Diana Mahoney

Three new studies published in the British Medical Journal on the use of popular antidepressants and suicide risk in adults reach conflicting conclusions.

One study reviewed data from 702 randomized controlled clinical trials (87,650 patients) that compared selective serotonin reuptake inhibitors with placebos or other treatments in patients with various conditions, including depression, bulimia, panic disorder, and sexual dysfunction. The authors found that suicide attempts were twice as likely among patients taking the SSRIs than among those taking a placebo or receiving interventions other than tricyclics (BMJ 2005;330:396–9).

That finding suggests that patients who take antidepressants are more likely to talk about their suicidal thoughts or tell someone about their suicidal attempts—and in doing so, hopefully get help, David Fassler, M.D., a trustee of the American Psychiatric Association, told FAMILY PRACTICE NEWS.

When asked about his reaction to the BMJ studies, Rodrigo Muñoz, M.D., a psychiatrist who practices in San Diego, agreed that SSRIs could have the effect of increasing communications about suicide among patients. In addition, Dr. Muñoz also pointed to a recently published study of county-level suicide rates among adults (Arch. Gen. Psychiatr. 2005;62:165–72), in which SSRIs and other newer antidepressants were associated with lower suicide rates.

SSRIs have been under scrutiny over the last year amid concerns about an increased risk of suicidality among adolescents while on the drugs. Ultimately, those concerns prompted the Food and Drug Administration to order a black box warning for the medications, noting the potential risks in children and adolescents.

The findings published in BMJ did not show an increase in overall suicide attempts among SSRI users, compared with patients taking tricyclics. And an increased risk was not observed between SSRI use and placebo when only fatal suicides were considered.

“We documented a difference in absolute risk of 5.6 suicide attempts per 1,000 patient years of SSRI exposure, compared with placebo,” wrote Dean Fergusson, Ph.D., of the Ottawa Health Research Institute and his colleagues. “Although small, the incremental risk remains an important population health issue because of the widespread use of SSRIs.” This information should be relayed to physicians and patients, as long as the risk is kept in perspective relative to the benefits of the drugs, the authors stated.

Methodologic limitations among the published trials considered in this analysis may compromise the findings. For example, the risk of suicide attempts may be underestimated, the authors said. “We were unable to find documentation confirming or refuting suicide attempts in 51,205 of the 87,650 patients.”

Additionally, many of the trials only reported adverse events that occurred in excess of a prespecified threshold, leaving open the possibility of rare but lethal complications going unreported or underreported, the authors noted. And many of the randomized control trials considered small patient populations for short time periods, and as such were not designed to identify completed or attempted suicides, thus making it impossible to infer long-term risks and treatment benefits.

In fact, although pooling the data from hundreds of trials increased the overall numbers, the absolute numbers of patients attempting and committing suicide remained very low, according to the authors of an accompanying editorial. This means that “reporting or not reporting a few cases could have completely changed the overall outcome,” wrote Andrea Cipriani, M.D., of the University of Verona (Italy) and her colleagues in an accompanying editorial (BMJ 2005;330:373–4).

Dr. Fassler said one of the problems with interpreting these findings is that it is difficult to tease out the methodologic details. “The current findings do not demonstrate that antidepressants are associated with an increased risk of suicide. This result is consistent with previous studies and should be reassuring to physicians and patients,” said Dr. Fassler, a clinical associate professor of psychiatry at the University of Vermont at Burlington.

The largest of the three new investigations was a nested case-control study based on the British general practice research database that assessed the risk of nonfatal self harm and suicide among 146,095 patients newly diagnosed with depression who received SSRIs or tricyclics (BMJ 2005;330:389–93).

“We found no evidence that the risk of suicide or nonfatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants,” reported Carlos Martinez, M.D., of the Medicines and Healthcare Products Regulatory Agency in London and his colleagues in the review.

The results of the third study—a metaanalysis of published and unpublished randomized control trials of SSRIs, compared with placebo, in about 40,000 adults submitted by drug companies to the safety review arm of the Medicines and Healthcare Products Regulatory Agency—are similarly vague and inconclusive. The authors determined that because of the low incidence of suicide, “it is not possible to rule out either a threefold increase or a decrease in its occurrence among people treated with SSRIs.” To detect an important effect on risk, an analysis would require large trials randomizing “around 2 million individuals,” according to David Gunnell, M.D., of the University of Bristol (England) and his colleagues in the study (BMJ 2005; 330:385–8).

“We found weak evidence of an increased risk of non-fatal self harm, but our results are compatible with either no reduction or a risk that is 2.5 times higher than in placebo-treated patients,” the authors wrote. The possible differences in risk in relation to self harm and suicidal thoughts is noteworthy, they stated. Though the differences could be attributable to chance given the relatively low number of events, they could also be a function of efficacy in treating depression. “The possible rise in self harm may result from a different mechanism, such as a disinhibiting effect of SSRIs in the early stages of treatment.”

The authors' conclusions echo those of most professionals in response to growing concern about the possible connection between suicide risk and SSRI treatment. “In view of the widespread prescribing of SSRIs and the possibility that they may increase the risk of suicidal behavior in some individuals, research is urgently needed both to clarify appropriate indications for their use and to determine whether it is possible to identify people at risk of possible suicidal side effects,” they wrote.

“There's no question that we need more studies on this issue. In particular, we need more long-term follow-up studies. Much of the data currently available are from relatively short-term clinical trials, yet for many people, depression is a chronic illness with multiple relapses. We need to know the risk and benefits of treatment over time,” Dr. Fassler said. “From the child literature, we know that over 40% of young people diagnosed with depression will eventually attempt suicide, and over 3% will ultimately die as a result. But research has also demonstrated that we can reduce suicidal ideation and the risk of relapse with effective and appropriate treatment.”

Several studies funded by the National Institute of Mental Health are underway that will provide insight into the many variables that contribute to suicidal thinking and behavior, “and we have made considerable progress in terms of access to data from clinical trials,” said Dr. Fassler, referring to the growing momentum in support of a centralized public registry.

The new studies “add to the larger and ongoing discussion” about the FDA's ability to evaluate drug dangerousness, Dr. Fassler said. “It's clear that this is a complex issue with no easy answers. The more information we have, the better.”

Three new studies published in the British Medical Journal on the use of popular antidepressants and suicide risk in adults reach conflicting conclusions.

One study reviewed data from 702 randomized controlled clinical trials (87,650 patients) that compared selective serotonin reuptake inhibitors with placebos or other treatments in patients with various conditions, including depression, bulimia, panic disorder, and sexual dysfunction. The authors found that suicide attempts were twice as likely among patients taking the SSRIs than among those taking a placebo or receiving interventions other than tricyclics (BMJ 2005;330:396–9).

That finding suggests that patients who take antidepressants are more likely to talk about their suicidal thoughts or tell someone about their suicidal attempts—and in doing so, hopefully get help, David Fassler, M.D., a trustee of the American Psychiatric Association, told FAMILY PRACTICE NEWS.

When asked about his reaction to the BMJ studies, Rodrigo Muñoz, M.D., a psychiatrist who practices in San Diego, agreed that SSRIs could have the effect of increasing communications about suicide among patients. In addition, Dr. Muñoz also pointed to a recently published study of county-level suicide rates among adults (Arch. Gen. Psychiatr. 2005;62:165–72), in which SSRIs and other newer antidepressants were associated with lower suicide rates.

SSRIs have been under scrutiny over the last year amid concerns about an increased risk of suicidality among adolescents while on the drugs. Ultimately, those concerns prompted the Food and Drug Administration to order a black box warning for the medications, noting the potential risks in children and adolescents.

The findings published in BMJ did not show an increase in overall suicide attempts among SSRI users, compared with patients taking tricyclics. And an increased risk was not observed between SSRI use and placebo when only fatal suicides were considered.

“We documented a difference in absolute risk of 5.6 suicide attempts per 1,000 patient years of SSRI exposure, compared with placebo,” wrote Dean Fergusson, Ph.D., of the Ottawa Health Research Institute and his colleagues. “Although small, the incremental risk remains an important population health issue because of the widespread use of SSRIs.” This information should be relayed to physicians and patients, as long as the risk is kept in perspective relative to the benefits of the drugs, the authors stated.

Methodologic limitations among the published trials considered in this analysis may compromise the findings. For example, the risk of suicide attempts may be underestimated, the authors said. “We were unable to find documentation confirming or refuting suicide attempts in 51,205 of the 87,650 patients.”

Additionally, many of the trials only reported adverse events that occurred in excess of a prespecified threshold, leaving open the possibility of rare but lethal complications going unreported or underreported, the authors noted. And many of the randomized control trials considered small patient populations for short time periods, and as such were not designed to identify completed or attempted suicides, thus making it impossible to infer long-term risks and treatment benefits.

In fact, although pooling the data from hundreds of trials increased the overall numbers, the absolute numbers of patients attempting and committing suicide remained very low, according to the authors of an accompanying editorial. This means that “reporting or not reporting a few cases could have completely changed the overall outcome,” wrote Andrea Cipriani, M.D., of the University of Verona (Italy) and her colleagues in an accompanying editorial (BMJ 2005;330:373–4).

Dr. Fassler said one of the problems with interpreting these findings is that it is difficult to tease out the methodologic details. “The current findings do not demonstrate that antidepressants are associated with an increased risk of suicide. This result is consistent with previous studies and should be reassuring to physicians and patients,” said Dr. Fassler, a clinical associate professor of psychiatry at the University of Vermont at Burlington.

The largest of the three new investigations was a nested case-control study based on the British general practice research database that assessed the risk of nonfatal self harm and suicide among 146,095 patients newly diagnosed with depression who received SSRIs or tricyclics (BMJ 2005;330:389–93).

“We found no evidence that the risk of suicide or nonfatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants,” reported Carlos Martinez, M.D., of the Medicines and Healthcare Products Regulatory Agency in London and his colleagues in the review.

The results of the third study—a metaanalysis of published and unpublished randomized control trials of SSRIs, compared with placebo, in about 40,000 adults submitted by drug companies to the safety review arm of the Medicines and Healthcare Products Regulatory Agency—are similarly vague and inconclusive. The authors determined that because of the low incidence of suicide, “it is not possible to rule out either a threefold increase or a decrease in its occurrence among people treated with SSRIs.” To detect an important effect on risk, an analysis would require large trials randomizing “around 2 million individuals,” according to David Gunnell, M.D., of the University of Bristol (England) and his colleagues in the study (BMJ 2005; 330:385–8).

“We found weak evidence of an increased risk of non-fatal self harm, but our results are compatible with either no reduction or a risk that is 2.5 times higher than in placebo-treated patients,” the authors wrote. The possible differences in risk in relation to self harm and suicidal thoughts is noteworthy, they stated. Though the differences could be attributable to chance given the relatively low number of events, they could also be a function of efficacy in treating depression. “The possible rise in self harm may result from a different mechanism, such as a disinhibiting effect of SSRIs in the early stages of treatment.”

The authors' conclusions echo those of most professionals in response to growing concern about the possible connection between suicide risk and SSRI treatment. “In view of the widespread prescribing of SSRIs and the possibility that they may increase the risk of suicidal behavior in some individuals, research is urgently needed both to clarify appropriate indications for their use and to determine whether it is possible to identify people at risk of possible suicidal side effects,” they wrote.

“There's no question that we need more studies on this issue. In particular, we need more long-term follow-up studies. Much of the data currently available are from relatively short-term clinical trials, yet for many people, depression is a chronic illness with multiple relapses. We need to know the risk and benefits of treatment over time,” Dr. Fassler said. “From the child literature, we know that over 40% of young people diagnosed with depression will eventually attempt suicide, and over 3% will ultimately die as a result. But research has also demonstrated that we can reduce suicidal ideation and the risk of relapse with effective and appropriate treatment.”

Several studies funded by the National Institute of Mental Health are underway that will provide insight into the many variables that contribute to suicidal thinking and behavior, “and we have made considerable progress in terms of access to data from clinical trials,” said Dr. Fassler, referring to the growing momentum in support of a centralized public registry.

The new studies “add to the larger and ongoing discussion” about the FDA's ability to evaluate drug dangerousness, Dr. Fassler said. “It's clear that this is a complex issue with no easy answers. The more information we have, the better.”

Three new studies published in the British Medical Journal on the use of popular antidepressants and suicide risk in adults reach conflicting conclusions.

One study reviewed data from 702 randomized controlled clinical trials (87,650 patients) that compared selective serotonin reuptake inhibitors with placebos or other treatments in patients with various conditions, including depression, bulimia, panic disorder, and sexual dysfunction. The authors found that suicide attempts were twice as likely among patients taking the SSRIs than among those taking a placebo or receiving interventions other than tricyclics (BMJ 2005;330:396–9).

That finding suggests that patients who take antidepressants are more likely to talk about their suicidal thoughts or tell someone about their suicidal attempts—and in doing so, hopefully get help, David Fassler, M.D., a trustee of the American Psychiatric Association, told FAMILY PRACTICE NEWS.

When asked about his reaction to the BMJ studies, Rodrigo Muñoz, M.D., a psychiatrist who practices in San Diego, agreed that SSRIs could have the effect of increasing communications about suicide among patients. In addition, Dr. Muñoz also pointed to a recently published study of county-level suicide rates among adults (Arch. Gen. Psychiatr. 2005;62:165–72), in which SSRIs and other newer antidepressants were associated with lower suicide rates.

SSRIs have been under scrutiny over the last year amid concerns about an increased risk of suicidality among adolescents while on the drugs. Ultimately, those concerns prompted the Food and Drug Administration to order a black box warning for the medications, noting the potential risks in children and adolescents.

The findings published in BMJ did not show an increase in overall suicide attempts among SSRI users, compared with patients taking tricyclics. And an increased risk was not observed between SSRI use and placebo when only fatal suicides were considered.

“We documented a difference in absolute risk of 5.6 suicide attempts per 1,000 patient years of SSRI exposure, compared with placebo,” wrote Dean Fergusson, Ph.D., of the Ottawa Health Research Institute and his colleagues. “Although small, the incremental risk remains an important population health issue because of the widespread use of SSRIs.” This information should be relayed to physicians and patients, as long as the risk is kept in perspective relative to the benefits of the drugs, the authors stated.

Methodologic limitations among the published trials considered in this analysis may compromise the findings. For example, the risk of suicide attempts may be underestimated, the authors said. “We were unable to find documentation confirming or refuting suicide attempts in 51,205 of the 87,650 patients.”

Additionally, many of the trials only reported adverse events that occurred in excess of a prespecified threshold, leaving open the possibility of rare but lethal complications going unreported or underreported, the authors noted. And many of the randomized control trials considered small patient populations for short time periods, and as such were not designed to identify completed or attempted suicides, thus making it impossible to infer long-term risks and treatment benefits.

In fact, although pooling the data from hundreds of trials increased the overall numbers, the absolute numbers of patients attempting and committing suicide remained very low, according to the authors of an accompanying editorial. This means that “reporting or not reporting a few cases could have completely changed the overall outcome,” wrote Andrea Cipriani, M.D., of the University of Verona (Italy) and her colleagues in an accompanying editorial (BMJ 2005;330:373–4).

Dr. Fassler said one of the problems with interpreting these findings is that it is difficult to tease out the methodologic details. “The current findings do not demonstrate that antidepressants are associated with an increased risk of suicide. This result is consistent with previous studies and should be reassuring to physicians and patients,” said Dr. Fassler, a clinical associate professor of psychiatry at the University of Vermont at Burlington.

The largest of the three new investigations was a nested case-control study based on the British general practice research database that assessed the risk of nonfatal self harm and suicide among 146,095 patients newly diagnosed with depression who received SSRIs or tricyclics (BMJ 2005;330:389–93).

“We found no evidence that the risk of suicide or nonfatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants,” reported Carlos Martinez, M.D., of the Medicines and Healthcare Products Regulatory Agency in London and his colleagues in the review.

The results of the third study—a metaanalysis of published and unpublished randomized control trials of SSRIs, compared with placebo, in about 40,000 adults submitted by drug companies to the safety review arm of the Medicines and Healthcare Products Regulatory Agency—are similarly vague and inconclusive. The authors determined that because of the low incidence of suicide, “it is not possible to rule out either a threefold increase or a decrease in its occurrence among people treated with SSRIs.” To detect an important effect on risk, an analysis would require large trials randomizing “around 2 million individuals,” according to David Gunnell, M.D., of the University of Bristol (England) and his colleagues in the study (BMJ 2005; 330:385–8).

“We found weak evidence of an increased risk of non-fatal self harm, but our results are compatible with either no reduction or a risk that is 2.5 times higher than in placebo-treated patients,” the authors wrote. The possible differences in risk in relation to self harm and suicidal thoughts is noteworthy, they stated. Though the differences could be attributable to chance given the relatively low number of events, they could also be a function of efficacy in treating depression. “The possible rise in self harm may result from a different mechanism, such as a disinhibiting effect of SSRIs in the early stages of treatment.”

The authors' conclusions echo those of most professionals in response to growing concern about the possible connection between suicide risk and SSRI treatment. “In view of the widespread prescribing of SSRIs and the possibility that they may increase the risk of suicidal behavior in some individuals, research is urgently needed both to clarify appropriate indications for their use and to determine whether it is possible to identify people at risk of possible suicidal side effects,” they wrote.

“There's no question that we need more studies on this issue. In particular, we need more long-term follow-up studies. Much of the data currently available are from relatively short-term clinical trials, yet for many people, depression is a chronic illness with multiple relapses. We need to know the risk and benefits of treatment over time,” Dr. Fassler said. “From the child literature, we know that over 40% of young people diagnosed with depression will eventually attempt suicide, and over 3% will ultimately die as a result. But research has also demonstrated that we can reduce suicidal ideation and the risk of relapse with effective and appropriate treatment.”

Several studies funded by the National Institute of Mental Health are underway that will provide insight into the many variables that contribute to suicidal thinking and behavior, “and we have made considerable progress in terms of access to data from clinical trials,” said Dr. Fassler, referring to the growing momentum in support of a centralized public registry.

The new studies “add to the larger and ongoing discussion” about the FDA's ability to evaluate drug dangerousness, Dr. Fassler said. “It's clear that this is a complex issue with no easy answers. The more information we have, the better.”

STOWE, VT.—Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

Although much attention is given to the identification and treatment of head lice, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes rather than head hair. When they are not feeding, they hide in the seams of clothing and possibly the folds of bedding. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks can be signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations. Worldwide, infestations are common during times of war, in impoverished areas, and as a consequence of natural disasters that lead to living in crowded unsanitary conditions where clothing is not changed or laundered, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

The treatment of body lice focuses on the infested clothing. Removing the clothing, laundering it in hot water, drying it on high heat, and pressing it with a hot iron are generally effective, but these tactics are often not feasible in the areas in which they are most needed, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful.

Single-dose oral ivermectin has shown promise as an agent for mass treatment in the case of a widespread outbreak. Body lice may also respond to oral or topically applied pediculicides, although none of these agents are labeled or marketed for treatment of body lice in the United States.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short, crablike bodies. Although they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “eyelash nits are usually a manifestation of pubic louse infestation, not head louse infestation. I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, and, as such, may be associated with other sexually transmitted diseases. Pubic lice may also be acquired by sharing a bed with an infested person. Children with pubic lice “have usually been infected [through] contact with an infested adult,” the manner of which should be investigated, Dr. Elston said.

Particular care should be taken when pubic lice infestation is diagnosed as part of a rape investigation. “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. As such, mechanical removal of as many lice as possible may be important for evidentiary purposes.

Because the pubic louse egg is totally encased by a proteinaceous sheath, except for the operculum through which it feeds, it is more resistant to topical therapies than is the head louse. “The [egg] is relatively impermeable, so the best way to get to it is through the [host's] blood,” Dr. Elston said. Thus, oral sulfa drugs as well as ivermectin have been successful.

STOWE, VT.—Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

Although much attention is given to the identification and treatment of head lice, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes rather than head hair. When they are not feeding, they hide in the seams of clothing and possibly the folds of bedding. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks can be signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations. Worldwide, infestations are common during times of war, in impoverished areas, and as a consequence of natural disasters that lead to living in crowded unsanitary conditions where clothing is not changed or laundered, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

The treatment of body lice focuses on the infested clothing. Removing the clothing, laundering it in hot water, drying it on high heat, and pressing it with a hot iron are generally effective, but these tactics are often not feasible in the areas in which they are most needed, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful.

Single-dose oral ivermectin has shown promise as an agent for mass treatment in the case of a widespread outbreak. Body lice may also respond to oral or topically applied pediculicides, although none of these agents are labeled or marketed for treatment of body lice in the United States.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short, crablike bodies. Although they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “eyelash nits are usually a manifestation of pubic louse infestation, not head louse infestation. I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, and, as such, may be associated with other sexually transmitted diseases. Pubic lice may also be acquired by sharing a bed with an infested person. Children with pubic lice “have usually been infected [through] contact with an infested adult,” the manner of which should be investigated, Dr. Elston said.

Particular care should be taken when pubic lice infestation is diagnosed as part of a rape investigation. “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. As such, mechanical removal of as many lice as possible may be important for evidentiary purposes.

Because the pubic louse egg is totally encased by a proteinaceous sheath, except for the operculum through which it feeds, it is more resistant to topical therapies than is the head louse. “The [egg] is relatively impermeable, so the best way to get to it is through the [host's] blood,” Dr. Elston said. Thus, oral sulfa drugs as well as ivermectin have been successful.

STOWE, VT.—Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

Although much attention is given to the identification and treatment of head lice, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes rather than head hair. When they are not feeding, they hide in the seams of clothing and possibly the folds of bedding. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks can be signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations. Worldwide, infestations are common during times of war, in impoverished areas, and as a consequence of natural disasters that lead to living in crowded unsanitary conditions where clothing is not changed or laundered, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

The treatment of body lice focuses on the infested clothing. Removing the clothing, laundering it in hot water, drying it on high heat, and pressing it with a hot iron are generally effective, but these tactics are often not feasible in the areas in which they are most needed, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful.

Single-dose oral ivermectin has shown promise as an agent for mass treatment in the case of a widespread outbreak. Body lice may also respond to oral or topically applied pediculicides, although none of these agents are labeled or marketed for treatment of body lice in the United States.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short, crablike bodies. Although they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “eyelash nits are usually a manifestation of pubic louse infestation, not head louse infestation. I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, and, as such, may be associated with other sexually transmitted diseases. Pubic lice may also be acquired by sharing a bed with an infested person. Children with pubic lice “have usually been infected [through] contact with an infested adult,” the manner of which should be investigated, Dr. Elston said.

Particular care should be taken when pubic lice infestation is diagnosed as part of a rape investigation. “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. As such, mechanical removal of as many lice as possible may be important for evidentiary purposes.

Because the pubic louse egg is totally encased by a proteinaceous sheath, except for the operculum through which it feeds, it is more resistant to topical therapies than is the head louse. “The [egg] is relatively impermeable, so the best way to get to it is through the [host's] blood,” Dr. Elston said. Thus, oral sulfa drugs as well as ivermectin have been successful.

STOWE, VT.—Aggressive therapy upon presentation can improve the mortality and morbidity associated with septic shock, according to Stephen Leffler, M.D.

Early appropriate antibiotics, rapid fluid resuscitation, and timely use of vasopressors can improve outcome substantially, Dr. Leffler said in a presentation on sepsis management at an emergency medicine update sponsored by the University of Vermont. Options for the most critical patients also include blood transfusions, intubation/paralysis, activated protein C, and corticosteroids.

Standard emergency department therapy for patients presenting in septic shock typically includes hemodynamic support and appropriate antibiotics, with more targeted aggressive therapy being delayed until the patient is transferred to the intensive care unit, said Dr. Leffler of the university. Recent evidence suggests that holding off on the most aggressive therapy may result in early tissue hypoxia and irreversible tissue damage, while implementing standard ICU management techniques in the ED increases the likelihood of interrupting the destructive cascade.

An investigation of early goal-directed therapy (EGT) at Henry Ford Hospital in Detroit showed that using central venous oxygen saturation (ScvO2) and pressure, measured continuously by central venous cannulation, to balance systemic oxygen delivery and consumption during the first 6 hours after presentation can significantly reduce mortality in patients with septic shock.

In the 2002 study, 236 emergency department patients with septic shock were randomized to receive either usual care or the EGT protocol. All of the patients received arterial and venous catheters. The patients in the control group were transferred to the ICU and treated according to clinician discretion. The patients who were randomized to EGT received a central line for measurement of ScvO2 and were managed in the emergency department for 6 hours before being transported to the ICU.

The EGT protocol included providing a 500-mL bolus of fluid every 30 minutes as needed to maintain central venous pressure between 8 and 12 mm Hg, administering vasopressors in the presence of mean arterial pressures less than 65 mm Hg, and giving blood transfusions to keep hematocrit levels greater than 30% if ScvO2 was below 70%. After transfusion, if ScvO2 persisted at less than 70%, the patients received dobutamine and in some cases were intubated and paralyzed to decrease oxygen consumption.

Patients in the intervention group had a 30% hospital mortality, compared with 46% for those receiving standard therapy. “The EGT group also had improved lactate, pH, and ScvO2 levels,” Dr. Leffler said.

“There are some important take-home messages in these findings, even if we're not going to get central venous oxygen saturation in every patient,” Dr. Leffler said. For example, patients in the EGT group received 5 L of fluid in the first 6 hours of treatment—1.5 L more than the standard therapy group. “This tells us that we are probably underhydrating these patients, and that we should be more aggressive with fluids. The standard 1,500 cc is not going to be enough,” he said.

Additionally, the blood transfusion rate was 64% for EGT patients, compared with 18% for the control group. The message in this, Dr. Leffler said, “is to go ahead and type and cross if the patient's [hematocrit] goes below 30%. A couple of units of blood might help.”

There was no difference in the rates of intubation and vasopressor use between the two groups.

While studies of similar management strategies implemented in the ICU have failed to show similar outcome improvements, “I think the critical element is the timing,” Dr. Leffler said. “The intervention in the emergency department was probably initiated earlier, before irreversible end-organ dysfunction.”

Specific subsets of patients in septic shock may also benefit from treatment with activated protein C or corticosteroids, Dr. Leffler said. “There is some evidence that treatment with [recombinant] activated protein C can reduce mortality in septic shock, but this benefit appears only in the sickest patients,” specifically those with respiratory and hemodynamic failure, who are at increased risk of death from sepsis, Dr. Leffler said.

To be effective, the drug must be administered within 24 hours of sepsis-induced failure, and it should not be considered for patients with coagulopathy because of the increased bleeding risk, he said.

The drug's high cost also is a caveat, Dr. Leffler said. “At $7,250 per dose, [activated protein C] is not yet used routinely and won't be until more evidence shows it to be far better than other options,” he contended.

Corticosteroids also have a role in sepsis management, but not the high-dose, short-course, broadly administered regimens of the 1970s that proved ineffective in later trials, he said.

Recent studies have shown that more than half of all septic patients could have a relative adrenal insufficiency that may be implicated in worse outcomes. In a study of patients with relative adrenal insufficiency—identified by a corticotrophin stimulation test on admission—those treated with steroids had lower 28-day mortality than did those randomized to receive placebo in addition to standard therapy.

“This tells us that steroids may have a place in the treatment of critically ill patients in septic shock, and that maybe we want to do stim tests more often to determine who might benefit from steroid therapy,” he said.

The bottom line, according to Dr. Leffler, is that there is a huge cost associated with sepsis, in terms of dollars and lives. “We can do more for these patients in the emergency department than getting antibiotics on board,” he said. “If we improve their hemodynamics—through fluids, vasopressors, and possibly steroids—we can improve their chances.”

STOWE, VT.—Aggressive therapy upon presentation can improve the mortality and morbidity associated with septic shock, according to Stephen Leffler, M.D.

Early appropriate antibiotics, rapid fluid resuscitation, and timely use of vasopressors can improve outcome substantially, Dr. Leffler said in a presentation on sepsis management at an emergency medicine update sponsored by the University of Vermont. Options for the most critical patients also include blood transfusions, intubation/paralysis, activated protein C, and corticosteroids.

Standard emergency department therapy for patients presenting in septic shock typically includes hemodynamic support and appropriate antibiotics, with more targeted aggressive therapy being delayed until the patient is transferred to the intensive care unit, said Dr. Leffler of the university. Recent evidence suggests that holding off on the most aggressive therapy may result in early tissue hypoxia and irreversible tissue damage, while implementing standard ICU management techniques in the ED increases the likelihood of interrupting the destructive cascade.

An investigation of early goal-directed therapy (EGT) at Henry Ford Hospital in Detroit showed that using central venous oxygen saturation (ScvO2) and pressure, measured continuously by central venous cannulation, to balance systemic oxygen delivery and consumption during the first 6 hours after presentation can significantly reduce mortality in patients with septic shock.

In the 2002 study, 236 emergency department patients with septic shock were randomized to receive either usual care or the EGT protocol. All of the patients received arterial and venous catheters. The patients in the control group were transferred to the ICU and treated according to clinician discretion. The patients who were randomized to EGT received a central line for measurement of ScvO2 and were managed in the emergency department for 6 hours before being transported to the ICU.

The EGT protocol included providing a 500-mL bolus of fluid every 30 minutes as needed to maintain central venous pressure between 8 and 12 mm Hg, administering vasopressors in the presence of mean arterial pressures less than 65 mm Hg, and giving blood transfusions to keep hematocrit levels greater than 30% if ScvO2 was below 70%. After transfusion, if ScvO2 persisted at less than 70%, the patients received dobutamine and in some cases were intubated and paralyzed to decrease oxygen consumption.

Patients in the intervention group had a 30% hospital mortality, compared with 46% for those receiving standard therapy. “The EGT group also had improved lactate, pH, and ScvO2 levels,” Dr. Leffler said.

“There are some important take-home messages in these findings, even if we're not going to get central venous oxygen saturation in every patient,” Dr. Leffler said. For example, patients in the EGT group received 5 L of fluid in the first 6 hours of treatment—1.5 L more than the standard therapy group. “This tells us that we are probably underhydrating these patients, and that we should be more aggressive with fluids. The standard 1,500 cc is not going to be enough,” he said.

Additionally, the blood transfusion rate was 64% for EGT patients, compared with 18% for the control group. The message in this, Dr. Leffler said, “is to go ahead and type and cross if the patient's [hematocrit] goes below 30%. A couple of units of blood might help.”

There was no difference in the rates of intubation and vasopressor use between the two groups.

While studies of similar management strategies implemented in the ICU have failed to show similar outcome improvements, “I think the critical element is the timing,” Dr. Leffler said. “The intervention in the emergency department was probably initiated earlier, before irreversible end-organ dysfunction.”

Specific subsets of patients in septic shock may also benefit from treatment with activated protein C or corticosteroids, Dr. Leffler said. “There is some evidence that treatment with [recombinant] activated protein C can reduce mortality in septic shock, but this benefit appears only in the sickest patients,” specifically those with respiratory and hemodynamic failure, who are at increased risk of death from sepsis, Dr. Leffler said.

To be effective, the drug must be administered within 24 hours of sepsis-induced failure, and it should not be considered for patients with coagulopathy because of the increased bleeding risk, he said.

The drug's high cost also is a caveat, Dr. Leffler said. “At $7,250 per dose, [activated protein C] is not yet used routinely and won't be until more evidence shows it to be far better than other options,” he contended.

Corticosteroids also have a role in sepsis management, but not the high-dose, short-course, broadly administered regimens of the 1970s that proved ineffective in later trials, he said.

Recent studies have shown that more than half of all septic patients could have a relative adrenal insufficiency that may be implicated in worse outcomes. In a study of patients with relative adrenal insufficiency—identified by a corticotrophin stimulation test on admission—those treated with steroids had lower 28-day mortality than did those randomized to receive placebo in addition to standard therapy.

“This tells us that steroids may have a place in the treatment of critically ill patients in septic shock, and that maybe we want to do stim tests more often to determine who might benefit from steroid therapy,” he said.

The bottom line, according to Dr. Leffler, is that there is a huge cost associated with sepsis, in terms of dollars and lives. “We can do more for these patients in the emergency department than getting antibiotics on board,” he said. “If we improve their hemodynamics—through fluids, vasopressors, and possibly steroids—we can improve their chances.”

STOWE, VT.—Aggressive therapy upon presentation can improve the mortality and morbidity associated with septic shock, according to Stephen Leffler, M.D.

Early appropriate antibiotics, rapid fluid resuscitation, and timely use of vasopressors can improve outcome substantially, Dr. Leffler said in a presentation on sepsis management at an emergency medicine update sponsored by the University of Vermont. Options for the most critical patients also include blood transfusions, intubation/paralysis, activated protein C, and corticosteroids.

Standard emergency department therapy for patients presenting in septic shock typically includes hemodynamic support and appropriate antibiotics, with more targeted aggressive therapy being delayed until the patient is transferred to the intensive care unit, said Dr. Leffler of the university. Recent evidence suggests that holding off on the most aggressive therapy may result in early tissue hypoxia and irreversible tissue damage, while implementing standard ICU management techniques in the ED increases the likelihood of interrupting the destructive cascade.

An investigation of early goal-directed therapy (EGT) at Henry Ford Hospital in Detroit showed that using central venous oxygen saturation (ScvO2) and pressure, measured continuously by central venous cannulation, to balance systemic oxygen delivery and consumption during the first 6 hours after presentation can significantly reduce mortality in patients with septic shock.

In the 2002 study, 236 emergency department patients with septic shock were randomized to receive either usual care or the EGT protocol. All of the patients received arterial and venous catheters. The patients in the control group were transferred to the ICU and treated according to clinician discretion. The patients who were randomized to EGT received a central line for measurement of ScvO2 and were managed in the emergency department for 6 hours before being transported to the ICU.

The EGT protocol included providing a 500-mL bolus of fluid every 30 minutes as needed to maintain central venous pressure between 8 and 12 mm Hg, administering vasopressors in the presence of mean arterial pressures less than 65 mm Hg, and giving blood transfusions to keep hematocrit levels greater than 30% if ScvO2 was below 70%. After transfusion, if ScvO2 persisted at less than 70%, the patients received dobutamine and in some cases were intubated and paralyzed to decrease oxygen consumption.

Patients in the intervention group had a 30% hospital mortality, compared with 46% for those receiving standard therapy. “The EGT group also had improved lactate, pH, and ScvO2 levels,” Dr. Leffler said.

“There are some important take-home messages in these findings, even if we're not going to get central venous oxygen saturation in every patient,” Dr. Leffler said. For example, patients in the EGT group received 5 L of fluid in the first 6 hours of treatment—1.5 L more than the standard therapy group. “This tells us that we are probably underhydrating these patients, and that we should be more aggressive with fluids. The standard 1,500 cc is not going to be enough,” he said.

Additionally, the blood transfusion rate was 64% for EGT patients, compared with 18% for the control group. The message in this, Dr. Leffler said, “is to go ahead and type and cross if the patient's [hematocrit] goes below 30%. A couple of units of blood might help.”

There was no difference in the rates of intubation and vasopressor use between the two groups.

While studies of similar management strategies implemented in the ICU have failed to show similar outcome improvements, “I think the critical element is the timing,” Dr. Leffler said. “The intervention in the emergency department was probably initiated earlier, before irreversible end-organ dysfunction.”

Specific subsets of patients in septic shock may also benefit from treatment with activated protein C or corticosteroids, Dr. Leffler said. “There is some evidence that treatment with [recombinant] activated protein C can reduce mortality in septic shock, but this benefit appears only in the sickest patients,” specifically those with respiratory and hemodynamic failure, who are at increased risk of death from sepsis, Dr. Leffler said.

To be effective, the drug must be administered within 24 hours of sepsis-induced failure, and it should not be considered for patients with coagulopathy because of the increased bleeding risk, he said.

The drug's high cost also is a caveat, Dr. Leffler said. “At $7,250 per dose, [activated protein C] is not yet used routinely and won't be until more evidence shows it to be far better than other options,” he contended.

Corticosteroids also have a role in sepsis management, but not the high-dose, short-course, broadly administered regimens of the 1970s that proved ineffective in later trials, he said.

Recent studies have shown that more than half of all septic patients could have a relative adrenal insufficiency that may be implicated in worse outcomes. In a study of patients with relative adrenal insufficiency—identified by a corticotrophin stimulation test on admission—those treated with steroids had lower 28-day mortality than did those randomized to receive placebo in addition to standard therapy.

“This tells us that steroids may have a place in the treatment of critically ill patients in septic shock, and that maybe we want to do stim tests more often to determine who might benefit from steroid therapy,” he said.

The bottom line, according to Dr. Leffler, is that there is a huge cost associated with sepsis, in terms of dollars and lives. “We can do more for these patients in the emergency department than getting antibiotics on board,” he said. “If we improve their hemodynamics—through fluids, vasopressors, and possibly steroids—we can improve their chances.”

The combination of neuropathic signs, symptoms, and abnormal electrodiagnostic studies provides the most accurate diagnosis of distal symmetrical polyneuropathy, according to the authors of a new case definition for the noninflammatory nerve disease.

Considered independently, none of the triad offers perfect diagnostic accuracy in predicting the presence of the peripheral nervous system problem, wrote John D. England, M.D., and colleagues in the multidisciplinary Polyneuropathy Task Force. Yet various combinations of the three alter the degree of diagnostic certainty, which, for polyneuropathy, follows a continuum of probability, the authors stated (Neurology 2005;64:199–207).

The task force, comprising physician representatives from the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation, conducted a systematic literature review of prospective cohort surveys and case review studies. To determine the accuracy of the diagnostic predictors identified through the review, the panel calculated sensitivities and specificities of each, then rank-ordered, from highest to lowest, the likelihood of a positive diagnosis given various combinations of the predictors. They determined, for example, that the highest likelihood of distal symmetric polyneuropathy occurs with a combination of multiple symptoms, multiple signs, and abnormal electrophysiologic studies. Additionally, when multiple symptoms and signs are present but electrophysiologic findings are not available, the likelihood is downgraded to modest, and when signs are discordant with electrophysiologic findings, the likelihood of a positive diagnosis is further diminished.

The evidence-based recommendations evolved from a treatment guideline into a case definition when the task force found the definition of polyneuropathy was inconsistent across the available studies, hampering comparisons, the authors wrote.

The absence of formal criteria for the diagnosis of distal symmetric polyneuropathy has hindered research, said Dr. England of Deaconess Billings (Mont.) Clinic.

Based on the literature review, data classification, and formal consensus process, the authors reached these conclusions:

▸ Neuropathic symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy. Multiple neuropathic symptoms are more accurate predictors than are single symptoms, and should be weighted as such.

▸ Signs are better predictors than are symptoms, and should be weighted as such.

▸ A single abnormality upon examination is less sensitive than multiple abnormalities; thus, physicians should look for combinations of signs.

▸ Relatively simple examinations have the same diagnostic accuracy as do complex scoring systems.

▸ The high degree of inconsistency among studies describing the accuracy of quantitative sensory testing precludes the inclusion of such testing in the case definition.

These conclusions were gleaned from studies specific to distal symmetric polyneuropathy. Using the evidence-based conclusions as its guide, the task force developed an ordered set of case definitions ranked from highest to lowest based on the likelihood of disease, depending on the presence or absence of specific signs, symptoms, and electrophysiological results. (See chart.)

Symptoms of distal symmetric polyneuropathy begin distally in the feet and may be sensory (numbness, burning, dysesthesias, allodynia, and prickling paresthesias), motor (often weakness in the distal legs), or both. On examination, signs of the condition include abnormalities of primary sensory modalities (pain, touch, hot, cold, vibration, and proprioception), motor system, tendon reflexes (especially depressed or absent ankle jerks), or autonomic system.

With respect to electrodiagnostic evaluations, they are recommended but not required to fulfill the case definition criteria. Of the options, nerve conduction studies (NCS) are the most informative, providing a sensitive measure of the functional status of sensory and motor nerve fibers and therefore adding a higher level of specificity to the diagnosis. For this reason, they should be included in the assessment of polyneuropathy, with the caveat that they are neither sensitive nor specific enough on their own to be exclusive diagnostic criteria, the authors wrote. Because no formal consensus exists regarding the best NCS protocol for diagnosing polyneuropathy, the task force developed recommendations based on electrophysiologic principles that combine the highest sensitivity, specificity, and efficiency for diagnosing distal symmetric polyneuropathy. (See sidebar.)

Quantitative sensory testing is not included as part of the final case definition because the sensitivities and specificities of the psychophysical tests vary considerably, and they have greater inherent variability, making standardization difficult, the authors noted. Also excluded are quantitative autonomic tests, because they are not routinely performed in all medical centers.

One possible limitation to the case definition is the reliance on evidence predominantly related to diabetic peripheral neuropathy, the most common and rigorously studied variety. Some “uncertainty exists with respect to the generalization of the case definition to distal symmetric polyneuropathy associated with other etiologies,” the authors wrote.

The new case definition should be particularly useful for clinical and epidemiologic research design and implementation, the authors wrote. Formalizing the case definition “will ensure greater consistency of case selection,” and will go a long way toward standardizing and facilitating clinical research, Dr. England said.

Clinical Findings Most Predictive of Distal Symmetrical Polyneuropathy

Protocol for Nerve Conduction Studies

The Polyneuropathy Task Force recommended the following protocol for a nerve conduction study (NCS):

▸ Sural sensory and peroneal motor NCSs should be performed in one lower extremity. Normal results from both studies preclude a diagnosis of distal symmetric polyneuropathy.

▸ Abnormal sural sensory or peroneal motor NCS results warrant an NCS of at least the ulnar sensory, median sensory, and ulnar motor nerves in one upper extremity and, if desired, a contralateral sural sensory and one tibial motor NCS. Examiners should be cognizant of the possibility of abnormal median and ulnar studies because of nerve compression at the wrist or ulnar neuropathy at the elbow.

▸ An absent response for any of the sensory or motor nerves studied warrants an NCS of the contralateral nerve.

▸ An absent peroneal motor response calls for an ipsilateral tibial motor NCS.

Minimal criteria for electrodiagnostics confirmation of distal symmetric polyneuropathy is an abnormality of any attribute of nerve conduction in two separate nerves, one of which must be the sural nerve.

The combination of neuropathic signs, symptoms, and abnormal electrodiagnostic studies provides the most accurate diagnosis of distal symmetrical polyneuropathy, according to the authors of a new case definition for the noninflammatory nerve disease.

Considered independently, none of the triad offers perfect diagnostic accuracy in predicting the presence of the peripheral nervous system problem, wrote John D. England, M.D., and colleagues in the multidisciplinary Polyneuropathy Task Force. Yet various combinations of the three alter the degree of diagnostic certainty, which, for polyneuropathy, follows a continuum of probability, the authors stated (Neurology 2005;64:199–207).

The task force, comprising physician representatives from the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation, conducted a systematic literature review of prospective cohort surveys and case review studies. To determine the accuracy of the diagnostic predictors identified through the review, the panel calculated sensitivities and specificities of each, then rank-ordered, from highest to lowest, the likelihood of a positive diagnosis given various combinations of the predictors. They determined, for example, that the highest likelihood of distal symmetric polyneuropathy occurs with a combination of multiple symptoms, multiple signs, and abnormal electrophysiologic studies. Additionally, when multiple symptoms and signs are present but electrophysiologic findings are not available, the likelihood is downgraded to modest, and when signs are discordant with electrophysiologic findings, the likelihood of a positive diagnosis is further diminished.

The evidence-based recommendations evolved from a treatment guideline into a case definition when the task force found the definition of polyneuropathy was inconsistent across the available studies, hampering comparisons, the authors wrote.

The absence of formal criteria for the diagnosis of distal symmetric polyneuropathy has hindered research, said Dr. England of Deaconess Billings (Mont.) Clinic.

Based on the literature review, data classification, and formal consensus process, the authors reached these conclusions:

▸ Neuropathic symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy. Multiple neuropathic symptoms are more accurate predictors than are single symptoms, and should be weighted as such.

▸ Signs are better predictors than are symptoms, and should be weighted as such.

▸ A single abnormality upon examination is less sensitive than multiple abnormalities; thus, physicians should look for combinations of signs.

▸ Relatively simple examinations have the same diagnostic accuracy as do complex scoring systems.

▸ The high degree of inconsistency among studies describing the accuracy of quantitative sensory testing precludes the inclusion of such testing in the case definition.

These conclusions were gleaned from studies specific to distal symmetric polyneuropathy. Using the evidence-based conclusions as its guide, the task force developed an ordered set of case definitions ranked from highest to lowest based on the likelihood of disease, depending on the presence or absence of specific signs, symptoms, and electrophysiological results. (See chart.)

Symptoms of distal symmetric polyneuropathy begin distally in the feet and may be sensory (numbness, burning, dysesthesias, allodynia, and prickling paresthesias), motor (often weakness in the distal legs), or both. On examination, signs of the condition include abnormalities of primary sensory modalities (pain, touch, hot, cold, vibration, and proprioception), motor system, tendon reflexes (especially depressed or absent ankle jerks), or autonomic system.

With respect to electrodiagnostic evaluations, they are recommended but not required to fulfill the case definition criteria. Of the options, nerve conduction studies (NCS) are the most informative, providing a sensitive measure of the functional status of sensory and motor nerve fibers and therefore adding a higher level of specificity to the diagnosis. For this reason, they should be included in the assessment of polyneuropathy, with the caveat that they are neither sensitive nor specific enough on their own to be exclusive diagnostic criteria, the authors wrote. Because no formal consensus exists regarding the best NCS protocol for diagnosing polyneuropathy, the task force developed recommendations based on electrophysiologic principles that combine the highest sensitivity, specificity, and efficiency for diagnosing distal symmetric polyneuropathy. (See sidebar.)

Quantitative sensory testing is not included as part of the final case definition because the sensitivities and specificities of the psychophysical tests vary considerably, and they have greater inherent variability, making standardization difficult, the authors noted. Also excluded are quantitative autonomic tests, because they are not routinely performed in all medical centers.

One possible limitation to the case definition is the reliance on evidence predominantly related to diabetic peripheral neuropathy, the most common and rigorously studied variety. Some “uncertainty exists with respect to the generalization of the case definition to distal symmetric polyneuropathy associated with other etiologies,” the authors wrote.

The new case definition should be particularly useful for clinical and epidemiologic research design and implementation, the authors wrote. Formalizing the case definition “will ensure greater consistency of case selection,” and will go a long way toward standardizing and facilitating clinical research, Dr. England said.

Clinical Findings Most Predictive of Distal Symmetrical Polyneuropathy

Protocol for Nerve Conduction Studies

The Polyneuropathy Task Force recommended the following protocol for a nerve conduction study (NCS):

▸ Sural sensory and peroneal motor NCSs should be performed in one lower extremity. Normal results from both studies preclude a diagnosis of distal symmetric polyneuropathy.

▸ Abnormal sural sensory or peroneal motor NCS results warrant an NCS of at least the ulnar sensory, median sensory, and ulnar motor nerves in one upper extremity and, if desired, a contralateral sural sensory and one tibial motor NCS. Examiners should be cognizant of the possibility of abnormal median and ulnar studies because of nerve compression at the wrist or ulnar neuropathy at the elbow.

▸ An absent response for any of the sensory or motor nerves studied warrants an NCS of the contralateral nerve.

▸ An absent peroneal motor response calls for an ipsilateral tibial motor NCS.

Minimal criteria for electrodiagnostics confirmation of distal symmetric polyneuropathy is an abnormality of any attribute of nerve conduction in two separate nerves, one of which must be the sural nerve.

The combination of neuropathic signs, symptoms, and abnormal electrodiagnostic studies provides the most accurate diagnosis of distal symmetrical polyneuropathy, according to the authors of a new case definition for the noninflammatory nerve disease.

Considered independently, none of the triad offers perfect diagnostic accuracy in predicting the presence of the peripheral nervous system problem, wrote John D. England, M.D., and colleagues in the multidisciplinary Polyneuropathy Task Force. Yet various combinations of the three alter the degree of diagnostic certainty, which, for polyneuropathy, follows a continuum of probability, the authors stated (Neurology 2005;64:199–207).

The task force, comprising physician representatives from the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation, conducted a systematic literature review of prospective cohort surveys and case review studies. To determine the accuracy of the diagnostic predictors identified through the review, the panel calculated sensitivities and specificities of each, then rank-ordered, from highest to lowest, the likelihood of a positive diagnosis given various combinations of the predictors. They determined, for example, that the highest likelihood of distal symmetric polyneuropathy occurs with a combination of multiple symptoms, multiple signs, and abnormal electrophysiologic studies. Additionally, when multiple symptoms and signs are present but electrophysiologic findings are not available, the likelihood is downgraded to modest, and when signs are discordant with electrophysiologic findings, the likelihood of a positive diagnosis is further diminished.

The evidence-based recommendations evolved from a treatment guideline into a case definition when the task force found the definition of polyneuropathy was inconsistent across the available studies, hampering comparisons, the authors wrote.

The absence of formal criteria for the diagnosis of distal symmetric polyneuropathy has hindered research, said Dr. England of Deaconess Billings (Mont.) Clinic.

Based on the literature review, data classification, and formal consensus process, the authors reached these conclusions:

▸ Neuropathic symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy. Multiple neuropathic symptoms are more accurate predictors than are single symptoms, and should be weighted as such.

▸ Signs are better predictors than are symptoms, and should be weighted as such.

▸ A single abnormality upon examination is less sensitive than multiple abnormalities; thus, physicians should look for combinations of signs.

▸ Relatively simple examinations have the same diagnostic accuracy as do complex scoring systems.

▸ The high degree of inconsistency among studies describing the accuracy of quantitative sensory testing precludes the inclusion of such testing in the case definition.

These conclusions were gleaned from studies specific to distal symmetric polyneuropathy. Using the evidence-based conclusions as its guide, the task force developed an ordered set of case definitions ranked from highest to lowest based on the likelihood of disease, depending on the presence or absence of specific signs, symptoms, and electrophysiological results. (See chart.)

Symptoms of distal symmetric polyneuropathy begin distally in the feet and may be sensory (numbness, burning, dysesthesias, allodynia, and prickling paresthesias), motor (often weakness in the distal legs), or both. On examination, signs of the condition include abnormalities of primary sensory modalities (pain, touch, hot, cold, vibration, and proprioception), motor system, tendon reflexes (especially depressed or absent ankle jerks), or autonomic system.

With respect to electrodiagnostic evaluations, they are recommended but not required to fulfill the case definition criteria. Of the options, nerve conduction studies (NCS) are the most informative, providing a sensitive measure of the functional status of sensory and motor nerve fibers and therefore adding a higher level of specificity to the diagnosis. For this reason, they should be included in the assessment of polyneuropathy, with the caveat that they are neither sensitive nor specific enough on their own to be exclusive diagnostic criteria, the authors wrote. Because no formal consensus exists regarding the best NCS protocol for diagnosing polyneuropathy, the task force developed recommendations based on electrophysiologic principles that combine the highest sensitivity, specificity, and efficiency for diagnosing distal symmetric polyneuropathy. (See sidebar.)

Quantitative sensory testing is not included as part of the final case definition because the sensitivities and specificities of the psychophysical tests vary considerably, and they have greater inherent variability, making standardization difficult, the authors noted. Also excluded are quantitative autonomic tests, because they are not routinely performed in all medical centers.

One possible limitation to the case definition is the reliance on evidence predominantly related to diabetic peripheral neuropathy, the most common and rigorously studied variety. Some “uncertainty exists with respect to the generalization of the case definition to distal symmetric polyneuropathy associated with other etiologies,” the authors wrote.

The new case definition should be particularly useful for clinical and epidemiologic research design and implementation, the authors wrote. Formalizing the case definition “will ensure greater consistency of case selection,” and will go a long way toward standardizing and facilitating clinical research, Dr. England said.

Clinical Findings Most Predictive of Distal Symmetrical Polyneuropathy

Protocol for Nerve Conduction Studies

The Polyneuropathy Task Force recommended the following protocol for a nerve conduction study (NCS):

▸ Sural sensory and peroneal motor NCSs should be performed in one lower extremity. Normal results from both studies preclude a diagnosis of distal symmetric polyneuropathy.

▸ Abnormal sural sensory or peroneal motor NCS results warrant an NCS of at least the ulnar sensory, median sensory, and ulnar motor nerves in one upper extremity and, if desired, a contralateral sural sensory and one tibial motor NCS. Examiners should be cognizant of the possibility of abnormal median and ulnar studies because of nerve compression at the wrist or ulnar neuropathy at the elbow.

▸ An absent response for any of the sensory or motor nerves studied warrants an NCS of the contralateral nerve.

▸ An absent peroneal motor response calls for an ipsilateral tibial motor NCS.

Minimal criteria for electrodiagnostics confirmation of distal symmetric polyneuropathy is an abnormality of any attribute of nerve conduction in two separate nerves, one of which must be the sural nerve.

STOWE, VT. — Initiating use of anticonvulsant therapy or switching antiepileptic drugs used may trigger life-threatening dermatoses, Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The dermatoses associated with antiepileptic drugs (AEDs) typically involve blistering or are exfoliative. Patients at greatest risk are those with the triad of fever, swelling, and point tenderness who have recently initiated or altered seizure medications, Dr. Elston said.

Although these conditions are rare, it is critical that neurologists be aware of their possible occurrence as well as the signs and symptoms of the potentially fatal, acute syndromes when prescribing the implicated agents, epileptologist Jacqueline French, M.D., told CLINICAL NEUROLOGY NEWS.

Neurologists can reduce the risk of these events by commencing all new medications at a low dose, avoiding rapid dose increases, steering clear of known or presumed cross-reactive agents in patients with a history of sensitivity to a particular agent, and directing patients to report all adverse events, according to Dr. French of the University of Pennsylvania in Philadelphia.

Patients may not link their rash to their epilepsy medication, and instead of reporting it to their neurologists, they may seek care from their primary care doctor or dermatologist.

During his presentation, Dr. Elston noted that the differential diagnoses for such patients should include anticonvulsant hypersensitivity syndrome, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN)—all of which can be fatal if not properly addressed. Time is critical for these patients, as their survival often depends on prompt recognition and appropriate multidisciplinary treatment, stressed Dr. Elston of Geisinger Medical Center, Danville, Pa.

The severe cutaneous manifestations noted are most commonly associated with the first-generation aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin).

However, SJS and TEN have also been reported with the second-generation agent lamotrigine, particularly when used in combination with valproic acid.

Valproic acid when used as antiseizure monotherapy alone has a low independent association with the skin eruptions, Dr. Elston said.

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 SJS or TEN. The former, associated with 5% mortality, 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.

When a diagnosis is confirmed, 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, Dr. Elston said.

“If you put a patient on an alternative antiseizure drug that has a high degree of cross-reactivity, not only is the eruption likely to recur, the course will probably be quicker and more devastating.”

Dr. French noted that when anticonvulsant therapy is withdrawn, there is no “one best” alternative medication for seizure control. “There are many options, but they depend on the patient's history and their seizure type,” she said.

While the newer-generation antiepileptic drugs have proved to be at least as effective as the older agents in most settings and are associated with fewer side effects and adverse events, care must still be taken when prescribing them to patients who have reacted to previous drugs.

Anecdotal reports linking gabapentin to recurrence of hypersensitivity syndrome, for example, suggest this second-generation drug should be avoided in patients with a previous sensitivity.

The coadministration of lamotrigine and valproate should be avoided as well, given the increased risk of TEN, according to Dr. French.

Dr. Elston noted that in addition to withdrawing the offending anticonvulsant, intravenous fluid replacement is a mainstay of therapy for these syndromes. For the more severe exfoliative conditions, symptomatic treatment is the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances.

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.

It has been hypothesized that the severe anticonvulsant-induced skin reactions might be associated with reactivation of human herpesvirus 6.

If research bears this out, neurologists and dermatologists will gain more insight into—as well as possible tools for—the prevention and treatment of these conditions.

This patient developed full-thickness necrosis of toxic epidermal necrolysis on the trunk.

A drug hypersensitivity reaction resulted in follicular prominence on this patient's arm. Photos courtesy Dr. Dirk M. Elston

STOWE, VT. — Initiating use of anticonvulsant therapy or switching antiepileptic drugs used may trigger life-threatening dermatoses, Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The dermatoses associated with antiepileptic drugs (AEDs) typically involve blistering or are exfoliative. Patients at greatest risk are those with the triad of fever, swelling, and point tenderness who have recently initiated or altered seizure medications, Dr. Elston said.

Although these conditions are rare, it is critical that neurologists be aware of their possible occurrence as well as the signs and symptoms of the potentially fatal, acute syndromes when prescribing the implicated agents, epileptologist Jacqueline French, M.D., told CLINICAL NEUROLOGY NEWS.

Neurologists can reduce the risk of these events by commencing all new medications at a low dose, avoiding rapid dose increases, steering clear of known or presumed cross-reactive agents in patients with a history of sensitivity to a particular agent, and directing patients to report all adverse events, according to Dr. French of the University of Pennsylvania in Philadelphia.

Patients may not link their rash to their epilepsy medication, and instead of reporting it to their neurologists, they may seek care from their primary care doctor or dermatologist.

During his presentation, Dr. Elston noted that the differential diagnoses for such patients should include anticonvulsant hypersensitivity syndrome, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN)—all of which can be fatal if not properly addressed. Time is critical for these patients, as their survival often depends on prompt recognition and appropriate multidisciplinary treatment, stressed Dr. Elston of Geisinger Medical Center, Danville, Pa.

The severe cutaneous manifestations noted are most commonly associated with the first-generation aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin).

However, SJS and TEN have also been reported with the second-generation agent lamotrigine, particularly when used in combination with valproic acid.

Valproic acid when used as antiseizure monotherapy alone has a low independent association with the skin eruptions, Dr. Elston said.

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 SJS or TEN. The former, associated with 5% mortality, 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.

When a diagnosis is confirmed, 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, Dr. Elston said.

“If you put a patient on an alternative antiseizure drug that has a high degree of cross-reactivity, not only is the eruption likely to recur, the course will probably be quicker and more devastating.”

Dr. French noted that when anticonvulsant therapy is withdrawn, there is no “one best” alternative medication for seizure control. “There are many options, but they depend on the patient's history and their seizure type,” she said.

While the newer-generation antiepileptic drugs have proved to be at least as effective as the older agents in most settings and are associated with fewer side effects and adverse events, care must still be taken when prescribing them to patients who have reacted to previous drugs.

Anecdotal reports linking gabapentin to recurrence of hypersensitivity syndrome, for example, suggest this second-generation drug should be avoided in patients with a previous sensitivity.

The coadministration of lamotrigine and valproate should be avoided as well, given the increased risk of TEN, according to Dr. French.

Dr. Elston noted that in addition to withdrawing the offending anticonvulsant, intravenous fluid replacement is a mainstay of therapy for these syndromes. For the more severe exfoliative conditions, symptomatic treatment is the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances.

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.

It has been hypothesized that the severe anticonvulsant-induced skin reactions might be associated with reactivation of human herpesvirus 6.

If research bears this out, neurologists and dermatologists will gain more insight into—as well as possible tools for—the prevention and treatment of these conditions.

This patient developed full-thickness necrosis of toxic epidermal necrolysis on the trunk.

A drug hypersensitivity reaction resulted in follicular prominence on this patient's arm. Photos courtesy Dr. Dirk M. Elston

STOWE, VT. — Initiating use of anticonvulsant therapy or switching antiepileptic drugs used may trigger life-threatening dermatoses, Dirk M. Elston, M.D., said at a dermatology conference sponsored by the University of Vermont.

The dermatoses associated with antiepileptic drugs (AEDs) typically involve blistering or are exfoliative. Patients at greatest risk are those with the triad of fever, swelling, and point tenderness who have recently initiated or altered seizure medications, Dr. Elston said.

Although these conditions are rare, it is critical that neurologists be aware of their possible occurrence as well as the signs and symptoms of the potentially fatal, acute syndromes when prescribing the implicated agents, epileptologist Jacqueline French, M.D., told CLINICAL NEUROLOGY NEWS.

Neurologists can reduce the risk of these events by commencing all new medications at a low dose, avoiding rapid dose increases, steering clear of known or presumed cross-reactive agents in patients with a history of sensitivity to a particular agent, and directing patients to report all adverse events, according to Dr. French of the University of Pennsylvania in Philadelphia.

Patients may not link their rash to their epilepsy medication, and instead of reporting it to their neurologists, they may seek care from their primary care doctor or dermatologist.

During his presentation, Dr. Elston noted that the differential diagnoses for such patients should include anticonvulsant hypersensitivity syndrome, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN)—all of which can be fatal if not properly addressed. Time is critical for these patients, as their survival often depends on prompt recognition and appropriate multidisciplinary treatment, stressed Dr. Elston of Geisinger Medical Center, Danville, Pa.

The severe cutaneous manifestations noted are most commonly associated with the first-generation aromatic-ring antiepileptic agents (carbamazepine, phenobarbital, and phenytoin).

However, SJS and TEN have also been reported with the second-generation agent lamotrigine, particularly when used in combination with valproic acid.

Valproic acid when used as antiseizure monotherapy alone has a low independent association with the skin eruptions, Dr. Elston said.

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 SJS or TEN. The former, associated with 5% mortality, 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.

When a diagnosis is confirmed, 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, Dr. Elston said.

“If you put a patient on an alternative antiseizure drug that has a high degree of cross-reactivity, not only is the eruption likely to recur, the course will probably be quicker and more devastating.”

Dr. French noted that when anticonvulsant therapy is withdrawn, there is no “one best” alternative medication for seizure control. “There are many options, but they depend on the patient's history and their seizure type,” she said.

While the newer-generation antiepileptic drugs have proved to be at least as effective as the older agents in most settings and are associated with fewer side effects and adverse events, care must still be taken when prescribing them to patients who have reacted to previous drugs.

Anecdotal reports linking gabapentin to recurrence of hypersensitivity syndrome, for example, suggest this second-generation drug should be avoided in patients with a previous sensitivity.

The coadministration of lamotrigine and valproate should be avoided as well, given the increased risk of TEN, according to Dr. French.

Dr. Elston noted that in addition to withdrawing the offending anticonvulsant, intravenous fluid replacement is a mainstay of therapy for these syndromes. For the more severe exfoliative conditions, symptomatic treatment is the same as for burns—debridement, dressings, growth factors, and aggressive monitoring for infection and for fluid and electrolyte disturbances.

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.

It has been hypothesized that the severe anticonvulsant-induced skin reactions might be associated with reactivation of human herpesvirus 6.

If research bears this out, neurologists and dermatologists will gain more insight into—as well as possible tools for—the prevention and treatment of these conditions.

This patient developed full-thickness necrosis of toxic epidermal necrolysis on the trunk.

A drug hypersensitivity reaction resulted in follicular prominence on this patient's arm. Photos courtesy Dr. Dirk M. Elston

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and zidovudine (AZT). Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels ranged from 0.8 to 47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro.

The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible that the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have already acquired HIV in utero or during birth. It also is possible exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and zidovudine (AZT). Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels ranged from 0.8 to 47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro.

The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible that the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have already acquired HIV in utero or during birth. It also is possible exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

BOSTON — High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's “surprising” findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end, Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and zidovudine (AZT). Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. “What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels” of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels ranged from 0.8 to 47 times the IC50 levels, which “was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be,” said Dr. Shapiro.

The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a “two-for-one” deal, he said. “It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible that the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly,” he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have already acquired HIV in utero or during birth. It also is possible exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

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, she 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.

Pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” Dr. Cremens said. “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. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder has been 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 of the treatments 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 frequently prescribed in the elderly, such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens explained.

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.

Anticonvulsant medications are increasingly being used as a safe and effective alternative to lithium because of their more tolerable side effect profile, she said.

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. Cardiovascular effects can also occur, she said.

When initial mood stabilizing treatment is insufficient, adjunctive treatment with atypical antipsychotic medications may be indicated. “Atypical antipsychotics have been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” Dr. Cremens said.

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.”

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population. “Elderly are at the highest risk for suicide, which is among the top 10 causes of death in this cohort. And suicide in bipolar illness occurs in 10%-20% of depressed patients,” Dr. Cremens said.

For drug-resistant severe depression or acute mania, electroconvulsive therapy has shown therapeutic benefit in some elderly patients. Maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely unless a medical problem arises, 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, she 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.

Pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” Dr. Cremens said. “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. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder has been 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 of the treatments 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 frequently prescribed in the elderly, such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens explained.

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.

Anticonvulsant medications are increasingly being used as a safe and effective alternative to lithium because of their more tolerable side effect profile, she said.

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. Cardiovascular effects can also occur, she said.

When initial mood stabilizing treatment is insufficient, adjunctive treatment with atypical antipsychotic medications may be indicated. “Atypical antipsychotics have been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” Dr. Cremens said.

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.”

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population. “Elderly are at the highest risk for suicide, which is among the top 10 causes of death in this cohort. And suicide in bipolar illness occurs in 10%-20% of depressed patients,” Dr. Cremens said.

For drug-resistant severe depression or acute mania, electroconvulsive therapy has shown therapeutic benefit in some elderly patients. Maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely unless a medical problem arises, 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, she 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.

Pharmacodynamic and pharmacokinetic changes in elderly patients alter prescribing patterns. “Elderly may respond to lower doses, and toxicity may occur earlier in treatment,” Dr. Cremens said. “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. The medications prescribed for comorbid medical illness further complicate the treatment process.

When an accurate diagnosis of bipolar disorder has been 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 of the treatments 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 frequently prescribed in the elderly, such as diuretics, NSAIDs, ACE inhibitors, and others,” Dr. Cremens explained.

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.

Anticonvulsant medications are increasingly being used as a safe and effective alternative to lithium because of their more tolerable side effect profile, she said.

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. Cardiovascular effects can also occur, she said.

When initial mood stabilizing treatment is insufficient, adjunctive treatment with atypical antipsychotic medications may be indicated. “Atypical antipsychotics have been widely used for treatment of mania and, more recently, shown to improve symptoms of depression,” Dr. Cremens said.

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.”

Aggressive treatment of the acute depressive state in elderly bipolar patients is critical, given the increased risk of suicide in this population. “Elderly are at the highest risk for suicide, which is among the top 10 causes of death in this cohort. And suicide in bipolar illness occurs in 10%-20% of depressed patients,” Dr. Cremens said.

For drug-resistant severe depression or acute mania, electroconvulsive therapy has shown therapeutic benefit in some elderly patients. Maintenance pharmacotherapy or electroconvulsive therapy should be used indefinitely unless a medical problem arises, Dr. Cremens said.

STOWE, VT. — Getting to the root of diffuse hair shedding requires uncovering and eliminating or treating the possible triggers, said Wilma F. Bergfeld, M.D.

“The key to optimal management of shedding, or telogen effluvium, is detective work,” Dr. Bergfeld said at a dermatology conference sponsored by the University of Vermont. “You can't make most diagnoses from the door. You have to get up close and really look at the scalp.”

Taking adequate time for a thorough history, determining whether the hair is coming out at the root or breaking off, acquiring hair and scalp samples for biopsy and culture in the absence of a well-defined trigger, and assessing hair density and loss patterns using hair-loss measurement scales can provide important clues, as can the results of laboratory tests, including complete blood count, comprehensive metabolic panel, mineral levels, and an androgen screen, said Dr. Bergfeld, head of the clinical research and dermatopathology sections at the Cleveland Clinic.

“Ask the patient to describe how much hair they think they shed and when they notice it most,” Dr. Bergfeld suggested. “And if a patient comes in with a bag of hair that she's lost, remember to ask her how long she's been collecting it.”

Ask patients when the hair loss began, if it has been consistent, and whether there's a family history, Dr. Bergfeld continued. Also note all medications the patient takes, routine hair care habits, and whether the patient has had recent medical problems, surgeries, or childbirth.

Sometimes, the hair-loss trigger may be something as easy to identify as a deficiency of dietary zinc or vitamin A. In such cases, “when the nutrients are replaced, the shedding disappears,” Dr. Bergfeld said. In other cases, however, multiple triggers may be responsible. The range of possibilities includes illness or infection, childbirth, drug reactions, metabolic events (such as iron-storage anemia), hormonal abnormalities, endocrine disorders, surgery, psychological stress, scalp disease, systemic disorders, or genetic conditions such as androgenic alopecia.

“Noticeable shedding usually begins within 2-4 weeks after the insult, or trigger, although it can be months in some cases,” Dr. Bergfeld said. “For example, significant shedding is common in young females post partum as a consequence of the trauma and hormonal changes associated with birthing, but breast-feeding can delay the shed by months.”

Patients should be reminded that some shedding of hair is normal. In most people, up to 20% of the scalp hair is in telogen at a given time. Telogen effluvium is triggered when a physiologic or other event causes a greater number of hairs to enter telogen at one time. Acute telogen effluvium is usually self-limiting as the trigger event doesn't recur, Dr. Bergfeld said. When this type of nonscarring hair loss is persistent, however, either the trigger has not been eliminated or there is a more pervasive underlying medical condition that warrants further evaluation, she noted.

Management should include education about the hair growth cycle, treatment of underlying nutritional deficiencies, and possibly a prescription for minoxidil to promote hair growth, she said. “Often what is most important is reassurance that the shedding will not lead to baldness and that hair is being replaced.”

STOWE, VT. — Getting to the root of diffuse hair shedding requires uncovering and eliminating or treating the possible triggers, said Wilma F. Bergfeld, M.D.

“The key to optimal management of shedding, or telogen effluvium, is detective work,” Dr. Bergfeld said at a dermatology conference sponsored by the University of Vermont. “You can't make most diagnoses from the door. You have to get up close and really look at the scalp.”

Taking adequate time for a thorough history, determining whether the hair is coming out at the root or breaking off, acquiring hair and scalp samples for biopsy and culture in the absence of a well-defined trigger, and assessing hair density and loss patterns using hair-loss measurement scales can provide important clues, as can the results of laboratory tests, including complete blood count, comprehensive metabolic panel, mineral levels, and an androgen screen, said Dr. Bergfeld, head of the clinical research and dermatopathology sections at the Cleveland Clinic.

“Ask the patient to describe how much hair they think they shed and when they notice it most,” Dr. Bergfeld suggested. “And if a patient comes in with a bag of hair that she's lost, remember to ask her how long she's been collecting it.”

Ask patients when the hair loss began, if it has been consistent, and whether there's a family history, Dr. Bergfeld continued. Also note all medications the patient takes, routine hair care habits, and whether the patient has had recent medical problems, surgeries, or childbirth.

Sometimes, the hair-loss trigger may be something as easy to identify as a deficiency of dietary zinc or vitamin A. In such cases, “when the nutrients are replaced, the shedding disappears,” Dr. Bergfeld said. In other cases, however, multiple triggers may be responsible. The range of possibilities includes illness or infection, childbirth, drug reactions, metabolic events (such as iron-storage anemia), hormonal abnormalities, endocrine disorders, surgery, psychological stress, scalp disease, systemic disorders, or genetic conditions such as androgenic alopecia.

“Noticeable shedding usually begins within 2-4 weeks after the insult, or trigger, although it can be months in some cases,” Dr. Bergfeld said. “For example, significant shedding is common in young females post partum as a consequence of the trauma and hormonal changes associated with birthing, but breast-feeding can delay the shed by months.”

Patients should be reminded that some shedding of hair is normal. In most people, up to 20% of the scalp hair is in telogen at a given time. Telogen effluvium is triggered when a physiologic or other event causes a greater number of hairs to enter telogen at one time. Acute telogen effluvium is usually self-limiting as the trigger event doesn't recur, Dr. Bergfeld said. When this type of nonscarring hair loss is persistent, however, either the trigger has not been eliminated or there is a more pervasive underlying medical condition that warrants further evaluation, she noted.

Management should include education about the hair growth cycle, treatment of underlying nutritional deficiencies, and possibly a prescription for minoxidil to promote hair growth, she said. “Often what is most important is reassurance that the shedding will not lead to baldness and that hair is being replaced.”

STOWE, VT. — Getting to the root of diffuse hair shedding requires uncovering and eliminating or treating the possible triggers, said Wilma F. Bergfeld, M.D.

“The key to optimal management of shedding, or telogen effluvium, is detective work,” Dr. Bergfeld said at a dermatology conference sponsored by the University of Vermont. “You can't make most diagnoses from the door. You have to get up close and really look at the scalp.”

Taking adequate time for a thorough history, determining whether the hair is coming out at the root or breaking off, acquiring hair and scalp samples for biopsy and culture in the absence of a well-defined trigger, and assessing hair density and loss patterns using hair-loss measurement scales can provide important clues, as can the results of laboratory tests, including complete blood count, comprehensive metabolic panel, mineral levels, and an androgen screen, said Dr. Bergfeld, head of the clinical research and dermatopathology sections at the Cleveland Clinic.

“Ask the patient to describe how much hair they think they shed and when they notice it most,” Dr. Bergfeld suggested. “And if a patient comes in with a bag of hair that she's lost, remember to ask her how long she's been collecting it.”

Ask patients when the hair loss began, if it has been consistent, and whether there's a family history, Dr. Bergfeld continued. Also note all medications the patient takes, routine hair care habits, and whether the patient has had recent medical problems, surgeries, or childbirth.

Sometimes, the hair-loss trigger may be something as easy to identify as a deficiency of dietary zinc or vitamin A. In such cases, “when the nutrients are replaced, the shedding disappears,” Dr. Bergfeld said. In other cases, however, multiple triggers may be responsible. The range of possibilities includes illness or infection, childbirth, drug reactions, metabolic events (such as iron-storage anemia), hormonal abnormalities, endocrine disorders, surgery, psychological stress, scalp disease, systemic disorders, or genetic conditions such as androgenic alopecia.

“Noticeable shedding usually begins within 2-4 weeks after the insult, or trigger, although it can be months in some cases,” Dr. Bergfeld said. “For example, significant shedding is common in young females post partum as a consequence of the trauma and hormonal changes associated with birthing, but breast-feeding can delay the shed by months.”

Patients should be reminded that some shedding of hair is normal. In most people, up to 20% of the scalp hair is in telogen at a given time. Telogen effluvium is triggered when a physiologic or other event causes a greater number of hairs to enter telogen at one time. Acute telogen effluvium is usually self-limiting as the trigger event doesn't recur, Dr. Bergfeld said. When this type of nonscarring hair loss is persistent, however, either the trigger has not been eliminated or there is a more pervasive underlying medical condition that warrants further evaluation, she noted.

Management should include education about the hair growth cycle, treatment of underlying nutritional deficiencies, and possibly a prescription for minoxidil to promote hair growth, she said. “Often what is most important is reassurance that the shedding will not lead to baldness and that hair is being replaced.”

STOWE, VT. — Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

While much attention is given to the identification and treatment of head lice because they are hyperendemic in many areas of the world, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes and bedding rather than head hair. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks are possible signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

Body lice infestations are treated by removing the clothing, laundering it in hot water, drying it on high heat, or pressing it with a hot iron. However, these tactics are often not feasible in outbreaks in other parts of the world, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful. In addition, single-dose ivermectin has shown promise for mass treatment, and pediculicides may be effective against body lice.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short crablike bodies. While they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, but may also be acquired by sharing a bed. Children usually contract pubic lice from an adult, which should be investigated, he said.

However, pubic lice help to solve crimes “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. Because the pubic louse egg “is relatively impermeable, the best way to get to it is through the [host's] blood,” Dr. Elston said. Toward that end, oral sulfa drugs as well as ivermectin have been used successfully.

STOWE, VT. — Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

While much attention is given to the identification and treatment of head lice because they are hyperendemic in many areas of the world, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes and bedding rather than head hair. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks are possible signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

Body lice infestations are treated by removing the clothing, laundering it in hot water, drying it on high heat, or pressing it with a hot iron. However, these tactics are often not feasible in outbreaks in other parts of the world, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful. In addition, single-dose ivermectin has shown promise for mass treatment, and pediculicides may be effective against body lice.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short crablike bodies. While they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, but may also be acquired by sharing a bed. Children usually contract pubic lice from an adult, which should be investigated, he said.

However, pubic lice help to solve crimes “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. Because the pubic louse egg “is relatively impermeable, the best way to get to it is through the [host's] blood,” Dr. Elston said. Toward that end, oral sulfa drugs as well as ivermectin have been used successfully.

STOWE, VT. — Location, location, location. Where lice live on the body and how they got there are important considerations for optimal diagnosis and therapy, according to Dirk M. Elston, M.D.

While much attention is given to the identification and treatment of head lice because they are hyperendemic in many areas of the world, body lice and pubic lice are unique entities with specific treatment requirements, Dr. Elston said at a dermatology conference sponsored by the University of Vermont.

Similar in appearance to head lice, body lice (Pediculus humanus corporis) live in clothes and bedding rather than head hair. Scratch marks, hives, and small raised red bumps on the shoulders, torso, or buttocks are possible signs of body lice infestation.

Unlike head lice, body lice can be vectors for blood-borne diseases such as typhus and trench fever. In the United States, body louse infestation mainly affects homeless populations, said Dr. Elston of Geisinger Medical Center, Danville, Pa.

Body lice infestations are treated by removing the clothing, laundering it in hot water, drying it on high heat, or pressing it with a hot iron. However, these tactics are often not feasible in outbreaks in other parts of the world, Dr. Elston said. In some settings, treating clothing with DDT, permethrin, or fumigants is useful. In addition, single-dose ivermectin has shown promise for mass treatment, and pediculicides may be effective against body lice.

Pubic lice (Phthirus pubis) are distinct in appearance from head and body lice; they have short crablike bodies. While they are most frequently found in the pubic region of the infested person, where they can cause intense itching and redness, they may also be found in other areas, such as in facial hair or eyelashes. In fact, Dr. Elston said, “I am amazed at how often it is misdiagnosed. When you see eyelash nits, you should be looking south, not north,” he stressed.

Pubic lice infestation occurs mainly through sexual contact, but may also be acquired by sharing a bed. Children usually contract pubic lice from an adult, which should be investigated, he said.

However, pubic lice help to solve crimes “There is enough blood in a single louse to identify a rapist's DNA by [polymerase chain reaction],” he said. Because the pubic louse egg “is relatively impermeable, the best way to get to it is through the [host's] blood,” Dr. Elston said. Toward that end, oral sulfa drugs as well as ivermectin have been used successfully.