Pediatrics

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Most patients who are receiving maintenance hemodialysis develop a good antibody response after being given two doses of the Pfizer-BioNTech COVID-19 vaccine, but their responses are still significantly lower than those of health care workers who do not have kidney disease, the first study of its kind shows.

“It is well known that patients on dialysis may have a reduced response to vaccination,” Ayelet Grupper, MD, of Tel Aviv Medical Center, and colleagues observe. Their study was published online April 6 in the Clinical Journal of the American Society of Nephrology.

“I believe our findings should encourage patients with kidney failure treated with dialysis to be vaccinated as soon as vaccination becomes available for them, while we as caregivers should explore ways to enhance its efficacy in our patients,” senior author Moshe Shashar, MD, noted in a statement from the American Society of Nephrology.

Asked to comment, Peter Blake, MD, professor of medicine, University of Western Ontario, London, pointed out that COVID-19 is very common among hemodialysis patients and that the likelihood of these patients dying from it is very high. Indeed, 1.5% of approximately 12,500 patients receiving dialysis in the province of Ontario have died of COVID-19 – “a horrifying statistic and one that only long-term care home residents can compare with,” he told this news organization.

In the Israeli study, almost all dialysis patients mounted a serologic response to the Pfizer-BioNTech vaccine, which is “good news” overall, Dr. Blake said.

Also commenting on the study, Anushree Shirali, MD, of Yale University, New Haven, Conn., said she was impressed by the fact that most of the dialysis patients in the study mounted at least some IgG response to vaccination, which she said was good “in and of itself,” because that is not always the case with other vaccines.
 

Study compared dialysis patients with health care workers

The Israeli study included 56 patients who were receiving maintenance hemodialysis and 95 health care workers, who served as control persons.

“All participants had been previously vaccinated with the [Pfizer-BioNTech] vaccine, with the recommended dosing interval of 21 days between the first and second doses,” the investigators note. Immunogenicity was assessed using a dedicated immunoassay to quantify the level of IgG antibodies from participants’ plasma.

A cutoff for a positive antibody response was greater than or equal to 50 arbitrary units per milliliter (AU/mL). “All subjects in the control group developed a positive antibody response (≥50 AU/mL) as compared with 96% (54 of 56) in the dialysis group,” Dr. Shashar and colleagues report.

The median IgG level in the dialysis group was 2,900 AU/mL, which is significantly lower than the median of 7,401 AU/mL in the control group (P < .001), they report.

The investigators also observed a significant inverse correlation between older age and antibody levels in both groups.

The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; P = .004) and for the dialysis group compared with the control group (OR, 2.7; P = .05).

Among the dialysis patients, older age and lower lymphocyte count were associated with antibody response in the lower quartile (OR, 1.22 per 1 year older; P = .03; and OR, 0.83 per 10-e3/mL-higher lymphocyte count; P = .05).

Among recipients older than 70 years, there was little difference in antibody response between the dialysis patients and the control group. Thus, age is clearly an important contributor to a robust humoral response, the authors observe.

For more than 90% of the patients receiving dialysis, the antibody response was well above 50 AU/mL, which was the cutoff for having a positive response.

Nevertheless, the authors suggest that their findings should prompt clinicians to consider either changing the dose or the schedule of COVID-19 vaccination for dialysis patients, as was done, for example, with the hepatitis B vaccine Engerix-B.

Dialysis patients now receive double doses of the hepatitis B vaccine, which is given in a four-series vaccine schedule rather than a three-series vaccine schedule, as is given to healthy individuals.

The authors also call for studies to assess the longevity of vaccine efficacy for dialysis patients and whether current vaccines are effective against variant strains among patients undergoing dialysis.
 

Some suggestion COVID-19 vaccines also elicit T-cell responses

Dr. Shirali said the news regarding the COVID-19 vaccine for dialysis patients is good, given the fact that such patients exhibit a poor response to the hepatitis B vaccine.

“There isn’t a large percentage of dialysis patients who mount a humoral response to the hepatitis B vaccine, even with the change in dosing that we use that is different than it is for the general population,” she told this news organization.

Dr. Shirali also noted that preliminary evidence suggests that COVID-19 vaccines elicit nonantibody and antibody T-cell responses and that such immunity is going to be just as important for protecting dialysis patients against COVID-19 as it is for protecting patients who are not receiving dialysis.

“Antibody responses are just one arm of vaccination,” she explained. “People can form memory T-cell responses with vaccination, and while this has not been well studied with COVID-19, there are preliminary data to suggest that T-cell responses are likely to be effective in the fight against COVID-19.” There is also the possibility that this type of response “may even be more durable than antibody responses,” she said.

The study received no funding. The authors, Dr. Blake and Dr. Shirali, have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

A punch biopsy from one of the lesions on the feet showed subtle basal vacuolar interface inflammation on the epidermis and rare apoptotic keratinocytes. There was an underlying dermal lymphocytic inflammatory infiltrate around the vascular plexus. Dermal mucin appeared slightly increased. The histologic findings are consistent with pernio. He had a negative direct immunofluorescence study.

Laboratory work-up showed an elevated antinuclear antibody (ANA) of 1:620; positive anticardiolipin IgM was at 15.2. A complete blood count showed no anemia or lymphopenia, he had normal complement C3 and C4 levels, normal urinalysis, negative cryoglobulins and cold agglutinins, and a normal protein electrophoresis.

Given the chronicity of his lesions, the lack of improvement with weather changes, the histopathologic findings of a vacuolar interface dermatitis and the positive ANA titer he was diagnosed with chilblain lupus.

Chilblain lupus erythematosus (CLE) is an uncommon form of chronic cutaneous lupus erythematosus that presents with tender pink to violaceous macules, papules, and/or nodules that sometimes can ulcerate and are present on the fingers, toes, and sometimes the nose and ears. The lesions are usually triggered by cold exposure.¹ These patients also have clinical and laboratory findings consistent with lupus erythematosus.

Even though more studies are needed to clarify the clinical and histopathologic features of chilblain lupus, compared with idiopathic pernio, some authors suggest several characteristics: CLE lesions tend to persist in summer months, as occurred in our patient, and histopathologic evaluation usually shows vacuolar and interface inflammation on the basal cell layer and may also have a positive lupus band on direct immunofluorescence.² About 20% of patient with CLE may later develop systemic lupus erythematosus.³

There is also a familial form of CLE which is usually inherited as an autosomal-dominant trait. Mutations in TREX1, SAMHD1, and STING have been described in these patients.⁴ Affected children present with skin lesions at a young age and those with TREX1 mutations are at a higher risk to develop systemic lupus erythematosus.

The differential diagnosis of chilblain lupus includes idiopathic pernio or pernio secondary to other conditions. Other conditions that are thought to be associated with pernio, besides lupus erythematosus, include infectious causes (hepatitis B, COVID-19 infection),⁵ autoimmune conditions, malignancy and hematologic disorders (paraproteinemia).⁶ In histopathology, pernio lesions present with dermal edema and superficial and deep lymphocytic infiltrate.

The pathogenesis of pernio is not fully understood but is thought be related to vasospasm with secondary poor perfusion and ischemia and type I interferon (INF1) immune response. A recent review of the published studies trying to explain the causality between COVID 19 and pernio-like lesions, from January 2020 to December 2020, speculate several possible mechanisms: an increase in the vasoconstrictive, prothrombotic, and proinflammatory effects of the angiotensin II pathway through activation of the ACE2 by the virus; COVID-19 triggers a robust INF1 immune response in predisposed patients; pernio as a sign of mild disease, may be explained by genetic and hormonal differences in the patients affected.⁷

Another condition that can be confused with CLE is Raynaud phenomenon, were patients present with white to purple to red patches on the fingers and toes after exposure to cold, but in comparison with pernio, the lesions improve within minutes to hours after rewarming. Secondary Raynaud phenomenon can be seen in patients with systemic lupus erythematosus and in patients with other connective tissue disorders. The skin lesions in our patient were persistent and were not triggered by cold exposure, making Raynaud phenomenon less likely. Children with vasculitis can present with painful red, violaceous, or necrotic lesions on the extremities, which can mimic pernio. Vasculitis lesions tend to be more purpuric and angulated, compared with pernio lesions, though in severe cases of pernio with ulceration it may be difficult to distinguish between the two entities and a skin biopsy may be needed.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin condition in which children present with edematous tender nodules on the hands and with less frequency in other parts of the body with associated fever, malaise, conjunctivitis, or joint pain and it is usually associated with infection or malignancy. Our patient denied any systemic symptoms and had no conjunctivitis nor arthritis.

Most patients with idiopathic pernio do not require a biopsy or further laboratory evaluation unless the lesions are atypical, chronic, or there is a suspected associated condition. The workup for patients with prolonged or atypical pernio-like lesions include a skin biopsy with direct immunofluorescence, ANA, complete blood count, complement levels, antiphospholipid antibodies, cold agglutinins, and cryoglobulins.

Treatment of mild CLE is with moderate- to high-potency topical corticosteroids. In those patients not responding to topical measures and keeping the extremities warm, the use of hydroxychloroquine has been reported to be beneficial in some patients as well as the use of calcium-channel blockers.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

1. Su WP et al. Cutis. 1994 Dec;54(6):395-9.

2. Boada A et al. Am J Dermatopathol. 2010 Feb;32(1):19-23.

3. Patel et al. SBMJ Case Rep. 2013;2013:bcr2013201165.

4. Genes Yi et al. BMC. 2020 Apr 15;18(1):32.

5. Battesti G et al. J Am Acad Dermatol. 2020;83(4):1219-22.

6. Cappel JA et al. Mayo Clin Proc. 2014 Feb;89(2):207-15.

7. Cappel MA et al. Mayo Clin Proc. 2021;96(4):989-1005.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

For intrapartum fetal surveillance, the old way may be the best way, according to a meta-analysis involving more than 118,000 patients.

Intermittent auscultation with a Pinard stethoscope and handheld Doppler was associated with a significantly lower risk of emergency cesarean deliveries than newer monitoring techniques without jeopardizing maternal or neonatal outcomes, reported lead author Bassel H. Al Wattar, MD, PhD, of University of Warwick, Coventry, England, and University College London Hospitals, and colleagues.

“Over the last 50 years, several newer surveillance methods have been evaluated, with varied uptake in practice,” the investigators wrote in the Canadian Medical Association Journal, noting that cardiotocography (CTG) is the most common method for high-risk pregnancies, typically coupled with at least one other modality, such as fetal scalp pH analysis (FBS), fetal pulse oximetry (FPO), or fetal heart electrocardiogram (STAN).

“Despite extensive investment in clinical research, the overall effectiveness of such methods in improving maternal and neonatal outcomes remains debatable as stillbirth rates have plateaued worldwide, while cesarean delivery rates continue to rise,” the investigators wrote. Previous meta-analyses have relied upon head-to-head comparisons of monitoring techniques and did not take into account effects on maternal and neonatal outcomes.

To address this knowledge gap, Dr. Al Wattar and colleagues conducted the present systematic review and meta-analysis, ultimately including 33 trials with 118,863 women who underwent intrapartum fetal surveillance, dating back to 1976. Ten surveillance types were evaluated, including intermittent auscultation with Pinard stethoscope and handheld Doppler, CTG with or without computer-aided decision models (cCTG), and CTG or cCTG combined with one or two other techniques, such as FBS, FPO, and STAN.

This revealed that intermittent auscultation outperformed all other techniques in terms of emergency cesarean deliveries and emergency cesarean deliveries because of fetal distress.

Specifically, intermittent auscultation significantly reduced risk of emergency cesarean deliveries, compared with CTG (relative risk, 0.83; 95% confidence interval, 0.72-0.97), CTG-FBS (RR, 0.71; 95% CI, 0.63-0.80), CTG-lactate (RR, 0.77; 95% CI, 0.64-0.92), and FPO-CTG-FBS (RR, 0.81; 95% CI, 0.67-0.99). Conversely, compared with IA, STAN-CTG-FBS and cCTG-FBS raised risk of emergency cesarean deliveries by 17% and 21%, respectively.

Compared with other modalities, the superiority of intermittent auscultation was even more pronounced in terms of emergency cesarean deliveries because of fetal distress. Intermittent auscultation reduced risk by 43%, compared with CTG, 66% compared with CTG-FBS, 58%, compared with FPO-CTG, and 17%, compared with FPO-CTG-FBS. Conversely, compared with intermittent auscultation, STAN-CTG and cCTG-FBS increased risk of emergency cesarean deliveries because of fetal distress by 39% and 80%, respectively.

Further analysis showed that all types of surveillance had similar effects on neonatal outcomes, such as admission to neonatal unit and neonatal acidemia. Although a combination of STAN or FPO with CTG-FBS “seemed to improve the likelihood of reducing adverse neonatal outcomes,” the investigators noted that these differences were not significant in network meta­-analysis.

“New fetal surveillance methods did not improve neonatal outcomes or reduce unnecessary maternal interventions,” Dr. Al Wattar and colleagues concluded. “Further evidence is needed to evaluate the effects of fetal pulse oximetry and fetal heart electrocardiography in labor.”

Courtney Rhoades, DO, MBA, FACOG, medical director of labor and delivery and assistant professor of obstetrics and gynecology at the University of Florida, Jacksonville, suggested that the meta-analysis supports the safety of intermittent auscultation, but the results may not be entirely applicable to real-world practice.

“It is hard, in practice, to draw the same conclusion that they do in the study that the newer methods may cause too many emergency C-sections because our fetal monitoring equipment, methodology for interpretation, ability to do emergency C-sections and maternal risk factors have changed in the last 50 years,” Dr. Rhoades said. “Continuous fetal monitoring gives more data points during labor, and with more data points, there are more opportunities to interpret and act – either correctly or incorrectly. As they state in the study, the decision to do a C-section is multifactorial.”

Dr. Rhoades, who recently authored a textbook chapter on intrapartum monitoring and fetal assessment, recommended that intermittent auscultation be reserved for low-risk patients.

“The American College of Obstetricians and Gynecologists has endorsed intermittent auscultation for low-risk pregnancies and this study affirms their support,” Dr. Rhoades said. “Women with a low-risk pregnancy can benefit from intermittent auscultation because it allows them more autonomy and movement during labor so it should be offered to our low-risk patients.”

Dr. Al Wattar reported a personal Academic Clinical Lectureship from the U.K. National Health Institute of Research. Dr. Khan disclosed funding from the Beatriz Galindo Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

Spring 2021 has arrived with summer quickly approaching. It is our second spring and summer during the pandemic. Travel restrictions have minimally eased for vaccinated adults. However, neither domestic nor international leisure travel is encouraged for anyone. Ironically, air travel is increasing. For many families, it is time to make decisions regarding summer activities. Outdoor activities have been encouraged throughout the pandemic, which makes it a good time to review tick-borne diseases. Depending on your location, your patients may only have to travel as far as their backyard to sustain a tick bite.

Ticks are a group of obligate, bloodsucking arthropods that feed on mammals, birds, and reptiles. There are three families of ticks. Two families, Ixodidae (hard-bodied ticks) and Argasidae (soft-bodied ticks) are responsible for transmitting the most diseases to humans in the United States. Once a tick is infected with a pathogen it usually survives and transmits it to its next host. Ticks efficiently transmit bacteria, spirochetes, protozoa, rickettsiae, nematodes, and toxins to humans during feeding when the site is exposed to infected salivary gland secretions or regurgitated midgut contents. Pathogen transmission can also occur when the feeding site is contaminated by feces or coxal fluid. Sometimes a tick can transmit multiple pathogens. Not all pathogens are infectious (e.g., tick paralysis, which occurs after exposure to a neurotoxin and red meat allergy because of alpha-gal). Ticks require a blood meal to transform to their next stage of development (larva to nymph to adult). Life cycles of hard and soft ticks differ with most hard ticks undergoing a 2-year life cycle and feeding slowly over many days. In contrast, soft ticks feed multiple times often for less than 1 hour and are capable of transmitting diseases in less than 1 minute.

Rocky Mountain spotted fever was the first recognized tick-borne disease (TBD) in humans. Since then, 18 additional pathogens transmitted by ticks have been identified with 40% being described since 1980. The increased discovery of tickborne pathogens has been attributed to physician awareness of TBD and improved diagnostics. The number of cases of TBD has risen yearly. Ticks are responsible for most vector-transmitted diseases in the United States with Lyme disease most frequently reported.

Mosquito transmission accounts for only 7% of vector-borne diseases. Three species of ticks are responsible for most human disease: Ixodes scapularis (Black-legged tick), Amblyomma americanum (Lone Star tick), and Dermacentor variabilis (American dog tick). Each is capable of transmitting agents that cause multiple diseases.

Risk for acquisition of a specific disease is dependent upon the type of tick, its geographic location, the season, and duration of the exposure.

Humans are usually incidental hosts. Tick exposure can occur year-round, but tick activity is greatest between April and September. Ticks are generally found near the ground, in brushy or wooded areas. They can climb tall grasses or shrubs and wait for a potential host to brush against them. When this occurs, they seek a site for attachment.

In the absence of a vaccine, prevention of TBD is totally dependent upon your patients/parents understanding of when and where they are at risk for exposure and for us as physicians to know which pathogens can potentially be transmitted by ticks. Data regarding potential exposure risks are based on where a TBD was diagnosed, not necessarily where it was acquired. National maps that illustrate the distribution of medically significant ticks and presence or prevalence of tick-borne pathogens in specific areas within a region previously may have been incomplete or outdated. The Centers for Disease Control and Prevention initiated a national tick surveillance program in 2017; five universities were established as regional centers of excellence to help prevent and rapidly respond to emerging vector-borne diseases across the United States. One goal is to standardize tick surveillance activities at the state level. For state-specific activity go to https://www.cdc.gov/ncezid/dvbd/vital-signs/index.html.
 

Prevention: Here are a few environmental interventions you can recommend to your patients

• Remove leaf litter, clear tall brush, and grass around the home and at edge of lawns. Mow the lawn frequently.
• Keep playground equipment, decks, and patios away from yard edges and trees.
• Live near a wooded area? Place a 3-ft.-wide barrier of gravel or wood chips between the areas.
• Put up a fence to keep unwanted animals out.
• Keep the yard free of potential hiding place for ticks (e.g., mattresses or furniture).
• Stack wood neatly and in a dry area.
• Use pesticides, but do not rely on them solely to prevent ticks exposure.

Personal interventions for patients when outdoors

• Use Environmental Protection Agency–registered insect repellents. Note: Oil of lemon-, eucalyptus-, and para-menthane-diol–containing products should not be used in children aged3 years or less.
• Treat clothing and gear with products containing 0.5% permethrin to repel mosquitoes and ticks.
• Check cloths for ticks. Drying clothes on high heat for 10 minutes will kill ticks. If washing is needed use hot water. Lower temperatures will not kill ticks.
• Do daily body checks for ticks after coming indoors.
• Check pets for ticks.

Tick removal

• Take tweezers, grasp the tick as close to the skin’s surface as possible.
• Pull upward. Do not twist or jerk the tick. Place in a container. Ideally submit for species identification.
• After removal, clean the bite area with alcohol or soap and water.
• Never crush a tick with your fingers.

When should you include TBD in your differential for a sick child?

Headache, fever, arthralgia, and rash are symptoms for several infectious diseases. Obtaining a history of recent activities, tick bite, or travel to areas where these diseases are more prevalent is important. You must have a high index of suspicion. Clinical and laboratory clues may help.

Delay in treatment is more detrimental. If you suspect rickettsia, ehrlichiosis, or anaplasmosis, doxycycline should be started promptly regardless of age. Consultation with an infectious disease specialist is recommended.

The United States recognizes it is not adequately prepared to address the continuing rise of vector-borne diseases. In response, on Jan. 20, 2021, the CDC’s division of vector-borne diseases with input from five federal departments and the EPA developed a joint National Public Health Framework for the Prevention and Control of Vector-Borne Diseases in Humans to tackle issues including risk, detection, diagnosis, treatment, prevention and control of TBD. Stay tuned.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

Spring 2021 has arrived with summer quickly approaching. It is our second spring and summer during the pandemic. Travel restrictions have minimally eased for vaccinated adults. However, neither domestic nor international leisure travel is encouraged for anyone. Ironically, air travel is increasing. For many families, it is time to make decisions regarding summer activities. Outdoor activities have been encouraged throughout the pandemic, which makes it a good time to review tick-borne diseases. Depending on your location, your patients may only have to travel as far as their backyard to sustain a tick bite.

Ticks are a group of obligate, bloodsucking arthropods that feed on mammals, birds, and reptiles. There are three families of ticks. Two families, Ixodidae (hard-bodied ticks) and Argasidae (soft-bodied ticks) are responsible for transmitting the most diseases to humans in the United States. Once a tick is infected with a pathogen it usually survives and transmits it to its next host. Ticks efficiently transmit bacteria, spirochetes, protozoa, rickettsiae, nematodes, and toxins to humans during feeding when the site is exposed to infected salivary gland secretions or regurgitated midgut contents. Pathogen transmission can also occur when the feeding site is contaminated by feces or coxal fluid. Sometimes a tick can transmit multiple pathogens. Not all pathogens are infectious (e.g., tick paralysis, which occurs after exposure to a neurotoxin and red meat allergy because of alpha-gal). Ticks require a blood meal to transform to their next stage of development (larva to nymph to adult). Life cycles of hard and soft ticks differ with most hard ticks undergoing a 2-year life cycle and feeding slowly over many days. In contrast, soft ticks feed multiple times often for less than 1 hour and are capable of transmitting diseases in less than 1 minute.

Rocky Mountain spotted fever was the first recognized tick-borne disease (TBD) in humans. Since then, 18 additional pathogens transmitted by ticks have been identified with 40% being described since 1980. The increased discovery of tickborne pathogens has been attributed to physician awareness of TBD and improved diagnostics. The number of cases of TBD has risen yearly. Ticks are responsible for most vector-transmitted diseases in the United States with Lyme disease most frequently reported.

Mosquito transmission accounts for only 7% of vector-borne diseases. Three species of ticks are responsible for most human disease: Ixodes scapularis (Black-legged tick), Amblyomma americanum (Lone Star tick), and Dermacentor variabilis (American dog tick). Each is capable of transmitting agents that cause multiple diseases.

Risk for acquisition of a specific disease is dependent upon the type of tick, its geographic location, the season, and duration of the exposure.

Humans are usually incidental hosts. Tick exposure can occur year-round, but tick activity is greatest between April and September. Ticks are generally found near the ground, in brushy or wooded areas. They can climb tall grasses or shrubs and wait for a potential host to brush against them. When this occurs, they seek a site for attachment.

In the absence of a vaccine, prevention of TBD is totally dependent upon your patients/parents understanding of when and where they are at risk for exposure and for us as physicians to know which pathogens can potentially be transmitted by ticks. Data regarding potential exposure risks are based on where a TBD was diagnosed, not necessarily where it was acquired. National maps that illustrate the distribution of medically significant ticks and presence or prevalence of tick-borne pathogens in specific areas within a region previously may have been incomplete or outdated. The Centers for Disease Control and Prevention initiated a national tick surveillance program in 2017; five universities were established as regional centers of excellence to help prevent and rapidly respond to emerging vector-borne diseases across the United States. One goal is to standardize tick surveillance activities at the state level. For state-specific activity go to https://www.cdc.gov/ncezid/dvbd/vital-signs/index.html.
 

Prevention: Here are a few environmental interventions you can recommend to your patients

• Remove leaf litter, clear tall brush, and grass around the home and at edge of lawns. Mow the lawn frequently.
• Keep playground equipment, decks, and patios away from yard edges and trees.
• Live near a wooded area? Place a 3-ft.-wide barrier of gravel or wood chips between the areas.
• Put up a fence to keep unwanted animals out.
• Keep the yard free of potential hiding place for ticks (e.g., mattresses or furniture).
• Stack wood neatly and in a dry area.
• Use pesticides, but do not rely on them solely to prevent ticks exposure.

Personal interventions for patients when outdoors

• Use Environmental Protection Agency–registered insect repellents. Note: Oil of lemon-, eucalyptus-, and para-menthane-diol–containing products should not be used in children aged3 years or less.
• Treat clothing and gear with products containing 0.5% permethrin to repel mosquitoes and ticks.
• Check cloths for ticks. Drying clothes on high heat for 10 minutes will kill ticks. If washing is needed use hot water. Lower temperatures will not kill ticks.
• Do daily body checks for ticks after coming indoors.
• Check pets for ticks.

Tick removal

• Take tweezers, grasp the tick as close to the skin’s surface as possible.
• Pull upward. Do not twist or jerk the tick. Place in a container. Ideally submit for species identification.
• After removal, clean the bite area with alcohol or soap and water.
• Never crush a tick with your fingers.

When should you include TBD in your differential for a sick child?

Headache, fever, arthralgia, and rash are symptoms for several infectious diseases. Obtaining a history of recent activities, tick bite, or travel to areas where these diseases are more prevalent is important. You must have a high index of suspicion. Clinical and laboratory clues may help.

Delay in treatment is more detrimental. If you suspect rickettsia, ehrlichiosis, or anaplasmosis, doxycycline should be started promptly regardless of age. Consultation with an infectious disease specialist is recommended.

The United States recognizes it is not adequately prepared to address the continuing rise of vector-borne diseases. In response, on Jan. 20, 2021, the CDC’s division of vector-borne diseases with input from five federal departments and the EPA developed a joint National Public Health Framework for the Prevention and Control of Vector-Borne Diseases in Humans to tackle issues including risk, detection, diagnosis, treatment, prevention and control of TBD. Stay tuned.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

Spring 2021 has arrived with summer quickly approaching. It is our second spring and summer during the pandemic. Travel restrictions have minimally eased for vaccinated adults. However, neither domestic nor international leisure travel is encouraged for anyone. Ironically, air travel is increasing. For many families, it is time to make decisions regarding summer activities. Outdoor activities have been encouraged throughout the pandemic, which makes it a good time to review tick-borne diseases. Depending on your location, your patients may only have to travel as far as their backyard to sustain a tick bite.

Ticks are a group of obligate, bloodsucking arthropods that feed on mammals, birds, and reptiles. There are three families of ticks. Two families, Ixodidae (hard-bodied ticks) and Argasidae (soft-bodied ticks) are responsible for transmitting the most diseases to humans in the United States. Once a tick is infected with a pathogen it usually survives and transmits it to its next host. Ticks efficiently transmit bacteria, spirochetes, protozoa, rickettsiae, nematodes, and toxins to humans during feeding when the site is exposed to infected salivary gland secretions or regurgitated midgut contents. Pathogen transmission can also occur when the feeding site is contaminated by feces or coxal fluid. Sometimes a tick can transmit multiple pathogens. Not all pathogens are infectious (e.g., tick paralysis, which occurs after exposure to a neurotoxin and red meat allergy because of alpha-gal). Ticks require a blood meal to transform to their next stage of development (larva to nymph to adult). Life cycles of hard and soft ticks differ with most hard ticks undergoing a 2-year life cycle and feeding slowly over many days. In contrast, soft ticks feed multiple times often for less than 1 hour and are capable of transmitting diseases in less than 1 minute.

Rocky Mountain spotted fever was the first recognized tick-borne disease (TBD) in humans. Since then, 18 additional pathogens transmitted by ticks have been identified with 40% being described since 1980. The increased discovery of tickborne pathogens has been attributed to physician awareness of TBD and improved diagnostics. The number of cases of TBD has risen yearly. Ticks are responsible for most vector-transmitted diseases in the United States with Lyme disease most frequently reported.

Mosquito transmission accounts for only 7% of vector-borne diseases. Three species of ticks are responsible for most human disease: Ixodes scapularis (Black-legged tick), Amblyomma americanum (Lone Star tick), and Dermacentor variabilis (American dog tick). Each is capable of transmitting agents that cause multiple diseases.

Risk for acquisition of a specific disease is dependent upon the type of tick, its geographic location, the season, and duration of the exposure.

Humans are usually incidental hosts. Tick exposure can occur year-round, but tick activity is greatest between April and September. Ticks are generally found near the ground, in brushy or wooded areas. They can climb tall grasses or shrubs and wait for a potential host to brush against them. When this occurs, they seek a site for attachment.

In the absence of a vaccine, prevention of TBD is totally dependent upon your patients/parents understanding of when and where they are at risk for exposure and for us as physicians to know which pathogens can potentially be transmitted by ticks. Data regarding potential exposure risks are based on where a TBD was diagnosed, not necessarily where it was acquired. National maps that illustrate the distribution of medically significant ticks and presence or prevalence of tick-borne pathogens in specific areas within a region previously may have been incomplete or outdated. The Centers for Disease Control and Prevention initiated a national tick surveillance program in 2017; five universities were established as regional centers of excellence to help prevent and rapidly respond to emerging vector-borne diseases across the United States. One goal is to standardize tick surveillance activities at the state level. For state-specific activity go to https://www.cdc.gov/ncezid/dvbd/vital-signs/index.html.
 

Prevention: Here are a few environmental interventions you can recommend to your patients

• Remove leaf litter, clear tall brush, and grass around the home and at edge of lawns. Mow the lawn frequently.
• Keep playground equipment, decks, and patios away from yard edges and trees.
• Live near a wooded area? Place a 3-ft.-wide barrier of gravel or wood chips between the areas.
• Put up a fence to keep unwanted animals out.
• Keep the yard free of potential hiding place for ticks (e.g., mattresses or furniture).
• Stack wood neatly and in a dry area.
• Use pesticides, but do not rely on them solely to prevent ticks exposure.

Personal interventions for patients when outdoors

• Use Environmental Protection Agency–registered insect repellents. Note: Oil of lemon-, eucalyptus-, and para-menthane-diol–containing products should not be used in children aged3 years or less.
• Treat clothing and gear with products containing 0.5% permethrin to repel mosquitoes and ticks.
• Check cloths for ticks. Drying clothes on high heat for 10 minutes will kill ticks. If washing is needed use hot water. Lower temperatures will not kill ticks.
• Do daily body checks for ticks after coming indoors.
• Check pets for ticks.

Tick removal

• Take tweezers, grasp the tick as close to the skin’s surface as possible.
• Pull upward. Do not twist or jerk the tick. Place in a container. Ideally submit for species identification.
• After removal, clean the bite area with alcohol or soap and water.
• Never crush a tick with your fingers.

When should you include TBD in your differential for a sick child?

Headache, fever, arthralgia, and rash are symptoms for several infectious diseases. Obtaining a history of recent activities, tick bite, or travel to areas where these diseases are more prevalent is important. You must have a high index of suspicion. Clinical and laboratory clues may help.

Delay in treatment is more detrimental. If you suspect rickettsia, ehrlichiosis, or anaplasmosis, doxycycline should be started promptly regardless of age. Consultation with an infectious disease specialist is recommended.

The United States recognizes it is not adequately prepared to address the continuing rise of vector-borne diseases. In response, on Jan. 20, 2021, the CDC’s division of vector-borne diseases with input from five federal departments and the EPA developed a joint National Public Health Framework for the Prevention and Control of Vector-Borne Diseases in Humans to tackle issues including risk, detection, diagnosis, treatment, prevention and control of TBD. Stay tuned.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

During the past year, adolescents, families, educators, and health care providers have had to press forward through myriad challenges and stressors with flexibility and adaptability. With appropriate concern, we ask ourselves how children and youth are coping emotionally with the unprecedented changes of the past year.

Adolescent substance use represents an important area of concern. What has happened during the pandemic? Has youth substance use increased or decreased? Has access to substances increased or decreased, has monitoring and support for at-risk youth increased or decreased?

The answers to these questions are mixed. If anything, the pandemic has highlighted the heterogeneity of adolescent substance use. Now is a key time for assessment, support, and conversation with teens and families.

Monitoring the Future (MTF), a nationally representative annual survey, has provided a broad perspective on trends of adolescent substance use for decades.¹ The MTF data is usually collected from February to May and was cut short in 2020 because of school closures associated with the pandemic. The sample size, though still nationally representative, was about a quarter of the typical volume. Some of the data are encouraging, including a flattening out of previous years’ stark increase in vaping of both nicotine and cannabis products (though overall numbers remain alarmingly high). Other data are more concerning including a continued increase in misuse of cough medicine, amphetamines, and inhalants among the youngest cohort surveyed (eighth graders). However, these data were largely representative of prepandemic circumstances.

The COVID-19 pandemic has significantly affected risk and protective factors for teen drug and alcohol use. Most notably, it has had a widely observed negative impact on adolescent mental health, across multiple disease categories.² In addition, the cancellation of in-person academic and extracurricular activities such as arts and athletics markedly increased unstructured time, a known associated factor for higher-risk activities including substance use. This has also led to decreased contact with many supportive adults such as teachers and coaches. On the other hand, some adolescents now have more time with supportive parents and caregivers, more meals together, and more supervision, all of which are associated with decreased likelihood of substance use disorders.

The highly variable reasons for substance use affect highly variable pandemic-related changes in use. Understanding the impetus for use is a good place to start conversation and can help providers assess risk of escalation during the pandemic. Some teens primarily use for social enhancement while others use as a means of coping with stress or to mask or escape negative emotions. Still others continue use because of physiological dependence, craving, and other symptoms consistent with use disorders.

Highlighting the heterogeneity of this issue, one study assessing use early in the pandemic showed a decrease in the percentage of teens who use substances but an increase in frequency of use for those who are using.³ Though expected, an increase in frequency of use by oneself as compared with peers was also notable. Using substances alone is associated with more severe use disorders, carries greater risk of overdose, and can increase shame and secrecy, further fueling use disorders.

The pandemic has thus represented a protective pause for some experimental or socially motivated substance-using teens who have experienced a period of abstinence even if not fully by choice. For others, it has represented an acute amplification of risk factors and use has accelerated. This latter group includes those whose use represents an effort to cope with depression, anxiety, and loneliness or for whom isolation at home represents less monitoring, increased access, and greater exposure to substances.

Over the past year, in the treatment of adolescents struggling with substance use, many clinicians have observed a sifting effect during these unprecedented social changes. Many youth, who no longer have access to substances, have found they can “take it or leave it”. Other youth have been observed engaging in additional risk or going to greater lengths to access substances and continue their use. For both groups and everyone in between, this is an important time for screening, clinical assessment, and support.

While anticipating further research and data regarding broad substance use trends, including MTF data from 2021, recognizing that the impact of the COVID-19 pandemic is individual, with marked differences from adolescent to adolescent, will help us continue to act now to assess this important area of adolescent health. The first step for primary care providers is unchanged: to routinely screen for and discuss substance use in clinical settings.

Two brief, validated, easily accessible screening tools are available for primary care settings. They can both be self-administered and take less than 2 minutes to complete. Screening, Brief Intervention and Referral to Treatment and the Brief Screener for Tobacco, Alcohol and other Drugs can both be used for youth aged 12-17 years.^4,5 Both screens are available online at drugabuse.gov.⁶

Routine screening will normalize conversations about substance use and healthy choices, provide opportunities for positive reinforcement, identify adolescents at risk, increase comfort and competence in providing brief intervention, and expedite referrals for additional support and treatment.

A false assumption that a particular adolescent isn’t using substances creates a missed opportunity to offer guidance and treatment. An oft-overlooked opportunity is that of providing positive reinforcement for an adolescent who isn’t using any substances or experimenting at all. Positive reinforcement is a strong component of reinforcing health maintenance.

Parent guidance and family assessment will also be critical tools. Parents and caregivers play a primary role in substance use treatment for teens and have a contributory impact on risk through both genes and environment. Of note, research suggests a moderate overall increase in adult substance use during the pandemic, particularly substances that are widely available such as alcohol. Adolescents may thus have greater access and exposure to substance use. A remarkably high percentage, 42%, of substance-using teens surveyed early in the pandemic indicated that they were using substances with their parents.³ Parents, who have equally been challenged by the pandemic, may need guidance in balancing compassion and support for struggling youth, while setting appropriate limits and maintaining expectations of healthy activities.

Unprecedented change and uncertainty provide an opportunity to reassess risks and openly discuss substance use with youth and families. Even with much on our minds during the COVID-19 pandemic, we can maintain focus on this significant risk to adolescent health and wellness. Our efforts now, from screening to treatment for adolescent substance use should be reinforced rather than delayed.

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington.

References

1. Monitoringthefuture.org

2. Jones EAK et al. Int J Environ Res Public Health, 2021;18(5):2470.

3. Dumas TM et al. J Adolesc Health, 2020;67(3):354-61.

4. Levy S et al. JAMA Pediatr. 2014;168(9):822-8.

5. Kelly SM et al. Pediatrics. 2014;133(5):819-26.

6. National Institute on Drug Abuse. Adolescent Substance Use Screening Tools. 2016 Apr 27. https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-prevention/screening-tools-adolescent-substance-use/adolescent-substance-use-screening-tools

During the past year, adolescents, families, educators, and health care providers have had to press forward through myriad challenges and stressors with flexibility and adaptability. With appropriate concern, we ask ourselves how children and youth are coping emotionally with the unprecedented changes of the past year.

Adolescent substance use represents an important area of concern. What has happened during the pandemic? Has youth substance use increased or decreased? Has access to substances increased or decreased, has monitoring and support for at-risk youth increased or decreased?

The answers to these questions are mixed. If anything, the pandemic has highlighted the heterogeneity of adolescent substance use. Now is a key time for assessment, support, and conversation with teens and families.

Monitoring the Future (MTF), a nationally representative annual survey, has provided a broad perspective on trends of adolescent substance use for decades.¹ The MTF data is usually collected from February to May and was cut short in 2020 because of school closures associated with the pandemic. The sample size, though still nationally representative, was about a quarter of the typical volume. Some of the data are encouraging, including a flattening out of previous years’ stark increase in vaping of both nicotine and cannabis products (though overall numbers remain alarmingly high). Other data are more concerning including a continued increase in misuse of cough medicine, amphetamines, and inhalants among the youngest cohort surveyed (eighth graders). However, these data were largely representative of prepandemic circumstances.

The COVID-19 pandemic has significantly affected risk and protective factors for teen drug and alcohol use. Most notably, it has had a widely observed negative impact on adolescent mental health, across multiple disease categories.² In addition, the cancellation of in-person academic and extracurricular activities such as arts and athletics markedly increased unstructured time, a known associated factor for higher-risk activities including substance use. This has also led to decreased contact with many supportive adults such as teachers and coaches. On the other hand, some adolescents now have more time with supportive parents and caregivers, more meals together, and more supervision, all of which are associated with decreased likelihood of substance use disorders.

The highly variable reasons for substance use affect highly variable pandemic-related changes in use. Understanding the impetus for use is a good place to start conversation and can help providers assess risk of escalation during the pandemic. Some teens primarily use for social enhancement while others use as a means of coping with stress or to mask or escape negative emotions. Still others continue use because of physiological dependence, craving, and other symptoms consistent with use disorders.

Highlighting the heterogeneity of this issue, one study assessing use early in the pandemic showed a decrease in the percentage of teens who use substances but an increase in frequency of use for those who are using.³ Though expected, an increase in frequency of use by oneself as compared with peers was also notable. Using substances alone is associated with more severe use disorders, carries greater risk of overdose, and can increase shame and secrecy, further fueling use disorders.

The pandemic has thus represented a protective pause for some experimental or socially motivated substance-using teens who have experienced a period of abstinence even if not fully by choice. For others, it has represented an acute amplification of risk factors and use has accelerated. This latter group includes those whose use represents an effort to cope with depression, anxiety, and loneliness or for whom isolation at home represents less monitoring, increased access, and greater exposure to substances.

Over the past year, in the treatment of adolescents struggling with substance use, many clinicians have observed a sifting effect during these unprecedented social changes. Many youth, who no longer have access to substances, have found they can “take it or leave it”. Other youth have been observed engaging in additional risk or going to greater lengths to access substances and continue their use. For both groups and everyone in between, this is an important time for screening, clinical assessment, and support.

While anticipating further research and data regarding broad substance use trends, including MTF data from 2021, recognizing that the impact of the COVID-19 pandemic is individual, with marked differences from adolescent to adolescent, will help us continue to act now to assess this important area of adolescent health. The first step for primary care providers is unchanged: to routinely screen for and discuss substance use in clinical settings.

Two brief, validated, easily accessible screening tools are available for primary care settings. They can both be self-administered and take less than 2 minutes to complete. Screening, Brief Intervention and Referral to Treatment and the Brief Screener for Tobacco, Alcohol and other Drugs can both be used for youth aged 12-17 years.^4,5 Both screens are available online at drugabuse.gov.⁶

Routine screening will normalize conversations about substance use and healthy choices, provide opportunities for positive reinforcement, identify adolescents at risk, increase comfort and competence in providing brief intervention, and expedite referrals for additional support and treatment.

A false assumption that a particular adolescent isn’t using substances creates a missed opportunity to offer guidance and treatment. An oft-overlooked opportunity is that of providing positive reinforcement for an adolescent who isn’t using any substances or experimenting at all. Positive reinforcement is a strong component of reinforcing health maintenance.

Parent guidance and family assessment will also be critical tools. Parents and caregivers play a primary role in substance use treatment for teens and have a contributory impact on risk through both genes and environment. Of note, research suggests a moderate overall increase in adult substance use during the pandemic, particularly substances that are widely available such as alcohol. Adolescents may thus have greater access and exposure to substance use. A remarkably high percentage, 42%, of substance-using teens surveyed early in the pandemic indicated that they were using substances with their parents.³ Parents, who have equally been challenged by the pandemic, may need guidance in balancing compassion and support for struggling youth, while setting appropriate limits and maintaining expectations of healthy activities.

Unprecedented change and uncertainty provide an opportunity to reassess risks and openly discuss substance use with youth and families. Even with much on our minds during the COVID-19 pandemic, we can maintain focus on this significant risk to adolescent health and wellness. Our efforts now, from screening to treatment for adolescent substance use should be reinforced rather than delayed.

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington.

References

1. Monitoringthefuture.org

2. Jones EAK et al. Int J Environ Res Public Health, 2021;18(5):2470.

3. Dumas TM et al. J Adolesc Health, 2020;67(3):354-61.

4. Levy S et al. JAMA Pediatr. 2014;168(9):822-8.

5. Kelly SM et al. Pediatrics. 2014;133(5):819-26.

6. National Institute on Drug Abuse. Adolescent Substance Use Screening Tools. 2016 Apr 27. https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-prevention/screening-tools-adolescent-substance-use/adolescent-substance-use-screening-tools

During the past year, adolescents, families, educators, and health care providers have had to press forward through myriad challenges and stressors with flexibility and adaptability. With appropriate concern, we ask ourselves how children and youth are coping emotionally with the unprecedented changes of the past year.

Adolescent substance use represents an important area of concern. What has happened during the pandemic? Has youth substance use increased or decreased? Has access to substances increased or decreased, has monitoring and support for at-risk youth increased or decreased?

The answers to these questions are mixed. If anything, the pandemic has highlighted the heterogeneity of adolescent substance use. Now is a key time for assessment, support, and conversation with teens and families.

Monitoring the Future (MTF), a nationally representative annual survey, has provided a broad perspective on trends of adolescent substance use for decades.¹ The MTF data is usually collected from February to May and was cut short in 2020 because of school closures associated with the pandemic. The sample size, though still nationally representative, was about a quarter of the typical volume. Some of the data are encouraging, including a flattening out of previous years’ stark increase in vaping of both nicotine and cannabis products (though overall numbers remain alarmingly high). Other data are more concerning including a continued increase in misuse of cough medicine, amphetamines, and inhalants among the youngest cohort surveyed (eighth graders). However, these data were largely representative of prepandemic circumstances.

The COVID-19 pandemic has significantly affected risk and protective factors for teen drug and alcohol use. Most notably, it has had a widely observed negative impact on adolescent mental health, across multiple disease categories.² In addition, the cancellation of in-person academic and extracurricular activities such as arts and athletics markedly increased unstructured time, a known associated factor for higher-risk activities including substance use. This has also led to decreased contact with many supportive adults such as teachers and coaches. On the other hand, some adolescents now have more time with supportive parents and caregivers, more meals together, and more supervision, all of which are associated with decreased likelihood of substance use disorders.

The highly variable reasons for substance use affect highly variable pandemic-related changes in use. Understanding the impetus for use is a good place to start conversation and can help providers assess risk of escalation during the pandemic. Some teens primarily use for social enhancement while others use as a means of coping with stress or to mask or escape negative emotions. Still others continue use because of physiological dependence, craving, and other symptoms consistent with use disorders.

Highlighting the heterogeneity of this issue, one study assessing use early in the pandemic showed a decrease in the percentage of teens who use substances but an increase in frequency of use for those who are using.³ Though expected, an increase in frequency of use by oneself as compared with peers was also notable. Using substances alone is associated with more severe use disorders, carries greater risk of overdose, and can increase shame and secrecy, further fueling use disorders.

The pandemic has thus represented a protective pause for some experimental or socially motivated substance-using teens who have experienced a period of abstinence even if not fully by choice. For others, it has represented an acute amplification of risk factors and use has accelerated. This latter group includes those whose use represents an effort to cope with depression, anxiety, and loneliness or for whom isolation at home represents less monitoring, increased access, and greater exposure to substances.

Over the past year, in the treatment of adolescents struggling with substance use, many clinicians have observed a sifting effect during these unprecedented social changes. Many youth, who no longer have access to substances, have found they can “take it or leave it”. Other youth have been observed engaging in additional risk or going to greater lengths to access substances and continue their use. For both groups and everyone in between, this is an important time for screening, clinical assessment, and support.

While anticipating further research and data regarding broad substance use trends, including MTF data from 2021, recognizing that the impact of the COVID-19 pandemic is individual, with marked differences from adolescent to adolescent, will help us continue to act now to assess this important area of adolescent health. The first step for primary care providers is unchanged: to routinely screen for and discuss substance use in clinical settings.

Two brief, validated, easily accessible screening tools are available for primary care settings. They can both be self-administered and take less than 2 minutes to complete. Screening, Brief Intervention and Referral to Treatment and the Brief Screener for Tobacco, Alcohol and other Drugs can both be used for youth aged 12-17 years.^4,5 Both screens are available online at drugabuse.gov.⁶

Routine screening will normalize conversations about substance use and healthy choices, provide opportunities for positive reinforcement, identify adolescents at risk, increase comfort and competence in providing brief intervention, and expedite referrals for additional support and treatment.

A false assumption that a particular adolescent isn’t using substances creates a missed opportunity to offer guidance and treatment. An oft-overlooked opportunity is that of providing positive reinforcement for an adolescent who isn’t using any substances or experimenting at all. Positive reinforcement is a strong component of reinforcing health maintenance.

Parent guidance and family assessment will also be critical tools. Parents and caregivers play a primary role in substance use treatment for teens and have a contributory impact on risk through both genes and environment. Of note, research suggests a moderate overall increase in adult substance use during the pandemic, particularly substances that are widely available such as alcohol. Adolescents may thus have greater access and exposure to substance use. A remarkably high percentage, 42%, of substance-using teens surveyed early in the pandemic indicated that they were using substances with their parents.³ Parents, who have equally been challenged by the pandemic, may need guidance in balancing compassion and support for struggling youth, while setting appropriate limits and maintaining expectations of healthy activities.

Unprecedented change and uncertainty provide an opportunity to reassess risks and openly discuss substance use with youth and families. Even with much on our minds during the COVID-19 pandemic, we can maintain focus on this significant risk to adolescent health and wellness. Our efforts now, from screening to treatment for adolescent substance use should be reinforced rather than delayed.

Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington.

References

1. Monitoringthefuture.org

2. Jones EAK et al. Int J Environ Res Public Health, 2021;18(5):2470.

3. Dumas TM et al. J Adolesc Health, 2020;67(3):354-61.

4. Levy S et al. JAMA Pediatr. 2014;168(9):822-8.

5. Kelly SM et al. Pediatrics. 2014;133(5):819-26.

6. National Institute on Drug Abuse. Adolescent Substance Use Screening Tools. 2016 Apr 27. https://www.drugabuse.gov/nidamed-medical-health-professionals/screening-tools-prevention/screening-tools-adolescent-substance-use/adolescent-substance-use-screening-tools

You read “thoughts of being better off dead” on your next patient’s PHQ-9 screen results and break into a sweat. After eliciting the teen’s realistic suicide plan and intent you send him to the ED with his parent for crisis mental health evaluation. When you call the family that evening to follow-up you hear that he was discharged with a “mental health counseling” appointment next week.

Have you done enough to prevent this child from dying at his own hand? I imagine that this haunts you as it does me. It is terrifying to know that, of youth with suicidal ideation, over one-third attempt suicide, most within 1-2 years, and 20%-40% do so without having had a plan.

We now know that certain kinds of psychotherapy have evidence for preventing subsequent suicide in teens at high risk due to suicidal ideation and past attempts. Cognitive behavioral therapy (CBT) has the best evidence including its subtypes for youth with relevant histories: for both suicide and substance use (integrated, or I-CBT), trauma focused (TF-CBT), traumatic grief (CTG-CBT), and CBT-I, for the potent risk factor of insomnia. The other treatment shown to reduce risk is dialectical behavioral therapy–adolescent (DBT-A) focused on strengthening skills in interpersonal effectiveness, mindfulness, distress tolerance, and emotion regulation adapted to youth by adding family therapy and multifamily skills training. Interpersonal psychotherapy (IPT) adapted for suicidal and self-harming adolescents (IPT-SA) also has evidence.

Some school programs have shown moderate efficacy, for example (IPT-A-IN) addresses the social and interpersonal context, and Youth Aware of Mental Health, a school curriculum to increase knowledge, help-seeking, and ways of coping with depression and suicidal behavior, that cut suicide attempts by half.

You may be able to recommend, refer to, or check to see if a youth can be provided one of the above therapies with best evidence but getting any counseling at all can be hard and some, especially minority families may decline formal interventions. Any therapy – CBT, DBT, or IPT – acceptable to the youth and family can be helpful. You can often determine if the key components are being provided by asking the teen what they are working on in therapy.

It is clear that checking in regularly with teens who have been through a suicide crisis is crucial to ensure that they continue in therapy long and consistently enough, that the family is involved in treatment, and that they are taught emotion regulation, distress tolerance, and safety planning. Warm, consistent parenting, good parent-child communication, and monitoring are protective factors but also skills that can be boosted to reduce future risk of suicide. When there is family dysfunction, conflict, or weak relationships, getting help for family relationships such as through attachment-based family therapy (ABFT) or family cognitive behavioral therapy is a priority. When bereavement or parental depression is contributing to youth suicidal thoughts, addressing these specifically can reduce suicide risk.

Sometimes family members, even with counseling, are not the best supporters for a teen in pain. When youths nominated their own support team to be informed about risk factors, diagnosis, and treatment plans and to stay in contact weekly there was a 6.6-fold lower risk of death than for nonsupported youth.

But how much of this evidence-based intervention can you ensure from your position in primary care? Refer if you can but regular supportive contacts alone reduce risk so you, trusted staff, school counselors, or even the now more available teletherapists may help. You can work with your patient to fill out a written commitment-to-safety plan (e.g. U. Colorado, CHADIS) of strategies they can use when having suicidal thoughts such as self-distractions, problem-solving, listing things they are looking forward to, things to do to get their mind off suicidal thoughts, and selecting support people to understand their situation with whom to be in regular contact. Any plan needs to take into account how understanding, supportive, and available the family is, factors you are most likely to be able to judge from your ongoing relationship, but that immediate risk may change. Contact within 48 hours, check-in within 1-2 weeks, and provision of crisis hotline information are essential actions.

Recommending home safety is part of routine anticipatory guidance but reduction of lethal means is essential in these cases. Guns are the most lethal method of suicide but discussing safe gun storage has been shown to be more effective than arguing in vain for gun removal. Medication overdose, a common means, can be reduced by not prescribing tricyclics (ineffective and more lethal), and advising parents to lock up all household medications.

You can ask about and coach teens on how to avoid the hazards of participating in online discussion groups, bullying, and cyberbullying (with risk for both perpetrator and victim), all risk factors for suicide. Managing insomnia can improve depression and is within your skills. While pediatricians can’t treat the suicide risk factors of family poverty, unemployment, or loss of culture/identity, we can refer affected families to community resources.

Repeated suicide screens can help but are imperfect, so listen to the child or parent for risk signs such as the youth having self-reported worthlessness, low self-esteem, speaking negatively about self, anhedonia, or poor emotion regulation. Children with impulsive aggression, often familial, are at special risk of suicide. This trait, while more common in ADHD, is not confined to that condition. You can help by optimizing medical management of impulsivity, when appropriate.

Most youth who attempt suicide have one or more mental health diagnoses, particularly major depressive disorder (MDD), eating disorder, ADHD, conduct, or intermittent explosive disorder. When MDD is comorbid with anxiety, suicides increase 9.5-fold. Children on the autism spectrum are more likely to have been bullied and eight times more likely to commit suicide. LGBTQ youth are five times more often bullied and are at high risk for suicide. The more common issues of school failure or substance use also confer risk. While we do our best caring for children with these conditions we may not be thinking about, screening, or monitoring for their suicide risk. It may be important for us to explain that, despite black-box warnings, rates of SSRI prescribing for depression are inversely related to suicides.

Child maltreatment is the highest risk factor for suicide (population attributed risk, or PAR, 9.6%-14.5%), particularly sexual misuse. All together, adverse childhood experiences have a PAR for suicide of 80%. Continuity allows you to monitor for developmental times when distress from past experiences often reemerges, e.g., puberty, dating onset, or divorce. Getting consent and sharing these highly sensitive but potentially triggering factors as well as prior diagnoses with a newly assigned therapist can be helpful to prioritize treatments to prevent a suicide attempt, because they may be difficult to elicit and timeliness is essential.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Brent DA. J Am Acad Child Adolesc Psychiatry. 2019;58(1):25-35.

Cha CB et al. J Child Psychol Psychiatry. 2018;59(4):460-82.

You read “thoughts of being better off dead” on your next patient’s PHQ-9 screen results and break into a sweat. After eliciting the teen’s realistic suicide plan and intent you send him to the ED with his parent for crisis mental health evaluation. When you call the family that evening to follow-up you hear that he was discharged with a “mental health counseling” appointment next week.

Have you done enough to prevent this child from dying at his own hand? I imagine that this haunts you as it does me. It is terrifying to know that, of youth with suicidal ideation, over one-third attempt suicide, most within 1-2 years, and 20%-40% do so without having had a plan.

We now know that certain kinds of psychotherapy have evidence for preventing subsequent suicide in teens at high risk due to suicidal ideation and past attempts. Cognitive behavioral therapy (CBT) has the best evidence including its subtypes for youth with relevant histories: for both suicide and substance use (integrated, or I-CBT), trauma focused (TF-CBT), traumatic grief (CTG-CBT), and CBT-I, for the potent risk factor of insomnia. The other treatment shown to reduce risk is dialectical behavioral therapy–adolescent (DBT-A) focused on strengthening skills in interpersonal effectiveness, mindfulness, distress tolerance, and emotion regulation adapted to youth by adding family therapy and multifamily skills training. Interpersonal psychotherapy (IPT) adapted for suicidal and self-harming adolescents (IPT-SA) also has evidence.

Some school programs have shown moderate efficacy, for example (IPT-A-IN) addresses the social and interpersonal context, and Youth Aware of Mental Health, a school curriculum to increase knowledge, help-seeking, and ways of coping with depression and suicidal behavior, that cut suicide attempts by half.

You may be able to recommend, refer to, or check to see if a youth can be provided one of the above therapies with best evidence but getting any counseling at all can be hard and some, especially minority families may decline formal interventions. Any therapy – CBT, DBT, or IPT – acceptable to the youth and family can be helpful. You can often determine if the key components are being provided by asking the teen what they are working on in therapy.

It is clear that checking in regularly with teens who have been through a suicide crisis is crucial to ensure that they continue in therapy long and consistently enough, that the family is involved in treatment, and that they are taught emotion regulation, distress tolerance, and safety planning. Warm, consistent parenting, good parent-child communication, and monitoring are protective factors but also skills that can be boosted to reduce future risk of suicide. When there is family dysfunction, conflict, or weak relationships, getting help for family relationships such as through attachment-based family therapy (ABFT) or family cognitive behavioral therapy is a priority. When bereavement or parental depression is contributing to youth suicidal thoughts, addressing these specifically can reduce suicide risk.

Sometimes family members, even with counseling, are not the best supporters for a teen in pain. When youths nominated their own support team to be informed about risk factors, diagnosis, and treatment plans and to stay in contact weekly there was a 6.6-fold lower risk of death than for nonsupported youth.

But how much of this evidence-based intervention can you ensure from your position in primary care? Refer if you can but regular supportive contacts alone reduce risk so you, trusted staff, school counselors, or even the now more available teletherapists may help. You can work with your patient to fill out a written commitment-to-safety plan (e.g. U. Colorado, CHADIS) of strategies they can use when having suicidal thoughts such as self-distractions, problem-solving, listing things they are looking forward to, things to do to get their mind off suicidal thoughts, and selecting support people to understand their situation with whom to be in regular contact. Any plan needs to take into account how understanding, supportive, and available the family is, factors you are most likely to be able to judge from your ongoing relationship, but that immediate risk may change. Contact within 48 hours, check-in within 1-2 weeks, and provision of crisis hotline information are essential actions.

Recommending home safety is part of routine anticipatory guidance but reduction of lethal means is essential in these cases. Guns are the most lethal method of suicide but discussing safe gun storage has been shown to be more effective than arguing in vain for gun removal. Medication overdose, a common means, can be reduced by not prescribing tricyclics (ineffective and more lethal), and advising parents to lock up all household medications.

You can ask about and coach teens on how to avoid the hazards of participating in online discussion groups, bullying, and cyberbullying (with risk for both perpetrator and victim), all risk factors for suicide. Managing insomnia can improve depression and is within your skills. While pediatricians can’t treat the suicide risk factors of family poverty, unemployment, or loss of culture/identity, we can refer affected families to community resources.

Repeated suicide screens can help but are imperfect, so listen to the child or parent for risk signs such as the youth having self-reported worthlessness, low self-esteem, speaking negatively about self, anhedonia, or poor emotion regulation. Children with impulsive aggression, often familial, are at special risk of suicide. This trait, while more common in ADHD, is not confined to that condition. You can help by optimizing medical management of impulsivity, when appropriate.

Most youth who attempt suicide have one or more mental health diagnoses, particularly major depressive disorder (MDD), eating disorder, ADHD, conduct, or intermittent explosive disorder. When MDD is comorbid with anxiety, suicides increase 9.5-fold. Children on the autism spectrum are more likely to have been bullied and eight times more likely to commit suicide. LGBTQ youth are five times more often bullied and are at high risk for suicide. The more common issues of school failure or substance use also confer risk. While we do our best caring for children with these conditions we may not be thinking about, screening, or monitoring for their suicide risk. It may be important for us to explain that, despite black-box warnings, rates of SSRI prescribing for depression are inversely related to suicides.

Child maltreatment is the highest risk factor for suicide (population attributed risk, or PAR, 9.6%-14.5%), particularly sexual misuse. All together, adverse childhood experiences have a PAR for suicide of 80%. Continuity allows you to monitor for developmental times when distress from past experiences often reemerges, e.g., puberty, dating onset, or divorce. Getting consent and sharing these highly sensitive but potentially triggering factors as well as prior diagnoses with a newly assigned therapist can be helpful to prioritize treatments to prevent a suicide attempt, because they may be difficult to elicit and timeliness is essential.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Brent DA. J Am Acad Child Adolesc Psychiatry. 2019;58(1):25-35.

Cha CB et al. J Child Psychol Psychiatry. 2018;59(4):460-82.

You read “thoughts of being better off dead” on your next patient’s PHQ-9 screen results and break into a sweat. After eliciting the teen’s realistic suicide plan and intent you send him to the ED with his parent for crisis mental health evaluation. When you call the family that evening to follow-up you hear that he was discharged with a “mental health counseling” appointment next week.

Have you done enough to prevent this child from dying at his own hand? I imagine that this haunts you as it does me. It is terrifying to know that, of youth with suicidal ideation, over one-third attempt suicide, most within 1-2 years, and 20%-40% do so without having had a plan.

We now know that certain kinds of psychotherapy have evidence for preventing subsequent suicide in teens at high risk due to suicidal ideation and past attempts. Cognitive behavioral therapy (CBT) has the best evidence including its subtypes for youth with relevant histories: for both suicide and substance use (integrated, or I-CBT), trauma focused (TF-CBT), traumatic grief (CTG-CBT), and CBT-I, for the potent risk factor of insomnia. The other treatment shown to reduce risk is dialectical behavioral therapy–adolescent (DBT-A) focused on strengthening skills in interpersonal effectiveness, mindfulness, distress tolerance, and emotion regulation adapted to youth by adding family therapy and multifamily skills training. Interpersonal psychotherapy (IPT) adapted for suicidal and self-harming adolescents (IPT-SA) also has evidence.

Some school programs have shown moderate efficacy, for example (IPT-A-IN) addresses the social and interpersonal context, and Youth Aware of Mental Health, a school curriculum to increase knowledge, help-seeking, and ways of coping with depression and suicidal behavior, that cut suicide attempts by half.

You may be able to recommend, refer to, or check to see if a youth can be provided one of the above therapies with best evidence but getting any counseling at all can be hard and some, especially minority families may decline formal interventions. Any therapy – CBT, DBT, or IPT – acceptable to the youth and family can be helpful. You can often determine if the key components are being provided by asking the teen what they are working on in therapy.

It is clear that checking in regularly with teens who have been through a suicide crisis is crucial to ensure that they continue in therapy long and consistently enough, that the family is involved in treatment, and that they are taught emotion regulation, distress tolerance, and safety planning. Warm, consistent parenting, good parent-child communication, and monitoring are protective factors but also skills that can be boosted to reduce future risk of suicide. When there is family dysfunction, conflict, or weak relationships, getting help for family relationships such as through attachment-based family therapy (ABFT) or family cognitive behavioral therapy is a priority. When bereavement or parental depression is contributing to youth suicidal thoughts, addressing these specifically can reduce suicide risk.

Sometimes family members, even with counseling, are not the best supporters for a teen in pain. When youths nominated their own support team to be informed about risk factors, diagnosis, and treatment plans and to stay in contact weekly there was a 6.6-fold lower risk of death than for nonsupported youth.

But how much of this evidence-based intervention can you ensure from your position in primary care? Refer if you can but regular supportive contacts alone reduce risk so you, trusted staff, school counselors, or even the now more available teletherapists may help. You can work with your patient to fill out a written commitment-to-safety plan (e.g. U. Colorado, CHADIS) of strategies they can use when having suicidal thoughts such as self-distractions, problem-solving, listing things they are looking forward to, things to do to get their mind off suicidal thoughts, and selecting support people to understand their situation with whom to be in regular contact. Any plan needs to take into account how understanding, supportive, and available the family is, factors you are most likely to be able to judge from your ongoing relationship, but that immediate risk may change. Contact within 48 hours, check-in within 1-2 weeks, and provision of crisis hotline information are essential actions.

Recommending home safety is part of routine anticipatory guidance but reduction of lethal means is essential in these cases. Guns are the most lethal method of suicide but discussing safe gun storage has been shown to be more effective than arguing in vain for gun removal. Medication overdose, a common means, can be reduced by not prescribing tricyclics (ineffective and more lethal), and advising parents to lock up all household medications.

You can ask about and coach teens on how to avoid the hazards of participating in online discussion groups, bullying, and cyberbullying (with risk for both perpetrator and victim), all risk factors for suicide. Managing insomnia can improve depression and is within your skills. While pediatricians can’t treat the suicide risk factors of family poverty, unemployment, or loss of culture/identity, we can refer affected families to community resources.

Repeated suicide screens can help but are imperfect, so listen to the child or parent for risk signs such as the youth having self-reported worthlessness, low self-esteem, speaking negatively about self, anhedonia, or poor emotion regulation. Children with impulsive aggression, often familial, are at special risk of suicide. This trait, while more common in ADHD, is not confined to that condition. You can help by optimizing medical management of impulsivity, when appropriate.

Most youth who attempt suicide have one or more mental health diagnoses, particularly major depressive disorder (MDD), eating disorder, ADHD, conduct, or intermittent explosive disorder. When MDD is comorbid with anxiety, suicides increase 9.5-fold. Children on the autism spectrum are more likely to have been bullied and eight times more likely to commit suicide. LGBTQ youth are five times more often bullied and are at high risk for suicide. The more common issues of school failure or substance use also confer risk. While we do our best caring for children with these conditions we may not be thinking about, screening, or monitoring for their suicide risk. It may be important for us to explain that, despite black-box warnings, rates of SSRI prescribing for depression are inversely related to suicides.

Child maltreatment is the highest risk factor for suicide (population attributed risk, or PAR, 9.6%-14.5%), particularly sexual misuse. All together, adverse childhood experiences have a PAR for suicide of 80%. Continuity allows you to monitor for developmental times when distress from past experiences often reemerges, e.g., puberty, dating onset, or divorce. Getting consent and sharing these highly sensitive but potentially triggering factors as well as prior diagnoses with a newly assigned therapist can be helpful to prioritize treatments to prevent a suicide attempt, because they may be difficult to elicit and timeliness is essential.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Brent DA. J Am Acad Child Adolesc Psychiatry. 2019;58(1):25-35.

Cha CB et al. J Child Psychol Psychiatry. 2018;59(4):460-82.

About 12% of U.S. children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release were hospitalized in 2020. Nearly a third of those had severe disease that required mechanical ventilation or admission to an intensive care unit, according to a new study published in JAMA Network Open on April 9.*

That means about 1 in 9 kids with COVID-19 in this cohort needed hospitalization, and about 1 in 28 had severe COVID-19.

“Although most children with COVID-19 experience mild illness, some children develop serious illness that leads to hospitalization, use of invasive mechanical ventilation, and death,” the researchers wrote.

The research team analyzed discharge data from 869 medical facilities in the Premier Healthcare Database Special COVID-19 Release. They looked for COVID-19 patients ages 18 and under who had an in-patient or emergency department visit between March and October 2020.

More than 20,700 children with COVID-19 had an in-patient or an emergency department visit, and 2,430 were hospitalized with COVID-19. Among those, 756 children had severe COVID-19 and were admitted to an intensive care unit or needed mechanical ventilation.

About 53% of the COVID-19 patients were girls, and about 54% were between ages 12-18. In addition, about 29% had at least one chronic condition.

Similar to COVID-19 studies in adults, Hispanic, Latino and Black patients were overrepresented. About 39% of the children were Hispanic or Latino, and 24% were Black. However, the researchers didn’t find an association between severe COVID-19 and race or ethnicity.

The likelihood of severe COVID-19 increased if the patient had at least one chronic condition, was male, or was between ages 2-11.

“Understanding factors associated with severe COVID-19 disease among children could help inform prevention and control strategies,” they added. “Reducing infection risk through community mitigation strategies is critical for protecting children from COVID-19 and preventing poor outcomes.”

As of April 8, more than 3.54 million U.S. children have tested positive for COVID-19, according to the latest report from the American Academy of Pediatrics and Children’s Hospital Association. Cases among children are increasing slightly, with about 73,000 new cases reported during the first week of April.

Children represent about 13.5% of the COVID-19 cases in the country, according to the report. Among the 24 states that provide data, children represented 1% to 3% of all COVID-19 hospitalizations, and less than 2% of all child COVID-19 cases resulted in hospitalization.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the two groups wrote.

“However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects,” they added.

A version of this article first appeared on WebMD.com.

*CORRECTION, 6/7/21 – This story has been corrected to clarify that the patient sample study reflects only those children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release. A previous version of the story incorrectly implied that 12% of all U.S. children with COVID-19 had required inpatient care.

About 12% of U.S. children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release were hospitalized in 2020. Nearly a third of those had severe disease that required mechanical ventilation or admission to an intensive care unit, according to a new study published in JAMA Network Open on April 9.*

That means about 1 in 9 kids with COVID-19 in this cohort needed hospitalization, and about 1 in 28 had severe COVID-19.

“Although most children with COVID-19 experience mild illness, some children develop serious illness that leads to hospitalization, use of invasive mechanical ventilation, and death,” the researchers wrote.

The research team analyzed discharge data from 869 medical facilities in the Premier Healthcare Database Special COVID-19 Release. They looked for COVID-19 patients ages 18 and under who had an in-patient or emergency department visit between March and October 2020.

More than 20,700 children with COVID-19 had an in-patient or an emergency department visit, and 2,430 were hospitalized with COVID-19. Among those, 756 children had severe COVID-19 and were admitted to an intensive care unit or needed mechanical ventilation.

About 53% of the COVID-19 patients were girls, and about 54% were between ages 12-18. In addition, about 29% had at least one chronic condition.

Similar to COVID-19 studies in adults, Hispanic, Latino and Black patients were overrepresented. About 39% of the children were Hispanic or Latino, and 24% were Black. However, the researchers didn’t find an association between severe COVID-19 and race or ethnicity.

The likelihood of severe COVID-19 increased if the patient had at least one chronic condition, was male, or was between ages 2-11.

“Understanding factors associated with severe COVID-19 disease among children could help inform prevention and control strategies,” they added. “Reducing infection risk through community mitigation strategies is critical for protecting children from COVID-19 and preventing poor outcomes.”

As of April 8, more than 3.54 million U.S. children have tested positive for COVID-19, according to the latest report from the American Academy of Pediatrics and Children’s Hospital Association. Cases among children are increasing slightly, with about 73,000 new cases reported during the first week of April.

Children represent about 13.5% of the COVID-19 cases in the country, according to the report. Among the 24 states that provide data, children represented 1% to 3% of all COVID-19 hospitalizations, and less than 2% of all child COVID-19 cases resulted in hospitalization.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the two groups wrote.

“However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects,” they added.

A version of this article first appeared on WebMD.com.

*CORRECTION, 6/7/21 – This story has been corrected to clarify that the patient sample study reflects only those children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release. A previous version of the story incorrectly implied that 12% of all U.S. children with COVID-19 had required inpatient care.

About 12% of U.S. children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release were hospitalized in 2020. Nearly a third of those had severe disease that required mechanical ventilation or admission to an intensive care unit, according to a new study published in JAMA Network Open on April 9.*

That means about 1 in 9 kids with COVID-19 in this cohort needed hospitalization, and about 1 in 28 had severe COVID-19.

“Although most children with COVID-19 experience mild illness, some children develop serious illness that leads to hospitalization, use of invasive mechanical ventilation, and death,” the researchers wrote.

The research team analyzed discharge data from 869 medical facilities in the Premier Healthcare Database Special COVID-19 Release. They looked for COVID-19 patients ages 18 and under who had an in-patient or emergency department visit between March and October 2020.

More than 20,700 children with COVID-19 had an in-patient or an emergency department visit, and 2,430 were hospitalized with COVID-19. Among those, 756 children had severe COVID-19 and were admitted to an intensive care unit or needed mechanical ventilation.

About 53% of the COVID-19 patients were girls, and about 54% were between ages 12-18. In addition, about 29% had at least one chronic condition.

Similar to COVID-19 studies in adults, Hispanic, Latino and Black patients were overrepresented. About 39% of the children were Hispanic or Latino, and 24% were Black. However, the researchers didn’t find an association between severe COVID-19 and race or ethnicity.

The likelihood of severe COVID-19 increased if the patient had at least one chronic condition, was male, or was between ages 2-11.

“Understanding factors associated with severe COVID-19 disease among children could help inform prevention and control strategies,” they added. “Reducing infection risk through community mitigation strategies is critical for protecting children from COVID-19 and preventing poor outcomes.”

As of April 8, more than 3.54 million U.S. children have tested positive for COVID-19, according to the latest report from the American Academy of Pediatrics and Children’s Hospital Association. Cases among children are increasing slightly, with about 73,000 new cases reported during the first week of April.

Children represent about 13.5% of the COVID-19 cases in the country, according to the report. Among the 24 states that provide data, children represented 1% to 3% of all COVID-19 hospitalizations, and less than 2% of all child COVID-19 cases resulted in hospitalization.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the two groups wrote.

“However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects,” they added.

A version of this article first appeared on WebMD.com.

*CORRECTION, 6/7/21 – This story has been corrected to clarify that the patient sample study reflects only those children who presented to an emergency department or received inpatient care for COVID-19 in a hospital network and were included in the Premier Healthcare Database Special COVID-19 Release. A previous version of the story incorrectly implied that 12% of all U.S. children with COVID-19 had required inpatient care.

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

The Food and Drug Administration has responded to congressional criticism and launched a multiyear plan to reduce the amount of heavy metals such as mercury and arsenic found in baby food.

Catherine Delahaye/DigitalVision/Getty Images

Called “Closer to Zero,” the FDA plan calls for continued scientific investigation, establishes acceptable levels of heavy metals, sets up a way to monitor manufacturers’ compliance, and sets “action levels.”

“Although the FDA’s testing shows that children are not at an immediate health risk from exposure to toxic elements at the levels found in foods, we are starting the plan’s work immediately, with both short- and long-term goals for achieving continued improvements in reducing levels of toxic elements in these foods over time,” the FDA said.

However, Closer to Zero will only make recommendations on heavy metal levels.

“Although action levels are not binding, we have seen that, over the years, our guidance on action levels and other actions have contributed to significant reductions of toxic elements in food,” an FDA spokeswoman wrote in a statement, according to the Washington Post.

A congressional panel said in February 2021 that major brands of commercial baby food routinely have high levels of toxic heavy metals. The House Oversight Committee said this leaves babies at risk for serious developmental and neurologic problems.

The committee sharply criticized the FDA for not taking action.

“Despite the well-known risks of harm to babies from toxic heavy metals, FDA has not taken adequate steps to decrease their presence in baby foods,” the committee said. “FDA has not issued thresholds for the vast majority of toxic heavy metals in baby foods and does not require warning labels on any baby food products.”

A version of this article first appeared on WebMD.com.

The Food and Drug Administration has responded to congressional criticism and launched a multiyear plan to reduce the amount of heavy metals such as mercury and arsenic found in baby food.

Catherine Delahaye/DigitalVision/Getty Images

Called “Closer to Zero,” the FDA plan calls for continued scientific investigation, establishes acceptable levels of heavy metals, sets up a way to monitor manufacturers’ compliance, and sets “action levels.”

“Although the FDA’s testing shows that children are not at an immediate health risk from exposure to toxic elements at the levels found in foods, we are starting the plan’s work immediately, with both short- and long-term goals for achieving continued improvements in reducing levels of toxic elements in these foods over time,” the FDA said.

However, Closer to Zero will only make recommendations on heavy metal levels.

“Although action levels are not binding, we have seen that, over the years, our guidance on action levels and other actions have contributed to significant reductions of toxic elements in food,” an FDA spokeswoman wrote in a statement, according to the Washington Post.

A congressional panel said in February 2021 that major brands of commercial baby food routinely have high levels of toxic heavy metals. The House Oversight Committee said this leaves babies at risk for serious developmental and neurologic problems.

The committee sharply criticized the FDA for not taking action.

“Despite the well-known risks of harm to babies from toxic heavy metals, FDA has not taken adequate steps to decrease their presence in baby foods,” the committee said. “FDA has not issued thresholds for the vast majority of toxic heavy metals in baby foods and does not require warning labels on any baby food products.”

A version of this article first appeared on WebMD.com.

The Food and Drug Administration has responded to congressional criticism and launched a multiyear plan to reduce the amount of heavy metals such as mercury and arsenic found in baby food.

Catherine Delahaye/DigitalVision/Getty Images

Called “Closer to Zero,” the FDA plan calls for continued scientific investigation, establishes acceptable levels of heavy metals, sets up a way to monitor manufacturers’ compliance, and sets “action levels.”

“Although the FDA’s testing shows that children are not at an immediate health risk from exposure to toxic elements at the levels found in foods, we are starting the plan’s work immediately, with both short- and long-term goals for achieving continued improvements in reducing levels of toxic elements in these foods over time,” the FDA said.

However, Closer to Zero will only make recommendations on heavy metal levels.

“Although action levels are not binding, we have seen that, over the years, our guidance on action levels and other actions have contributed to significant reductions of toxic elements in food,” an FDA spokeswoman wrote in a statement, according to the Washington Post.

A congressional panel said in February 2021 that major brands of commercial baby food routinely have high levels of toxic heavy metals. The House Oversight Committee said this leaves babies at risk for serious developmental and neurologic problems.

The committee sharply criticized the FDA for not taking action.

“Despite the well-known risks of harm to babies from toxic heavy metals, FDA has not taken adequate steps to decrease their presence in baby foods,” the committee said. “FDA has not issued thresholds for the vast majority of toxic heavy metals in baby foods and does not require warning labels on any baby food products.”

A version of this article first appeared on WebMD.com.