unipolar depression, because manic states may not be recognized,” she said.

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population, Dr. Cremens said.

Because there are no evidence-based guidelines for treatment duration in this population, maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely “unless a contraindication arises due to a medical or neurological problem,” Dr. Cremens said.

CAMBRIDGE, MASS. – A broad differential diagnosis and careful drug selection are essential to successfully treating bipolar illness in geriatric patients, M. Cornelia Cremens, M.D., said at a meeting on bipolar disorder sponsored by Harvard Medical School.

But the dearth of evidence-based guidelines for managing older bipolar patients makes both objectives difficult to attain, the geriatric psychiatrist said.

“Bipolar patients represent approximately 5%-20% of patients who require acute treatment in geriatric psychiatry, but depression and mania can be secondary to many other psychiatric or medical illnesses,” said Dr. Cremens of Massachusetts General Hospital, Boston.

“Psychotic symptoms are frequently associated with dementias of all types–delirium, depression, schizophrenia, and certain medical illnesses, such as Parkinson's disease,” she said. In addition, symptoms of depression can be side effects of prescribed medications.

With respect to treatment, pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” said Dr. Cremens. “Pharmacokinetic changes in elderly can increase the time to reach steady state concentrations and possibly prolong clearance.”

Hepatic function, renal clearance, and absorption may also be reduced in elderly patients, and increased distribution resulting from a higher fat-to-lean body mass ratio contributes to higher concentration of drug-to-dose ratio, she said. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder is made, treatment selection and dosing should be guided by the tolerability of specific agents. Treatment should not be initiated until a thorough medication/disease history has been taken and the results of baseline clinical and laboratory studies, neurologic examinations, and cognitive assessments have been evaluated.

In the absence of contraindications, lithium is one treatment of choice for bipolar disease in older patients. “Lithium has been prescribed extensively in this population, and many patients have tolerated prolonged use of it; however, the risk of toxicity is greater with the addition of medications … such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens said.

When prescribing lithium to elderly patients, initially target moderate concentration ranges, and gradually increase the dose. Be cognizant of conditions and treatments that might increase the concentration-to-dose ratio. In patients with comorbid brain disease, lithium dosing should be especially conservative, and patients should be watched for worsening of cognitive status, coarse tremor, and hypothyroidism.

In manic elderly patients, the anticonvulsant divalproex sodium can often be used as a first-line mood stabilizer. It's a reasonable alternative for patients who experience cognitive deterioration during lithium treatment. As with lithium, dosing should be conservative and gradually increased. Possible side effects include sedation and gait disturbance, as well as thrombocytopenia. The anticonvulsant carbamazepine is frequently used as second-line therapy for mania, but it carries a greater risk of hematologic toxicity than divalproex sodium, she said.

When initial mood stabilizing treatment is insufficient, adjunctive use of atypical antipsychotic medications has “been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” said Dr. Cremens.

The latter consideration is important, because elderly patients diagnosed with bipolar illness are more often depressed than manic. In fact, “bipolar depression in elderly may have been misdiagnosed for many years as unipolar depression, because manic states may not be recognized,” she said.

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population, Dr. Cremens said.

Because there are no evidence-based guidelines for treatment duration in this population, maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely “unless a contraindication arises due to a medical or neurological problem,” Dr. Cremens said.

CAMBRIDGE, MASS. – A broad differential diagnosis and careful drug selection are essential to successfully treating bipolar illness in geriatric patients, M. Cornelia Cremens, M.D., said at a meeting on bipolar disorder sponsored by Harvard Medical School.

But the dearth of evidence-based guidelines for managing older bipolar patients makes both objectives difficult to attain, the geriatric psychiatrist said.

“Bipolar patients represent approximately 5%-20% of patients who require acute treatment in geriatric psychiatry, but depression and mania can be secondary to many other psychiatric or medical illnesses,” said Dr. Cremens of Massachusetts General Hospital, Boston.

“Psychotic symptoms are frequently associated with dementias of all types–delirium, depression, schizophrenia, and certain medical illnesses, such as Parkinson's disease,” she said. In addition, symptoms of depression can be side effects of prescribed medications.

With respect to treatment, pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” said Dr. Cremens. “Pharmacokinetic changes in elderly can increase the time to reach steady state concentrations and possibly prolong clearance.”

Hepatic function, renal clearance, and absorption may also be reduced in elderly patients, and increased distribution resulting from a higher fat-to-lean body mass ratio contributes to higher concentration of drug-to-dose ratio, she said. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder is made, treatment selection and dosing should be guided by the tolerability of specific agents. Treatment should not be initiated until a thorough medication/disease history has been taken and the results of baseline clinical and laboratory studies, neurologic examinations, and cognitive assessments have been evaluated.

In the absence of contraindications, lithium is one treatment of choice for bipolar disease in older patients. “Lithium has been prescribed extensively in this population, and many patients have tolerated prolonged use of it; however, the risk of toxicity is greater with the addition of medications … such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens said.

When prescribing lithium to elderly patients, initially target moderate concentration ranges, and gradually increase the dose. Be cognizant of conditions and treatments that might increase the concentration-to-dose ratio. In patients with comorbid brain disease, lithium dosing should be especially conservative, and patients should be watched for worsening of cognitive status, coarse tremor, and hypothyroidism.

In manic elderly patients, the anticonvulsant divalproex sodium can often be used as a first-line mood stabilizer. It's a reasonable alternative for patients who experience cognitive deterioration during lithium treatment. As with lithium, dosing should be conservative and gradually increased. Possible side effects include sedation and gait disturbance, as well as thrombocytopenia. The anticonvulsant carbamazepine is frequently used as second-line therapy for mania, but it carries a greater risk of hematologic toxicity than divalproex sodium, she said.

When initial mood stabilizing treatment is insufficient, adjunctive use of atypical antipsychotic medications has “been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” said Dr. Cremens.

The latter consideration is important, because elderly patients diagnosed with bipolar illness are more often depressed than manic. In fact, “bipolar depression in elderly may have been misdiagnosed for many years as unipolar depression, because manic states may not be recognized,” she said.

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population, Dr. Cremens said.

Because there are no evidence-based guidelines for treatment duration in this population, maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely “unless a contraindication arises due to a medical or neurological problem,” Dr. Cremens said.

HARROGATE, ENGLAND — A single bone mineral density measurement early in menopause is a strong predictor of future bone status in women not considered at risk for osteoporosis, a study has shown.

Despite various rates of bone mineral loss among individuals and measurement sites, baseline bone mineral density (BMD) measures of 766 women in the Danish Osteoporosis Prevention Study predicted 75% of the variation in lumbar spine BMD and 74% of femoral neck BMD variation over 10 years, Bo Abrahamsen, M.D., reported at the annual conference of the National Osteoporosis Society.

None of the women were taking hormone therapy or antiresorptive drugs. The baseline scans were acquired within 2 years of menopause.

Baseline lumbar spine T-scores greater than −1.2 were associated with a 90% negative predictive value for developing osteoporosis over 10 years, whereas a lumbar spine T-score greater than 0.5 had a negative predictive value of 100%.

A baseline femoral neck T-score greater than −1.7 had a 90% negative predictive value for femoral neck osteoporosis.

“No women developed femoral neck osteoporosis in the absence of baseline femoral neck osteopenia,” said Dr. Abrahamsen of Odense (Denmark) University Hospital.

At baseline, having a lumbar spine T-score greater than −1.0 or a femoral neck T-score greater than −0.5 was associated with a 90% negative predictive value for osteoporosis of the lumbar spine and/or the femoral neck.

“Women with lumbar spine osteopenia at baseline had a 46% risk for developing osteoporosis of the femoral neck or lumbar spine,” Dr. Abrahamsen explained.

At the same time, fewer than 10% of women whose T-scores of the spine or femoral neck dipped below −2.5 within 10 years had spinal osteopenia at their initial visit, he said.

The findings support the role of bone density measurements in the first years after menopause.

“There is an increasing demand for [bone density measurement] with the onset of menopause due to concerns about the safety of hormone replacement therapy and a possible need for considering other treatment,” he said. “We know that, despite the fact that the average rate of bone mineral loss is only a few percent per year, there is much individual variation in those rates. These results tell us that much of the variation in future bone mineral density can be predicted by baseline BMD.”

As such, baseline measures should be considered for long-term treatment planning, he concluded.

HARROGATE, ENGLAND — A single bone mineral density measurement early in menopause is a strong predictor of future bone status in women not considered at risk for osteoporosis, a study has shown.

Despite various rates of bone mineral loss among individuals and measurement sites, baseline bone mineral density (BMD) measures of 766 women in the Danish Osteoporosis Prevention Study predicted 75% of the variation in lumbar spine BMD and 74% of femoral neck BMD variation over 10 years, Bo Abrahamsen, M.D., reported at the annual conference of the National Osteoporosis Society.

None of the women were taking hormone therapy or antiresorptive drugs. The baseline scans were acquired within 2 years of menopause.

Baseline lumbar spine T-scores greater than −1.2 were associated with a 90% negative predictive value for developing osteoporosis over 10 years, whereas a lumbar spine T-score greater than 0.5 had a negative predictive value of 100%.

A baseline femoral neck T-score greater than −1.7 had a 90% negative predictive value for femoral neck osteoporosis.

“No women developed femoral neck osteoporosis in the absence of baseline femoral neck osteopenia,” said Dr. Abrahamsen of Odense (Denmark) University Hospital.

At baseline, having a lumbar spine T-score greater than −1.0 or a femoral neck T-score greater than −0.5 was associated with a 90% negative predictive value for osteoporosis of the lumbar spine and/or the femoral neck.

“Women with lumbar spine osteopenia at baseline had a 46% risk for developing osteoporosis of the femoral neck or lumbar spine,” Dr. Abrahamsen explained.

At the same time, fewer than 10% of women whose T-scores of the spine or femoral neck dipped below −2.5 within 10 years had spinal osteopenia at their initial visit, he said.

The findings support the role of bone density measurements in the first years after menopause.

“There is an increasing demand for [bone density measurement] with the onset of menopause due to concerns about the safety of hormone replacement therapy and a possible need for considering other treatment,” he said. “We know that, despite the fact that the average rate of bone mineral loss is only a few percent per year, there is much individual variation in those rates. These results tell us that much of the variation in future bone mineral density can be predicted by baseline BMD.”

As such, baseline measures should be considered for long-term treatment planning, he concluded.

HARROGATE, ENGLAND — A single bone mineral density measurement early in menopause is a strong predictor of future bone status in women not considered at risk for osteoporosis, a study has shown.

Despite various rates of bone mineral loss among individuals and measurement sites, baseline bone mineral density (BMD) measures of 766 women in the Danish Osteoporosis Prevention Study predicted 75% of the variation in lumbar spine BMD and 74% of femoral neck BMD variation over 10 years, Bo Abrahamsen, M.D., reported at the annual conference of the National Osteoporosis Society.

None of the women were taking hormone therapy or antiresorptive drugs. The baseline scans were acquired within 2 years of menopause.

Baseline lumbar spine T-scores greater than −1.2 were associated with a 90% negative predictive value for developing osteoporosis over 10 years, whereas a lumbar spine T-score greater than 0.5 had a negative predictive value of 100%.

A baseline femoral neck T-score greater than −1.7 had a 90% negative predictive value for femoral neck osteoporosis.

“No women developed femoral neck osteoporosis in the absence of baseline femoral neck osteopenia,” said Dr. Abrahamsen of Odense (Denmark) University Hospital.

At baseline, having a lumbar spine T-score greater than −1.0 or a femoral neck T-score greater than −0.5 was associated with a 90% negative predictive value for osteoporosis of the lumbar spine and/or the femoral neck.

“Women with lumbar spine osteopenia at baseline had a 46% risk for developing osteoporosis of the femoral neck or lumbar spine,” Dr. Abrahamsen explained.

At the same time, fewer than 10% of women whose T-scores of the spine or femoral neck dipped below −2.5 within 10 years had spinal osteopenia at their initial visit, he said.

The findings support the role of bone density measurements in the first years after menopause.

“There is an increasing demand for [bone density measurement] with the onset of menopause due to concerns about the safety of hormone replacement therapy and a possible need for considering other treatment,” he said. “We know that, despite the fact that the average rate of bone mineral loss is only a few percent per year, there is much individual variation in those rates. These results tell us that much of the variation in future bone mineral density can be predicted by baseline BMD.”

As such, baseline measures should be considered for long-term treatment planning, he concluded.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m2, and amenorrhea as significant risk factors associated with a lower bone mineral density. Such findings, Dr. Koshy said suggest that “focused use of bone densitometry in women younger than 50 with any of these risk factors can help to identify patients with future fracture risk who may merit osteoporosis prevention.”

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

When it comes to drug therapy for migraines, don't treat children like little adults.

There are currently no agents approved by the FDA for the acute treatment of migraine in children or adolescents. New practice guidelines developed by the American Academy of Neurology (AAN) support the use of conventional analgesic medications, such as ibuprofen and acetaminophen, for acute migraine pain in children aged 6 years and older but do not recommend most of the newer drugs being used to prevent and treat adult migraine pain.

One exception is sumatriptan nasal spray (Imitrex), which the guidelines recommend for treating migraine pain in children older than 12 years.

“It is not that the newer medications are ineffective in children and adolescents,” said lead author Donald W. Lewis, M.D. “Rather, they have been insufficiently studied in the pediatric population.” In fact, the most definitive conclusion the guideline authors reached was that there is a “clear and urgent need for methodologically sound randomized controlled trials for the use of prophylactic drugs in pediatric migraine,” Dr. Lewis said in an interview with CLINICAL NEUROLOGY NEWS.

Dr. Lewis, a pediatric neurologist at Children's Hospital of the King's Daughters in Norfolk, Va., and his coauthors reviewed the results of 166 placebo-controlled trials of migraine therapy conducted in children between the ages of 3 and 18 years during the last 2 decades. The evaluation included 5 agents for acute migraine treatment and 12 for migraine prevention. The authors used a four-tiered classification system to assess the quality of the available evidence, to determine whether the evidence supported specific recommendations, and, if it did, to gauge the strength of the recommendations (Neurology 2004;63:2215-24).

The treatment agents included in the evaluation were ibuprofen, acetaminophen, sumatriptan nasal spray, rizatriptan (Maxalt), and zolmitriptan (Zomig). The preventive agents were flunarizine (Sibelium), cyproheptadine (Periactin), amitriptyline (Elavil), divalproex sodium (Depakote), topiramate (Topamax), levetiracetam (Keppra), propranolol (Inderal), trazodone (Desyrel), pizotifen (Sandomigran), nimodipine (Nimotop), and clonidine (Catapres).

Of drugs to treat acute migraine, both ibuprofen and sumatriptan nasal spray were classified as effective, although the data for nasal sumatriptan only support a recommendation for use in adolescents. Acetaminophen was judged probably effective and also recommended for use. Both the oral triptan preparations as well as subcutaneous sumatriptan were not recommended because there were no data to support or discourage their use.

Only one of the preventive drugs—flunarizine—has been studied in rigorous controlled trials in children and was deemed by the guideline authors as “probably effective” in children. However, the calcium channel blocker is not available in the United States.

Of the remaining prophylactic agents, there is insufficient evidence to recommend cyproheptadine, amitriptyline, divalproex sodium, topiramate, or levetiracetam, according to the guidelines. Propranolol and trazodone are not recommended because of conflicting evidence, and pizotifen, nimodipine, and clonidine are not recommended because the data did not show them to be effective.

Given the prevalence of migraine headaches in children—up to 23% in 11- to 15-year-olds—“there is a disappointing lack of evidence to support pharmacologic interventions,” said Dr. Lewis. Although the failure of the various therapeutic and prophylactic drugs to demonstrate statistically significant efficacy does not preclude their use in the pediatric population, “good clinical judgment has to be used, particularly with respect to dosing and age ranges,” he said.

Fortunately, some proven adult interventions are effective, and the guidelines recommend their use in children as well.

“Not all children require drug treatment for migraines, and in fact it is often not the first line of attack and should never be the sole approach,” said Dr. Lewis. Lifestyle changes are often in order and can be very effective, he said. “In teens especially, poor diet, lack of sleep, too much caffeine, and school and social stress is a big problem. The first step is to modify these factors.”

Lifestyle information, including nutritional education, a prescription for daily exercise, and, when indicated, behavioral therapy, should be part of every migraine treatment protocol, as should a migraine calendar to record the frequency and intensity of migraine.

These steps help to ensure that each child gets the treatment that meets his or her individual needs.

“There is no one 'right' way to treat migraine in children,” Dr. Lewis said. “Interventions need to be tailored to the individual.”

One often overlooked key to the development of successful interventions, Dr. Lewis contended, is the fact that parents, teachers, caregivers, and physicians often don't recognize migraines in children—either because of a misperception that children don't experience migraines or because the children are not able to fully articulate the nature of the pain.

“The problem needs to be fully recognized, and potential interventions need to be more rigorously pursued” before more definitive treatment recommendations can be made, he said.

In addition to their call for well designed, multicenter clinical trials of migraine interventions in children and adolescents, the guideline authors also highlight the need for standardized criteria for diagnosing migraine headaches and for classifying treatment response in this population.

Further, future research trials should result in increased understanding of observed variations in effects of treatments by age and sex, according to Dr. Lewis.

Both the American Academy of Pediatrics and the American Headache Society have endorsed the new guidelines, according to a press release issued by the American Academy of Neurology.

When it comes to drug therapy for migraines, don't treat children like little adults.

There are currently no agents approved by the FDA for the acute treatment of migraine in children or adolescents. New practice guidelines developed by the American Academy of Neurology (AAN) support the use of conventional analgesic medications, such as ibuprofen and acetaminophen, for acute migraine pain in children aged 6 years and older but do not recommend most of the newer drugs being used to prevent and treat adult migraine pain.

One exception is sumatriptan nasal spray (Imitrex), which the guidelines recommend for treating migraine pain in children older than 12 years.

“It is not that the newer medications are ineffective in children and adolescents,” said lead author Donald W. Lewis, M.D. “Rather, they have been insufficiently studied in the pediatric population.” In fact, the most definitive conclusion the guideline authors reached was that there is a “clear and urgent need for methodologically sound randomized controlled trials for the use of prophylactic drugs in pediatric migraine,” Dr. Lewis said in an interview with CLINICAL NEUROLOGY NEWS.

Dr. Lewis, a pediatric neurologist at Children's Hospital of the King's Daughters in Norfolk, Va., and his coauthors reviewed the results of 166 placebo-controlled trials of migraine therapy conducted in children between the ages of 3 and 18 years during the last 2 decades. The evaluation included 5 agents for acute migraine treatment and 12 for migraine prevention. The authors used a four-tiered classification system to assess the quality of the available evidence, to determine whether the evidence supported specific recommendations, and, if it did, to gauge the strength of the recommendations (Neurology 2004;63:2215-24).

The treatment agents included in the evaluation were ibuprofen, acetaminophen, sumatriptan nasal spray, rizatriptan (Maxalt), and zolmitriptan (Zomig). The preventive agents were flunarizine (Sibelium), cyproheptadine (Periactin), amitriptyline (Elavil), divalproex sodium (Depakote), topiramate (Topamax), levetiracetam (Keppra), propranolol (Inderal), trazodone (Desyrel), pizotifen (Sandomigran), nimodipine (Nimotop), and clonidine (Catapres).

Of drugs to treat acute migraine, both ibuprofen and sumatriptan nasal spray were classified as effective, although the data for nasal sumatriptan only support a recommendation for use in adolescents. Acetaminophen was judged probably effective and also recommended for use. Both the oral triptan preparations as well as subcutaneous sumatriptan were not recommended because there were no data to support or discourage their use.

Only one of the preventive drugs—flunarizine—has been studied in rigorous controlled trials in children and was deemed by the guideline authors as “probably effective” in children. However, the calcium channel blocker is not available in the United States.

Of the remaining prophylactic agents, there is insufficient evidence to recommend cyproheptadine, amitriptyline, divalproex sodium, topiramate, or levetiracetam, according to the guidelines. Propranolol and trazodone are not recommended because of conflicting evidence, and pizotifen, nimodipine, and clonidine are not recommended because the data did not show them to be effective.

Given the prevalence of migraine headaches in children—up to 23% in 11- to 15-year-olds—“there is a disappointing lack of evidence to support pharmacologic interventions,” said Dr. Lewis. Although the failure of the various therapeutic and prophylactic drugs to demonstrate statistically significant efficacy does not preclude their use in the pediatric population, “good clinical judgment has to be used, particularly with respect to dosing and age ranges,” he said.

Fortunately, some proven adult interventions are effective, and the guidelines recommend their use in children as well.

“Not all children require drug treatment for migraines, and in fact it is often not the first line of attack and should never be the sole approach,” said Dr. Lewis. Lifestyle changes are often in order and can be very effective, he said. “In teens especially, poor diet, lack of sleep, too much caffeine, and school and social stress is a big problem. The first step is to modify these factors.”

Lifestyle information, including nutritional education, a prescription for daily exercise, and, when indicated, behavioral therapy, should be part of every migraine treatment protocol, as should a migraine calendar to record the frequency and intensity of migraine.

These steps help to ensure that each child gets the treatment that meets his or her individual needs.

“There is no one 'right' way to treat migraine in children,” Dr. Lewis said. “Interventions need to be tailored to the individual.”

One often overlooked key to the development of successful interventions, Dr. Lewis contended, is the fact that parents, teachers, caregivers, and physicians often don't recognize migraines in children—either because of a misperception that children don't experience migraines or because the children are not able to fully articulate the nature of the pain.

“The problem needs to be fully recognized, and potential interventions need to be more rigorously pursued” before more definitive treatment recommendations can be made, he said.

In addition to their call for well designed, multicenter clinical trials of migraine interventions in children and adolescents, the guideline authors also highlight the need for standardized criteria for diagnosing migraine headaches and for classifying treatment response in this population.

Further, future research trials should result in increased understanding of observed variations in effects of treatments by age and sex, according to Dr. Lewis.

Both the American Academy of Pediatrics and the American Headache Society have endorsed the new guidelines, according to a press release issued by the American Academy of Neurology.

When it comes to drug therapy for migraines, don't treat children like little adults.

There are currently no agents approved by the FDA for the acute treatment of migraine in children or adolescents. New practice guidelines developed by the American Academy of Neurology (AAN) support the use of conventional analgesic medications, such as ibuprofen and acetaminophen, for acute migraine pain in children aged 6 years and older but do not recommend most of the newer drugs being used to prevent and treat adult migraine pain.

One exception is sumatriptan nasal spray (Imitrex), which the guidelines recommend for treating migraine pain in children older than 12 years.

“It is not that the newer medications are ineffective in children and adolescents,” said lead author Donald W. Lewis, M.D. “Rather, they have been insufficiently studied in the pediatric population.” In fact, the most definitive conclusion the guideline authors reached was that there is a “clear and urgent need for methodologically sound randomized controlled trials for the use of prophylactic drugs in pediatric migraine,” Dr. Lewis said in an interview with CLINICAL NEUROLOGY NEWS.

Dr. Lewis, a pediatric neurologist at Children's Hospital of the King's Daughters in Norfolk, Va., and his coauthors reviewed the results of 166 placebo-controlled trials of migraine therapy conducted in children between the ages of 3 and 18 years during the last 2 decades. The evaluation included 5 agents for acute migraine treatment and 12 for migraine prevention. The authors used a four-tiered classification system to assess the quality of the available evidence, to determine whether the evidence supported specific recommendations, and, if it did, to gauge the strength of the recommendations (Neurology 2004;63:2215-24).

The treatment agents included in the evaluation were ibuprofen, acetaminophen, sumatriptan nasal spray, rizatriptan (Maxalt), and zolmitriptan (Zomig). The preventive agents were flunarizine (Sibelium), cyproheptadine (Periactin), amitriptyline (Elavil), divalproex sodium (Depakote), topiramate (Topamax), levetiracetam (Keppra), propranolol (Inderal), trazodone (Desyrel), pizotifen (Sandomigran), nimodipine (Nimotop), and clonidine (Catapres).

Of drugs to treat acute migraine, both ibuprofen and sumatriptan nasal spray were classified as effective, although the data for nasal sumatriptan only support a recommendation for use in adolescents. Acetaminophen was judged probably effective and also recommended for use. Both the oral triptan preparations as well as subcutaneous sumatriptan were not recommended because there were no data to support or discourage their use.

Only one of the preventive drugs—flunarizine—has been studied in rigorous controlled trials in children and was deemed by the guideline authors as “probably effective” in children. However, the calcium channel blocker is not available in the United States.

Of the remaining prophylactic agents, there is insufficient evidence to recommend cyproheptadine, amitriptyline, divalproex sodium, topiramate, or levetiracetam, according to the guidelines. Propranolol and trazodone are not recommended because of conflicting evidence, and pizotifen, nimodipine, and clonidine are not recommended because the data did not show them to be effective.

Given the prevalence of migraine headaches in children—up to 23% in 11- to 15-year-olds—“there is a disappointing lack of evidence to support pharmacologic interventions,” said Dr. Lewis. Although the failure of the various therapeutic and prophylactic drugs to demonstrate statistically significant efficacy does not preclude their use in the pediatric population, “good clinical judgment has to be used, particularly with respect to dosing and age ranges,” he said.

Fortunately, some proven adult interventions are effective, and the guidelines recommend their use in children as well.

“Not all children require drug treatment for migraines, and in fact it is often not the first line of attack and should never be the sole approach,” said Dr. Lewis. Lifestyle changes are often in order and can be very effective, he said. “In teens especially, poor diet, lack of sleep, too much caffeine, and school and social stress is a big problem. The first step is to modify these factors.”

Lifestyle information, including nutritional education, a prescription for daily exercise, and, when indicated, behavioral therapy, should be part of every migraine treatment protocol, as should a migraine calendar to record the frequency and intensity of migraine.

These steps help to ensure that each child gets the treatment that meets his or her individual needs.

“There is no one 'right' way to treat migraine in children,” Dr. Lewis said. “Interventions need to be tailored to the individual.”

One often overlooked key to the development of successful interventions, Dr. Lewis contended, is the fact that parents, teachers, caregivers, and physicians often don't recognize migraines in children—either because of a misperception that children don't experience migraines or because the children are not able to fully articulate the nature of the pain.

“The problem needs to be fully recognized, and potential interventions need to be more rigorously pursued” before more definitive treatment recommendations can be made, he said.

In addition to their call for well designed, multicenter clinical trials of migraine interventions in children and adolescents, the guideline authors also highlight the need for standardized criteria for diagnosing migraine headaches and for classifying treatment response in this population.

Further, future research trials should result in increased understanding of observed variations in effects of treatments by age and sex, according to Dr. Lewis.

Both the American Academy of Pediatrics and the American Headache Society have endorsed the new guidelines, according to a press release issued by the American Academy of Neurology.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

BOSTON — Persistent musculoskeletal pain, headache, fatigue, and cognitive dysfunction that occur for no apparent reason over a prolonged period of time are key elements of a clinical diagnosis of chronic Lyme disease in children, results of a retrospective study have shown.

“While there have been reports on the clinical manifestations of chronic Lyme disease in adults, there has not been a detailing of the clinical aspects of the condition in the pediatric population, making the diagnosis especially challenging,” said Sam T. Donta, M.D., in a presentation at the annual meeting of the Infectious Disease Society of America.

In an effort to identify the most telling clinical symptoms, the reliability of serologic studies, and the effects of drug therapy, Dr. Donta reviewed the clinical histories, serologies, and treatment results of 101 patients aged 2–19 years who were evaluated at Falmouth Hospital in Massachusetts for chronic Lyme disease. Tick bites occurred in 24% of the patients.

Musculoskeletal symptoms occurred in 90% of the patients, and fatigue, headache, and cognitive dysfunction were reported in 84%, 78%, and 74% of the patients, respectively. Other symptoms that occurred with some frequency included stomach pains or nausea (48%), paresthesias (46%), eye symptoms (40%), and fevers or sweats (39%), Dr. Donta noted. Typical and atypical rashes were reported in 15% and 25% of the patients, respectively.

About 79% of the patients had other symptoms, such as dizziness, palpitations, and tremors, said Dr. Donta, who has private practices in infectious disease in Boston and Falmouth.

Bell's palsy, which is often the first neurologic symptom of Lyme disease, was reported in five patients. Of the total study population, 29 patients had undergone a brain SPECT (single photon emission computed tomography) scan, eight of which showed some changes in blood flow to various parts of the brain. Such changes, primarily to the temporal and frontal lobes, are present in about 75% of patients with chronic Lyme disease, Dr. Donta stated.

Western blot serologic testing showed one or more reactions by IgM in 74% of the patients and by IgG in 82%. Enzyme immunoassay titers were positive in 65% of the patients tested. “Clearly, serologic studies can be helpful in supporting the clinical diagnosis,” said Dr. Donta, but they are not definitive on their own.

All of the patients in the cohort were treated with tetracycline or a combination of a macrolide antibiotic with hydroxychloroquine over a 4- to 8-month period, and 75% of them were cured or sustained clinical improvement, Dr. Donta noted.

The key is making sure the appropriate antibiotic is used and that therapy is adhered to and sustained for a long enough period, he said. Also, “the earlier in the disease process treatment begins, the more successful it will be.”

BOSTON — Persistent musculoskeletal pain, headache, fatigue, and cognitive dysfunction that occur for no apparent reason over a prolonged period of time are key elements of a clinical diagnosis of chronic Lyme disease in children, results of a retrospective study have shown.

“While there have been reports on the clinical manifestations of chronic Lyme disease in adults, there has not been a detailing of the clinical aspects of the condition in the pediatric population, making the diagnosis especially challenging,” said Sam T. Donta, M.D., in a presentation at the annual meeting of the Infectious Disease Society of America.

In an effort to identify the most telling clinical symptoms, the reliability of serologic studies, and the effects of drug therapy, Dr. Donta reviewed the clinical histories, serologies, and treatment results of 101 patients aged 2–19 years who were evaluated at Falmouth Hospital in Massachusetts for chronic Lyme disease. Tick bites occurred in 24% of the patients.

Musculoskeletal symptoms occurred in 90% of the patients, and fatigue, headache, and cognitive dysfunction were reported in 84%, 78%, and 74% of the patients, respectively. Other symptoms that occurred with some frequency included stomach pains or nausea (48%), paresthesias (46%), eye symptoms (40%), and fevers or sweats (39%), Dr. Donta noted. Typical and atypical rashes were reported in 15% and 25% of the patients, respectively.

About 79% of the patients had other symptoms, such as dizziness, palpitations, and tremors, said Dr. Donta, who has private practices in infectious disease in Boston and Falmouth.

Bell's palsy, which is often the first neurologic symptom of Lyme disease, was reported in five patients. Of the total study population, 29 patients had undergone a brain SPECT (single photon emission computed tomography) scan, eight of which showed some changes in blood flow to various parts of the brain. Such changes, primarily to the temporal and frontal lobes, are present in about 75% of patients with chronic Lyme disease, Dr. Donta stated.

Western blot serologic testing showed one or more reactions by IgM in 74% of the patients and by IgG in 82%. Enzyme immunoassay titers were positive in 65% of the patients tested. “Clearly, serologic studies can be helpful in supporting the clinical diagnosis,” said Dr. Donta, but they are not definitive on their own.

All of the patients in the cohort were treated with tetracycline or a combination of a macrolide antibiotic with hydroxychloroquine over a 4- to 8-month period, and 75% of them were cured or sustained clinical improvement, Dr. Donta noted.

The key is making sure the appropriate antibiotic is used and that therapy is adhered to and sustained for a long enough period, he said. Also, “the earlier in the disease process treatment begins, the more successful it will be.”

BOSTON — Persistent musculoskeletal pain, headache, fatigue, and cognitive dysfunction that occur for no apparent reason over a prolonged period of time are key elements of a clinical diagnosis of chronic Lyme disease in children, results of a retrospective study have shown.

“While there have been reports on the clinical manifestations of chronic Lyme disease in adults, there has not been a detailing of the clinical aspects of the condition in the pediatric population, making the diagnosis especially challenging,” said Sam T. Donta, M.D., in a presentation at the annual meeting of the Infectious Disease Society of America.

In an effort to identify the most telling clinical symptoms, the reliability of serologic studies, and the effects of drug therapy, Dr. Donta reviewed the clinical histories, serologies, and treatment results of 101 patients aged 2–19 years who were evaluated at Falmouth Hospital in Massachusetts for chronic Lyme disease. Tick bites occurred in 24% of the patients.

Musculoskeletal symptoms occurred in 90% of the patients, and fatigue, headache, and cognitive dysfunction were reported in 84%, 78%, and 74% of the patients, respectively. Other symptoms that occurred with some frequency included stomach pains or nausea (48%), paresthesias (46%), eye symptoms (40%), and fevers or sweats (39%), Dr. Donta noted. Typical and atypical rashes were reported in 15% and 25% of the patients, respectively.

About 79% of the patients had other symptoms, such as dizziness, palpitations, and tremors, said Dr. Donta, who has private practices in infectious disease in Boston and Falmouth.

Bell's palsy, which is often the first neurologic symptom of Lyme disease, was reported in five patients. Of the total study population, 29 patients had undergone a brain SPECT (single photon emission computed tomography) scan, eight of which showed some changes in blood flow to various parts of the brain. Such changes, primarily to the temporal and frontal lobes, are present in about 75% of patients with chronic Lyme disease, Dr. Donta stated.

Western blot serologic testing showed one or more reactions by IgM in 74% of the patients and by IgG in 82%. Enzyme immunoassay titers were positive in 65% of the patients tested. “Clearly, serologic studies can be helpful in supporting the clinical diagnosis,” said Dr. Donta, but they are not definitive on their own.

All of the patients in the cohort were treated with tetracycline or a combination of a macrolide antibiotic with hydroxychloroquine over a 4- to 8-month period, and 75% of them were cured or sustained clinical improvement, Dr. Donta noted.

The key is making sure the appropriate antibiotic is used and that therapy is adhered to and sustained for a long enough period, he said. Also, “the earlier in the disease process treatment begins, the more successful it will be.”

CHICAGO — Electronic medical records can provide the foundation for an effective “virtual” medical home for families and youth who seek health care in homeless and domestic violence shelters, a pilot program has demonstrated.

As part of a 5-year Anne E. Dyson Community Pediatrics Training Initiative grant, Indiana University and Wishard Health Services of Indianapolis have established an electronic connection (via the Regenstrief Medical Records System) between the community health service network's computer systems and the Julian Center for Domestic Violence shelter for battered women and children in Indianapolis. The shelter provides services to nearly 1,000 women and children annually.

The computer system links all of the large hospitals of Indianapolis, 13 homeless care sites, 44 clinics/offices in the community, and state health departments. When parents and children seek care at the domestic violence shelter, health care providers can access medical information for these patients in a password-protected format and can document the services provided.

This system “essentially facilitates a virtual medical home until a permanent medical home is established,” Dianna L. Fox, M.D., of Indiana University reported in a poster presentation at a conference on the Community Access to Child Health and Medical Home.

“Through an accessible computerized documentation system, providers can effectively transition youth in need to a permanent medical home,” Dr. Fox said.

CHICAGO — Electronic medical records can provide the foundation for an effective “virtual” medical home for families and youth who seek health care in homeless and domestic violence shelters, a pilot program has demonstrated.

As part of a 5-year Anne E. Dyson Community Pediatrics Training Initiative grant, Indiana University and Wishard Health Services of Indianapolis have established an electronic connection (via the Regenstrief Medical Records System) between the community health service network's computer systems and the Julian Center for Domestic Violence shelter for battered women and children in Indianapolis. The shelter provides services to nearly 1,000 women and children annually.

The computer system links all of the large hospitals of Indianapolis, 13 homeless care sites, 44 clinics/offices in the community, and state health departments. When parents and children seek care at the domestic violence shelter, health care providers can access medical information for these patients in a password-protected format and can document the services provided.

This system “essentially facilitates a virtual medical home until a permanent medical home is established,” Dianna L. Fox, M.D., of Indiana University reported in a poster presentation at a conference on the Community Access to Child Health and Medical Home.

“Through an accessible computerized documentation system, providers can effectively transition youth in need to a permanent medical home,” Dr. Fox said.

CHICAGO — Electronic medical records can provide the foundation for an effective “virtual” medical home for families and youth who seek health care in homeless and domestic violence shelters, a pilot program has demonstrated.

As part of a 5-year Anne E. Dyson Community Pediatrics Training Initiative grant, Indiana University and Wishard Health Services of Indianapolis have established an electronic connection (via the Regenstrief Medical Records System) between the community health service network's computer systems and the Julian Center for Domestic Violence shelter for battered women and children in Indianapolis. The shelter provides services to nearly 1,000 women and children annually.

The computer system links all of the large hospitals of Indianapolis, 13 homeless care sites, 44 clinics/offices in the community, and state health departments. When parents and children seek care at the domestic violence shelter, health care providers can access medical information for these patients in a password-protected format and can document the services provided.

This system “essentially facilitates a virtual medical home until a permanent medical home is established,” Dianna L. Fox, M.D., of Indiana University reported in a poster presentation at a conference on the Community Access to Child Health and Medical Home.

“Through an accessible computerized documentation system, providers can effectively transition youth in need to a permanent medical home,” Dr. Fox said.

BOSTON — Many physicians do not follow recommended guidelines for the diagnosis and management of children with pharyngitis, according to the results of a Centers for Disease Control and Prevention survey.

Although pharyngitis is one of the most common reasons for prescribing antibiotics, only 15%–30% of pediatric episodes are caused by group A streptococci and helped by antibiotics, CDC epidemiologist Sarah Y. Park, M.D., said in a presentation at the annual meeting of the Infectious Diseases Society of America.

Numerous studies have demonstrated that it is not possible on clinical grounds to differentiate streptococcal from viral pharyngitis, yet 278 of 505 eligible pediatricians and family medicine physicians (55%) who completed the CDC survey said they did not wait for laboratory confirmation of bacterial pharyngitis before initiating antibiotic therapy.

In addition, 64 of the respondents (13%) said they prescribed antibiotics based on clinical findings alone.

Diagnostic recommendations for pharyngitis are throat culture alone or a rapid antigen-detection test with throat culture backup, in conjunction with clinical and epidemiologic findings, said Dr. Park. “Diagnosis based on clinical findings alone is not recommended.

Most physicians tend to overestimate the probability of a streptococcal infection based on history and physical examination, which leads to antibiotic abuse,” she said.

Dr. Park and her colleagues in the pediatric pharyngitis management investigation sent surveys to a total of 2,000 randomly selected members of the American Academy of Pediatrics (1,000 recipients) and the American Academy of Family Physicians (1,000 recipients).

The surveys included questions about demographics, management strategies for acute pharyngitis, understanding of the appropriate use of throat cultures and rapid testing, and the approach to a clinical scenario with clinical findings consistent with group A streptococci pharyngitis.

The preliminary results are based on the responses from 260 pediatricians and 245 family physicians. Approximately 94% of the physicians cited acute rheumatic fever prevention as a reason to treat bacterial pharyngitis, and 54% cited prevention of acute glomerulonephritis.

Rapid antigen detection tests were available to 89% of the physicians, and throat culture was available to 93%.

Of the 441 physicians who reported using any test, 39 (9%) said that they continued with antibiotic therapy despite a negative test, “which is why presumptively starting therapy pending results of a culture is discouraged; treatment often continues regardless of the result,” Dr. Park explained.

Also, 52 of the 388 physicians (13%) who reported using the rapid test said they did not confirm a negative result with throat culture, as current clinical guidelines recommend.

The findings are disappointing in light of the growing awareness of the risks of antibiotic overuse and resistance, said Dr. Park. “Accurate diagnosis of group A streptococcal pharyngitis and appropriate antimicrobial therapy are important, particularly to prevent nonsuppurative sequelae such as rheumatic fever. But following recommended guidelines is just as important.” Toward this end, more efforts need to target physician understanding of the appropriate use of throat culture and rapid antigen-detection testing to promote reasonable antibiotic prescribing.

BOSTON — Many physicians do not follow recommended guidelines for the diagnosis and management of children with pharyngitis, according to the results of a Centers for Disease Control and Prevention survey.

Although pharyngitis is one of the most common reasons for prescribing antibiotics, only 15%–30% of pediatric episodes are caused by group A streptococci and helped by antibiotics, CDC epidemiologist Sarah Y. Park, M.D., said in a presentation at the annual meeting of the Infectious Diseases Society of America.

Numerous studies have demonstrated that it is not possible on clinical grounds to differentiate streptococcal from viral pharyngitis, yet 278 of 505 eligible pediatricians and family medicine physicians (55%) who completed the CDC survey said they did not wait for laboratory confirmation of bacterial pharyngitis before initiating antibiotic therapy.

In addition, 64 of the respondents (13%) said they prescribed antibiotics based on clinical findings alone.

Diagnostic recommendations for pharyngitis are throat culture alone or a rapid antigen-detection test with throat culture backup, in conjunction with clinical and epidemiologic findings, said Dr. Park. “Diagnosis based on clinical findings alone is not recommended.

Most physicians tend to overestimate the probability of a streptococcal infection based on history and physical examination, which leads to antibiotic abuse,” she said.

Dr. Park and her colleagues in the pediatric pharyngitis management investigation sent surveys to a total of 2,000 randomly selected members of the American Academy of Pediatrics (1,000 recipients) and the American Academy of Family Physicians (1,000 recipients).

The surveys included questions about demographics, management strategies for acute pharyngitis, understanding of the appropriate use of throat cultures and rapid testing, and the approach to a clinical scenario with clinical findings consistent with group A streptococci pharyngitis.

The preliminary results are based on the responses from 260 pediatricians and 245 family physicians. Approximately 94% of the physicians cited acute rheumatic fever prevention as a reason to treat bacterial pharyngitis, and 54% cited prevention of acute glomerulonephritis.

Rapid antigen detection tests were available to 89% of the physicians, and throat culture was available to 93%.

Of the 441 physicians who reported using any test, 39 (9%) said that they continued with antibiotic therapy despite a negative test, “which is why presumptively starting therapy pending results of a culture is discouraged; treatment often continues regardless of the result,” Dr. Park explained.

Also, 52 of the 388 physicians (13%) who reported using the rapid test said they did not confirm a negative result with throat culture, as current clinical guidelines recommend.

The findings are disappointing in light of the growing awareness of the risks of antibiotic overuse and resistance, said Dr. Park. “Accurate diagnosis of group A streptococcal pharyngitis and appropriate antimicrobial therapy are important, particularly to prevent nonsuppurative sequelae such as rheumatic fever. But following recommended guidelines is just as important.” Toward this end, more efforts need to target physician understanding of the appropriate use of throat culture and rapid antigen-detection testing to promote reasonable antibiotic prescribing.

BOSTON — Many physicians do not follow recommended guidelines for the diagnosis and management of children with pharyngitis, according to the results of a Centers for Disease Control and Prevention survey.

Although pharyngitis is one of the most common reasons for prescribing antibiotics, only 15%–30% of pediatric episodes are caused by group A streptococci and helped by antibiotics, CDC epidemiologist Sarah Y. Park, M.D., said in a presentation at the annual meeting of the Infectious Diseases Society of America.

Numerous studies have demonstrated that it is not possible on clinical grounds to differentiate streptococcal from viral pharyngitis, yet 278 of 505 eligible pediatricians and family medicine physicians (55%) who completed the CDC survey said they did not wait for laboratory confirmation of bacterial pharyngitis before initiating antibiotic therapy.

In addition, 64 of the respondents (13%) said they prescribed antibiotics based on clinical findings alone.

Diagnostic recommendations for pharyngitis are throat culture alone or a rapid antigen-detection test with throat culture backup, in conjunction with clinical and epidemiologic findings, said Dr. Park. “Diagnosis based on clinical findings alone is not recommended.

Most physicians tend to overestimate the probability of a streptococcal infection based on history and physical examination, which leads to antibiotic abuse,” she said.

Dr. Park and her colleagues in the pediatric pharyngitis management investigation sent surveys to a total of 2,000 randomly selected members of the American Academy of Pediatrics (1,000 recipients) and the American Academy of Family Physicians (1,000 recipients).

The surveys included questions about demographics, management strategies for acute pharyngitis, understanding of the appropriate use of throat cultures and rapid testing, and the approach to a clinical scenario with clinical findings consistent with group A streptococci pharyngitis.

The preliminary results are based on the responses from 260 pediatricians and 245 family physicians. Approximately 94% of the physicians cited acute rheumatic fever prevention as a reason to treat bacterial pharyngitis, and 54% cited prevention of acute glomerulonephritis.

Rapid antigen detection tests were available to 89% of the physicians, and throat culture was available to 93%.

Of the 441 physicians who reported using any test, 39 (9%) said that they continued with antibiotic therapy despite a negative test, “which is why presumptively starting therapy pending results of a culture is discouraged; treatment often continues regardless of the result,” Dr. Park explained.

Also, 52 of the 388 physicians (13%) who reported using the rapid test said they did not confirm a negative result with throat culture, as current clinical guidelines recommend.

The findings are disappointing in light of the growing awareness of the risks of antibiotic overuse and resistance, said Dr. Park. “Accurate diagnosis of group A streptococcal pharyngitis and appropriate antimicrobial therapy are important, particularly to prevent nonsuppurative sequelae such as rheumatic fever. But following recommended guidelines is just as important.” Toward this end, more efforts need to target physician understanding of the appropriate use of throat culture and rapid antigen-detection testing to promote reasonable antibiotic prescribing.