The inactivated influenza vaccine is more effective than the quadrivalent live attenuated vaccine, according to a study conducted by the Influenza Vaccine Effectiveness Network.

After poor live vaccine performance in young children during the 2013-2014 flu season, the A(H1N1)pdm09 strain was changed. In response to earlier reports that the A(H1N1)pdm09 vaccine strain had poor thermostability, it was updated to A/Bolivia/559/2013 (an A/California/7/2009-like virus) for the 2015-2016 influenza season. Unfortunately, the changes did not increase the vaccine’s immunogenicity. At study sites in Michigan, Pennsylvania, Texas, Washington, and Wisconsin, 6,879 patients aged 6 months or older who presented for acute respiratory illness with a cough of 7 or fewer days were tested for influenza. Of those, 1,309 (19%) tested positive. Vaccination histories were taken from parent interviews and electronic health records.

Yarinca/Stockphoto

The inactivated influenza vaccine is more effective than the quadrivalent live attenuated vaccine, according to a study conducted by the Influenza Vaccine Effectiveness Network.

After poor live vaccine performance in young children during the 2013-2014 flu season, the A(H1N1)pdm09 strain was changed. In response to earlier reports that the A(H1N1)pdm09 vaccine strain had poor thermostability, it was updated to A/Bolivia/559/2013 (an A/California/7/2009-like virus) for the 2015-2016 influenza season. Unfortunately, the changes did not increase the vaccine’s immunogenicity. At study sites in Michigan, Pennsylvania, Texas, Washington, and Wisconsin, 6,879 patients aged 6 months or older who presented for acute respiratory illness with a cough of 7 or fewer days were tested for influenza. Of those, 1,309 (19%) tested positive. Vaccination histories were taken from parent interviews and electronic health records.

Yarinca/Stockphoto

The inactivated influenza vaccine is more effective than the quadrivalent live attenuated vaccine, according to a study conducted by the Influenza Vaccine Effectiveness Network.

After poor live vaccine performance in young children during the 2013-2014 flu season, the A(H1N1)pdm09 strain was changed. In response to earlier reports that the A(H1N1)pdm09 vaccine strain had poor thermostability, it was updated to A/Bolivia/559/2013 (an A/California/7/2009-like virus) for the 2015-2016 influenza season. Unfortunately, the changes did not increase the vaccine’s immunogenicity. At study sites in Michigan, Pennsylvania, Texas, Washington, and Wisconsin, 6,879 patients aged 6 months or older who presented for acute respiratory illness with a cough of 7 or fewer days were tested for influenza. Of those, 1,309 (19%) tested positive. Vaccination histories were taken from parent interviews and electronic health records.

Yarinca/Stockphoto

Mutations that disrupt de novo synthesis of nicotinamide adenine dinucleotide (NAD) were associated with multiple congenital malformations in humans and mice, and supplementing niacin during gestation prevented these malformations in mice, new research suggests.

The malformations include vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL), “a nonrandom combination of congenital defects without a known cause,” wrote Hongjun Shi, PhD, of Victor Chang Cardiac Research Institute, New South Wales, Australia, and colleagues (N Engl J Med. 2017;377:544-52).

Numerous genetic and environmental factors can potentially cause NAD deficiency during gestation and the investigators suggested collectively referring to the resulting malformations as “congenital NAD deficiency disorders.”

Congenital defects can occur together in newborns more often than would be expected by chance, but “in many such cases, it has proved difficult to identify a genetic cause,” the investigators noted. Using genomic sequencing, they looked for possible pathogenic gene variants within four unrelated families in which a person was born with multiple congenital malformations. Next, they evaluated the function of the variants by testing in vitro enzyme activity and measuring relevant plasma metabolites. Finally, they used the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 system to create mouse models with similar variants.

This approach identified variants in two genes encoding enzymes of the kynurenine pathway: 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients had homozygous variants associated with loss-of-function changes in these proteins. A fourth patient had heterozygous variants in the gene encoding KYNU.

“The mutant enzymes had greatly reduced activity in vitro,” the researchers wrote. Patients had decreased circulating levels of NAD, which tryptophan synthesizes through the kynurenine pathway. Notably, mouse embryos lacking the mouse equivalents of HAAO or KYNU also had congenital defects associated with NAD deficiency. Preventing NAD deficiency during gestation averted these defects in mice.

“The NAD de novo synthesis pathway catabolizes tryptophan,” the researchers added. “Although metabolite levels upstream of the block are elevated, and the metabolites have postnatal functions, we found that it is the deficiency in embryonic NAD, downstream of the block, that is disrupting embryogenesis.”

The study was supported by the Australian and New South Wales governments and foundations. The investigators reported having no other financial disclosures.

Mutations that disrupt de novo synthesis of nicotinamide adenine dinucleotide (NAD) were associated with multiple congenital malformations in humans and mice, and supplementing niacin during gestation prevented these malformations in mice, new research suggests.

The malformations include vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL), “a nonrandom combination of congenital defects without a known cause,” wrote Hongjun Shi, PhD, of Victor Chang Cardiac Research Institute, New South Wales, Australia, and colleagues (N Engl J Med. 2017;377:544-52).

Numerous genetic and environmental factors can potentially cause NAD deficiency during gestation and the investigators suggested collectively referring to the resulting malformations as “congenital NAD deficiency disorders.”

Congenital defects can occur together in newborns more often than would be expected by chance, but “in many such cases, it has proved difficult to identify a genetic cause,” the investigators noted. Using genomic sequencing, they looked for possible pathogenic gene variants within four unrelated families in which a person was born with multiple congenital malformations. Next, they evaluated the function of the variants by testing in vitro enzyme activity and measuring relevant plasma metabolites. Finally, they used the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 system to create mouse models with similar variants.

This approach identified variants in two genes encoding enzymes of the kynurenine pathway: 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients had homozygous variants associated with loss-of-function changes in these proteins. A fourth patient had heterozygous variants in the gene encoding KYNU.

“The mutant enzymes had greatly reduced activity in vitro,” the researchers wrote. Patients had decreased circulating levels of NAD, which tryptophan synthesizes through the kynurenine pathway. Notably, mouse embryos lacking the mouse equivalents of HAAO or KYNU also had congenital defects associated with NAD deficiency. Preventing NAD deficiency during gestation averted these defects in mice.

“The NAD de novo synthesis pathway catabolizes tryptophan,” the researchers added. “Although metabolite levels upstream of the block are elevated, and the metabolites have postnatal functions, we found that it is the deficiency in embryonic NAD, downstream of the block, that is disrupting embryogenesis.”

The study was supported by the Australian and New South Wales governments and foundations. The investigators reported having no other financial disclosures.

Mutations that disrupt de novo synthesis of nicotinamide adenine dinucleotide (NAD) were associated with multiple congenital malformations in humans and mice, and supplementing niacin during gestation prevented these malformations in mice, new research suggests.

The malformations include vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL), “a nonrandom combination of congenital defects without a known cause,” wrote Hongjun Shi, PhD, of Victor Chang Cardiac Research Institute, New South Wales, Australia, and colleagues (N Engl J Med. 2017;377:544-52).

Numerous genetic and environmental factors can potentially cause NAD deficiency during gestation and the investigators suggested collectively referring to the resulting malformations as “congenital NAD deficiency disorders.”

Congenital defects can occur together in newborns more often than would be expected by chance, but “in many such cases, it has proved difficult to identify a genetic cause,” the investigators noted. Using genomic sequencing, they looked for possible pathogenic gene variants within four unrelated families in which a person was born with multiple congenital malformations. Next, they evaluated the function of the variants by testing in vitro enzyme activity and measuring relevant plasma metabolites. Finally, they used the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 system to create mouse models with similar variants.

This approach identified variants in two genes encoding enzymes of the kynurenine pathway: 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients had homozygous variants associated with loss-of-function changes in these proteins. A fourth patient had heterozygous variants in the gene encoding KYNU.

“The mutant enzymes had greatly reduced activity in vitro,” the researchers wrote. Patients had decreased circulating levels of NAD, which tryptophan synthesizes through the kynurenine pathway. Notably, mouse embryos lacking the mouse equivalents of HAAO or KYNU also had congenital defects associated with NAD deficiency. Preventing NAD deficiency during gestation averted these defects in mice.

“The NAD de novo synthesis pathway catabolizes tryptophan,” the researchers added. “Although metabolite levels upstream of the block are elevated, and the metabolites have postnatal functions, we found that it is the deficiency in embryonic NAD, downstream of the block, that is disrupting embryogenesis.”

The study was supported by the Australian and New South Wales governments and foundations. The investigators reported having no other financial disclosures.

To improve patient care and outcomes, leading dermatologists offered their recommendations on men’s products. Consideration must be given to:

• bareMinerals SPF 30 Natural Sunscreen
  Bare Escentuals Beauty, Inc
  “I recommend this product to my male patients when they are not wearing a hat. It protects the scalp from UV damage without a heavy greasy finish.”—Shari Lipner, MD, PhD, New York, New York
   
• Ducray Alopexy 5% For Men
  Pierre Fabre Laboratories
  “This dermatologist-dispensed product for men addresses chronic hair loss as well as thinning hair. It contains an optimal level of minoxidil 5% in an elegant unscented formulation and is designed to spray on smoothly and evenly.”—Jeannette Graf, MD, Great Neck, New York
   
• Facial Fuel Energizing Scrub
  Kiehl’s
  “This product is great for oily skin and enlarged pores. The particles in the product allow one to get a deep-clean feeling.”—Gary Goldenberg, MD, New York, New York
   
• Physical Matte UV Defense SPF 50
  SkinCeuticals
  “For men I like to keep things simple. I recommend what I use with the single most important thing being daily sun protection. SkinCeuticals Physical Matte UV Defense SPF 50 is my favorite and I use it after I shave. It goes on smoothly and has a natural tint along with a high SPF.”—Jerome Potozkin, MD, Danville, California
   
• Ultimate Brushless Shave Cream
  Kiehl’s
  “I recommend this product for men with frequent irritation from shaving. This cream-based product helps to provide a close shave without as much irritation from other gel-based products. A small amount goes a long way!”—Anthony M. Rossi, MD, New York, New York

Cutis invites readers to send us their recommendations. Athlete’s foot treatments and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please email your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on men’s products. Consideration must be given to:

• bareMinerals SPF 30 Natural Sunscreen
  Bare Escentuals Beauty, Inc
  “I recommend this product to my male patients when they are not wearing a hat. It protects the scalp from UV damage without a heavy greasy finish.”—Shari Lipner, MD, PhD, New York, New York
   
• Ducray Alopexy 5% For Men
  Pierre Fabre Laboratories
  “This dermatologist-dispensed product for men addresses chronic hair loss as well as thinning hair. It contains an optimal level of minoxidil 5% in an elegant unscented formulation and is designed to spray on smoothly and evenly.”—Jeannette Graf, MD, Great Neck, New York
   
• Facial Fuel Energizing Scrub
  Kiehl’s
  “This product is great for oily skin and enlarged pores. The particles in the product allow one to get a deep-clean feeling.”—Gary Goldenberg, MD, New York, New York
   
• Physical Matte UV Defense SPF 50
  SkinCeuticals
  “For men I like to keep things simple. I recommend what I use with the single most important thing being daily sun protection. SkinCeuticals Physical Matte UV Defense SPF 50 is my favorite and I use it after I shave. It goes on smoothly and has a natural tint along with a high SPF.”—Jerome Potozkin, MD, Danville, California
   
• Ultimate Brushless Shave Cream
  Kiehl’s
  “I recommend this product for men with frequent irritation from shaving. This cream-based product helps to provide a close shave without as much irritation from other gel-based products. A small amount goes a long way!”—Anthony M. Rossi, MD, New York, New York

Cutis invites readers to send us their recommendations. Athlete’s foot treatments and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please email your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on men’s products. Consideration must be given to:

• bareMinerals SPF 30 Natural Sunscreen
  Bare Escentuals Beauty, Inc
  “I recommend this product to my male patients when they are not wearing a hat. It protects the scalp from UV damage without a heavy greasy finish.”—Shari Lipner, MD, PhD, New York, New York
   
• Ducray Alopexy 5% For Men
  Pierre Fabre Laboratories
  “This dermatologist-dispensed product for men addresses chronic hair loss as well as thinning hair. It contains an optimal level of minoxidil 5% in an elegant unscented formulation and is designed to spray on smoothly and evenly.”—Jeannette Graf, MD, Great Neck, New York
   
• Facial Fuel Energizing Scrub
  Kiehl’s
  “This product is great for oily skin and enlarged pores. The particles in the product allow one to get a deep-clean feeling.”—Gary Goldenberg, MD, New York, New York
   
• Physical Matte UV Defense SPF 50
  SkinCeuticals
  “For men I like to keep things simple. I recommend what I use with the single most important thing being daily sun protection. SkinCeuticals Physical Matte UV Defense SPF 50 is my favorite and I use it after I shave. It goes on smoothly and has a natural tint along with a high SPF.”—Jerome Potozkin, MD, Danville, California
   
• Ultimate Brushless Shave Cream
  Kiehl’s
  “I recommend this product for men with frequent irritation from shaving. This cream-based product helps to provide a close shave without as much irritation from other gel-based products. A small amount goes a long way!”—Anthony M. Rossi, MD, New York, New York

Cutis invites readers to send us their recommendations. Athlete’s foot treatments and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please email your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.

“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.

The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).

“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.

The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.

In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.

The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.

The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).

The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.

Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.

“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.

The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).

“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.

The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.

In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.

The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.

The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).

The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.

Children from the poorest families show signs of thicker carotid artery walls that may raise their risk for heart attack and stroke as adults, according to data from a longitudinal study of more than 1,000 families in Australia.

“Understanding when associations between SEP [socioeconomic position] and CVD [cardiovascular disease] first appear may help address the increasing social gradients in CVD outcomes and risk factors,” wrote Richard S. Liu, MD, of the Murdoch Children’s Research Institute, Parkville, Australia, and colleagues.

The researchers reviewed data from 1,477 families in Australia. Socioeconomic position of the children’s families was measured biennially at age 0-1 year and onward, and the researchers used imaging to measure the right carotid arteries of children between age 11 and 12 years. Overall, children in the lowest socioeconomic quartile at age 11-12 years were 46% more likely than those in the highest quartile to have thicker carotid arteries (defined as greater than the 75th percentile).

“In univariable analyses, each quartile increment higher of family SEP was associated with a 3.7-micrometer thicker carotid intima-media thickness [IMT],” and the association remained significant in a multivariate analysis controlling for cardiovascular risk factors including secondhand smoke, body weight, and blood pressure, the researchers wrote.

The socioeconomic status of the family had a greater impact than that of the neighborhood, they noted.

In addition, low socioeconomic status of a child’s family at age 2-3 years was associated with thickness in carotid artery measurements at age 11-12 years.

The study findings were limited by several factors, including a lack of data on the clinical consequences of increased carotid thickness in children, as well as the need for investigation of other signs of subclinical atherosclerosis, the researchers said. However, “consistent evidence showed an association between SEP from early life and midchildhood carotid IMT,” and additional research is needed to explore the impact of household factors on childhood health, they emphasized.

The findings were published online Aug. 9 in the Journal of the American Heart Association (J Am Heart Assoc. 2017;6:e0059255).

The study was funded by the National Health and Medical Research Council of Australia and several research institutions. The researchers had no financial conflicts to disclose.

NEW YORK – A middle-aged patient with Fitzpatrick type V skin comes to the office with a 10-year history of “breakouts” on her face. When asked about topical treatments, she reports that “everything burns or stings,” and says she just has very sensitive skin. What could this be?

[email protected]

On Twitter @karioakes

NEW YORK – A middle-aged patient with Fitzpatrick type V skin comes to the office with a 10-year history of “breakouts” on her face. When asked about topical treatments, she reports that “everything burns or stings,” and says she just has very sensitive skin. What could this be?

[email protected]

On Twitter @karioakes

NEW YORK – A middle-aged patient with Fitzpatrick type V skin comes to the office with a 10-year history of “breakouts” on her face. When asked about topical treatments, she reports that “everything burns or stings,” and says she just has very sensitive skin. What could this be?

[email protected]

On Twitter @karioakes

Human papillomavirus vaccination in girls and women has increased significantly since the implementation of the Affordable Care Act (ACA), according an analysis of federal survey data.

Overall, girls and women were 3.3 times more likely to receive the vaccine (95% confidence interval, 2.0, 5.5; P less than .0001) in the post–ACA implementation period, compared with the pre-ACA period. They were 5.8 times more likely to receive all three doses of the vaccine (95% CI, 2.5-13.6; P = .0001) post ACA, compared with one dose during that period, according to Rosemary Corriero of the University of Georgia, Athens, who is also a fellow at the Centers for Disease Control and Prevention, and her coauthors (J Pediatr Adolesc Gynecol. 2017 Jul 26. doi: 10.1016/j.jpag.2017.07.002).

xrender/Thinkstock

Human papillomavirus vaccination in girls and women has increased significantly since the implementation of the Affordable Care Act (ACA), according an analysis of federal survey data.

Overall, girls and women were 3.3 times more likely to receive the vaccine (95% confidence interval, 2.0, 5.5; P less than .0001) in the post–ACA implementation period, compared with the pre-ACA period. They were 5.8 times more likely to receive all three doses of the vaccine (95% CI, 2.5-13.6; P = .0001) post ACA, compared with one dose during that period, according to Rosemary Corriero of the University of Georgia, Athens, who is also a fellow at the Centers for Disease Control and Prevention, and her coauthors (J Pediatr Adolesc Gynecol. 2017 Jul 26. doi: 10.1016/j.jpag.2017.07.002).

xrender/Thinkstock

Human papillomavirus vaccination in girls and women has increased significantly since the implementation of the Affordable Care Act (ACA), according an analysis of federal survey data.

Overall, girls and women were 3.3 times more likely to receive the vaccine (95% confidence interval, 2.0, 5.5; P less than .0001) in the post–ACA implementation period, compared with the pre-ACA period. They were 5.8 times more likely to receive all three doses of the vaccine (95% CI, 2.5-13.6; P = .0001) post ACA, compared with one dose during that period, according to Rosemary Corriero of the University of Georgia, Athens, who is also a fellow at the Centers for Disease Control and Prevention, and her coauthors (J Pediatr Adolesc Gynecol. 2017 Jul 26. doi: 10.1016/j.jpag.2017.07.002).

xrender/Thinkstock

The antiretroviral therapy (ART) regimen associated with the least risk of adverse birth outcomes among pregnant women with HIV, relative to other regimens, is tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV), according to a new study.

“Our results provide reassurance for the more than 90% of HIV-infected women who live in countries that follow WHO recommendations to use TDF-FTC-EFV,” wrote Rebecca Zash, MD, of Beth Israel Deaconess Medical Center in Boston and her associates in JAMA Pediatrics.

KatarzynaBialasiewicz/thinkstock

• 36.4% of infants exposed to TDF-FTC-EFV.
• 41.7% of infants exposed to TDF-FTC and nevirapine (NVP).
• 44.9% of infants exposed to zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV-R).
• 47.4% of infants exposed to ZDV-3TC-NVP.
• 48.5% of infants exposed to TDF-FTC-LPV-R.

The risk of adverse birth outcomes, compared with exposure to TDF-FTC-EFV, was 15% higher for TDF-FTC-NVP, 21% higher for ZDV-3TC-LPV-R, 30% higher for ZDV-3TC-NVP, and 31% higher for TDF-FTC-LPV-R after researchers adjusted for age and potential sociodemographic confounders.

The risk of severe adverse outcomes for ART exposure from conception was as follows:

• 12.3% for exposure to TDF-FTC-EFV.
• 17.9% for exposure to TDF-FTC-NVP.
• 19.5% for TDF-FTC–LPV-R.
• 20.7% for ZDV-3TC-NVP.
• 23.4% for ZDV-3TC–LPV-R.

The risk for giving birth to an infant small for gestational age was lowest for TDF-FTC-EFV, compared with the other regimens.

“Differences between TDF-FTC-EFV and other ART regimens were greater for small for gestational age than for preterm birth,” suggesting a “drug-specific mechanism at the placental level because the health of the placenta is directly related to fetal growth,” the researchers wrote. “An ART effect at the level of the placenta may also explain why women receiving ART before conception have more adverse outcomes than [do] those who start ART after conception because endothelial dysfunction during placentation would be expected to have a more detrimental effect on the pregnancy,” they added.

The ZDV-3TC-NVP regimen was linked to greater risk for stillbirth, very preterm birth, and neonatal death; the ZDV-3TC-LPV-R regimen was linked to a greater risk of preterm and very preterm birth, as well as neonatal death.

“Our study findings may be difficult to integrate into settings with ART regimen choices beyond those available in Botswana,” the authors wrote. “Whether the magnitude of the differences we found in Botswana will be similar in higher-resource settings is unclear.”

The research was funded by the National Institutes of Health. The authors reported no conflicts of interest.
 

The antiretroviral therapy (ART) regimen associated with the least risk of adverse birth outcomes among pregnant women with HIV, relative to other regimens, is tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV), according to a new study.

“Our results provide reassurance for the more than 90% of HIV-infected women who live in countries that follow WHO recommendations to use TDF-FTC-EFV,” wrote Rebecca Zash, MD, of Beth Israel Deaconess Medical Center in Boston and her associates in JAMA Pediatrics.

KatarzynaBialasiewicz/thinkstock

• 36.4% of infants exposed to TDF-FTC-EFV.
• 41.7% of infants exposed to TDF-FTC and nevirapine (NVP).
• 44.9% of infants exposed to zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV-R).
• 47.4% of infants exposed to ZDV-3TC-NVP.
• 48.5% of infants exposed to TDF-FTC-LPV-R.

The risk of adverse birth outcomes, compared with exposure to TDF-FTC-EFV, was 15% higher for TDF-FTC-NVP, 21% higher for ZDV-3TC-LPV-R, 30% higher for ZDV-3TC-NVP, and 31% higher for TDF-FTC-LPV-R after researchers adjusted for age and potential sociodemographic confounders.

The risk of severe adverse outcomes for ART exposure from conception was as follows:

• 12.3% for exposure to TDF-FTC-EFV.
• 17.9% for exposure to TDF-FTC-NVP.
• 19.5% for TDF-FTC–LPV-R.
• 20.7% for ZDV-3TC-NVP.
• 23.4% for ZDV-3TC–LPV-R.

The risk for giving birth to an infant small for gestational age was lowest for TDF-FTC-EFV, compared with the other regimens.

“Differences between TDF-FTC-EFV and other ART regimens were greater for small for gestational age than for preterm birth,” suggesting a “drug-specific mechanism at the placental level because the health of the placenta is directly related to fetal growth,” the researchers wrote. “An ART effect at the level of the placenta may also explain why women receiving ART before conception have more adverse outcomes than [do] those who start ART after conception because endothelial dysfunction during placentation would be expected to have a more detrimental effect on the pregnancy,” they added.

The ZDV-3TC-NVP regimen was linked to greater risk for stillbirth, very preterm birth, and neonatal death; the ZDV-3TC-LPV-R regimen was linked to a greater risk of preterm and very preterm birth, as well as neonatal death.

“Our study findings may be difficult to integrate into settings with ART regimen choices beyond those available in Botswana,” the authors wrote. “Whether the magnitude of the differences we found in Botswana will be similar in higher-resource settings is unclear.”

The research was funded by the National Institutes of Health. The authors reported no conflicts of interest.
 

The antiretroviral therapy (ART) regimen associated with the least risk of adverse birth outcomes among pregnant women with HIV, relative to other regimens, is tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV), according to a new study.

“Our results provide reassurance for the more than 90% of HIV-infected women who live in countries that follow WHO recommendations to use TDF-FTC-EFV,” wrote Rebecca Zash, MD, of Beth Israel Deaconess Medical Center in Boston and her associates in JAMA Pediatrics.

KatarzynaBialasiewicz/thinkstock

• 36.4% of infants exposed to TDF-FTC-EFV.
• 41.7% of infants exposed to TDF-FTC and nevirapine (NVP).
• 44.9% of infants exposed to zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV-R).
• 47.4% of infants exposed to ZDV-3TC-NVP.
• 48.5% of infants exposed to TDF-FTC-LPV-R.

The risk of adverse birth outcomes, compared with exposure to TDF-FTC-EFV, was 15% higher for TDF-FTC-NVP, 21% higher for ZDV-3TC-LPV-R, 30% higher for ZDV-3TC-NVP, and 31% higher for TDF-FTC-LPV-R after researchers adjusted for age and potential sociodemographic confounders.

The risk of severe adverse outcomes for ART exposure from conception was as follows:

• 12.3% for exposure to TDF-FTC-EFV.
• 17.9% for exposure to TDF-FTC-NVP.
• 19.5% for TDF-FTC–LPV-R.
• 20.7% for ZDV-3TC-NVP.
• 23.4% for ZDV-3TC–LPV-R.

The risk for giving birth to an infant small for gestational age was lowest for TDF-FTC-EFV, compared with the other regimens.

“Differences between TDF-FTC-EFV and other ART regimens were greater for small for gestational age than for preterm birth,” suggesting a “drug-specific mechanism at the placental level because the health of the placenta is directly related to fetal growth,” the researchers wrote. “An ART effect at the level of the placenta may also explain why women receiving ART before conception have more adverse outcomes than [do] those who start ART after conception because endothelial dysfunction during placentation would be expected to have a more detrimental effect on the pregnancy,” they added.

The ZDV-3TC-NVP regimen was linked to greater risk for stillbirth, very preterm birth, and neonatal death; the ZDV-3TC-LPV-R regimen was linked to a greater risk of preterm and very preterm birth, as well as neonatal death.

“Our study findings may be difficult to integrate into settings with ART regimen choices beyond those available in Botswana,” the authors wrote. “Whether the magnitude of the differences we found in Botswana will be similar in higher-resource settings is unclear.”

The research was funded by the National Institutes of Health. The authors reported no conflicts of interest.
 

SAN FRANCISCO – Externalizing problems appear to interfere long term with sleep, whereas sleeping difficulties appear to play a role in children’s development of internalizing problems several years later, new research showed.

“Interventions addressing externalizing difficulties may lead to improvements in sleep, but addressing internalizing difficulties are unlikely to lead to benefits for children’s sleep,” concluded Jon Quach, PhD, of the University of Melbourne and Murdoch Children’s Research Institute, Victoria, Australia, and his colleagues.

Although they also conclude that “addressing sleep problems at earlier time points may reduce both internalizing and externalizing difficulties,” the researchers said the data are inconsistent, only weakly suggesting that sleep influences later externalizing problems at only two different age points, Dr. Quach said when presenting the findings at the Pediatric Academic Societies meeting.

SAN FRANCISCO – Externalizing problems appear to interfere long term with sleep, whereas sleeping difficulties appear to play a role in children’s development of internalizing problems several years later, new research showed.

“Interventions addressing externalizing difficulties may lead to improvements in sleep, but addressing internalizing difficulties are unlikely to lead to benefits for children’s sleep,” concluded Jon Quach, PhD, of the University of Melbourne and Murdoch Children’s Research Institute, Victoria, Australia, and his colleagues.

Although they also conclude that “addressing sleep problems at earlier time points may reduce both internalizing and externalizing difficulties,” the researchers said the data are inconsistent, only weakly suggesting that sleep influences later externalizing problems at only two different age points, Dr. Quach said when presenting the findings at the Pediatric Academic Societies meeting.

SAN FRANCISCO – Externalizing problems appear to interfere long term with sleep, whereas sleeping difficulties appear to play a role in children’s development of internalizing problems several years later, new research showed.

“Interventions addressing externalizing difficulties may lead to improvements in sleep, but addressing internalizing difficulties are unlikely to lead to benefits for children’s sleep,” concluded Jon Quach, PhD, of the University of Melbourne and Murdoch Children’s Research Institute, Victoria, Australia, and his colleagues.

Although they also conclude that “addressing sleep problems at earlier time points may reduce both internalizing and externalizing difficulties,” the researchers said the data are inconsistent, only weakly suggesting that sleep influences later externalizing problems at only two different age points, Dr. Quach said when presenting the findings at the Pediatric Academic Societies meeting.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

To the Editor:

A 22-year-old obese man with untreated mild asthma diagnosed in childhood presented to the emergency department with cheilitis (Figure 1); conjunctivitis; and painful desquamation of the oral mucosa, penis (Figure 2), and perirectal area (Figure 3). Physical examination was notable for palpebral conjunctiva; mucosal involvement with stomatitis (Figure 1B); and isolated 0.5- to 2-cm erosions and ulcerations with positive Nikolsky sign of the scrotum (Figure 2), trunk, back, and arms and legs. Some areas had evidence of hemorrhagic crust, flaccid bullae, and denudation. Few scant targetoid lesions and dusky red macules on the trunk, face, palms, and soles also were present.

One week prior to presentation he had an episode of diarrhea and dyspnea with symptoms of mild heat stroke after working outdoors, and he self-treated with ibuprofen, which he had taken intermittently for years. He was subsequently seen at an outpatient clinic and was prescribed an albuterol inhaler for previously untreated childhood asthma. The patient stated that he inhaled 2 puffs every 6 hours for a total of 3 treatments. Shortly after the last dose, he noticed a tingling sensation of the oral mucosa that developed into a painful 2-cm bullous ulcer. Over the next 3 days, he developed several more oral ulcers and erosions. Three days before admission he developed dysuria and tense bullae at the glans penis. After admission, he developed cheilitis, conjunctivitis, dysuria, odynophagia, and dysphagia to solids. One day after admission, the patient had the onset of systemic symptoms, including cough with worsening dyspnea, fever, chills, hemoptysis, epistaxis, nausea, diarrhea, loss of appetite, joint pain, and myalgia. Review of systems was otherwise negative. A radiograph was performed at admission and was notable for mild atelectasis but was otherwise normal. The chest radiograph was negative for signs of perihilar lymphadenopathy, pleural effusion, pneumothorax, or lobar infiltrates suggestive of bacterial pneumonia. It also did not show signs of patchy opacities or air bronchograms suggestive of an interstitial pneumonia. On admission, he was started on acyclovir, fluconazole, methylprednisolone, nystatin, pantoprazole, acetaminophen, topical bacitracin, oxycodone, and topical silver nitrate.

At the time of admission our patient was afebrile with a normal heart rate, blood pressure, and respiratory rate. However, he was hypoxic, with a pulse oximetry of 86% on room air and 94% on 40% fraction of inspired oxygen. Complete blood cell count, electrolytes, and liver function tests were all within reference range. Urinalysis revealed evidence of scant red blood cells without pyuria, and the erythrocyte sedimentation rate and creatine kinase level were both elevated. Two blood cultures; sputum cultures; and polymerase chain reaction for Mycoplasma pneumoniae, herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus panel, antinuclear antibody screen, and hepatitis B and C panels were all negative. Four punch biopsies were obtained showing full-thickness epidermal necrosis with neutrophils, few dyskeratotic cells, and sparse inflammatory infiltrate compatible with Stevens-Johnson syndrome (SJS).

After hospital admission, the patient’s mucosal desquamation progressively improved. By day 3, he required minimal supplemental oxygen with resolution of bowel symptoms and improved mucosal and skin findings. He was discharged on day 4 with supplemental oxygen and a 7-day course of prednisone, fluconazole, liquid oxycodone, pantoprazole, and acetaminophen. He showed continued improvement at a follow-up outpatient visit 2 days following discharge.

Stevens-Johnson syndrome is a rare severe drug reaction characterized by high fevers, mucosal erosions, tenderness, and skin detachment approximately 1 to 3 weeks after an inciting event.^1,2 Although SJS has been linked to infections and less commonly to immunizations, in more than 80% of cases, SJS is strongly associated with a recent medication change.³ The classes of drugs that have been implicated in SJS most commonly include antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.⁴ Stevens-Johnson syndrome from drug reactions is not uncommon; however, SJS secondary to isolated albuterol use is rare.

Although it is presumed that albuterol was the key inciting factor in our patient’s case of SJS, it also is recognized that mucosal SJS can be associated with M pneumoniae infection. For this reason, we performed polymerase chain reaction for M pneumoniae as well as a chest radiograph to rule out this possibility. In addition, our patient had denied prolonged respiratory symptoms suggestive of a mycoplasma pneumonia infection, such as a prodrome of cough, myalgia, headache, sore throat, or fever. A report of 8 patients with documented SJS and M pneumoniae as well as a review of the literature also demonstrated a mean of 10 days of prodromal symptoms prior to the onset of mucosal lesions and/or a rash.⁵ However, mucosal SJS associated with mycoplasma pneumonia is an important clinical entity that should not be forgotten during the workup of a young patient with mucosal lesions or rash suggestive of SJS.

The exact etiology and mechanism of drug-induced SJS is not well understood at this time; however, evidence suggests that SJS is strongly linked to the host’s inability to detoxify drug metabolites.^6,7 It has been postulated that SJS occurs secondary to a cell-mediated immune response, which activates cytotoxic T lymphocytes and subsequently results in keratinocyte apoptosis. Keratinocyte apoptosis occurs via the CD95-CD95 death receptor and soluble or membrane-bound ligand interaction.^3,8,9 Stevens-Johnson syndrome is thought to occur from an interaction involving an HLA antigen–restricted presentation of drug metabolites to cytotoxic T cells, which can be further supported by evidence of strong genetic associations with HLA antigen alleles B15.02 and B58.01 in the cases of carbamazepine- and allopurinol-induced SJS, respectively.^6,7 However, the genetic associations of specific HLA antigen alleles and polymorphisms with SJS and other cutaneous reactions is thought to be drug specific and HLA antigen subtype specific.⁷ Therefore, it is difficult to determine or correlate the clinical outcomes and manifestations of drug reactions in individualized patients. The precise mechanism of antigenicity of albuterol in initiating this cascade has not yet been determined. However, these investigations provide strong evidence for a correlation between specific HLA antigen haplotypes and occurrence of drug antigenicity resulting in SJS and other cutaneous reactions in susceptible patient populations.

Although the specific molecular pathway and etiology of SJS is not well delineated, pathology in combination with clinical correlation allows for diagnosis. Early-stage biopsies in SJS typically show apoptotic keratinocytes throughout the epidermis. Late-stage biopsies exhibit subepidermal blisters and full-thickness epidermal necrosis.¹ Histopathology was performed on 4-mm punch biopsies of the chest and back and demonstrated full-thickness epidermal necrosis with neutrophils and a few dyskeratotic cells, likely representing a late stage of epidermal involvement. Given the predominance of neutrophils, other diagnostic considerations based solely on the biopsy results included contact dermatitis or phototoxic dermatitis. The remaining inflammatory infiltrate was sparse. Immunofluorescence was pan-negative.

This report illustrates a rare case of SJS from isolated albuterol use. This adverse drug reaction has not been well reported in the literature and may be an important consideration in the management of a patient with asthma.

For the second consecutive year, the Mayo Clinic was named the top hospital in the country by U.S. News & World Report.

Also for the second consecutive year, the Cleveland Clinic is ranked second, while Johns Hopkins Hospital in Baltimore and Massachusetts General Hospital in Boston finished third and fourth – switching their places from last year’s ranking – and UCSF Medical Center in San Francisco is fifth after ranking seventh last year, according to the 2017-2018 Best Hospitals ranking.

[email protected]

For the second consecutive year, the Mayo Clinic was named the top hospital in the country by U.S. News & World Report.

Also for the second consecutive year, the Cleveland Clinic is ranked second, while Johns Hopkins Hospital in Baltimore and Massachusetts General Hospital in Boston finished third and fourth – switching their places from last year’s ranking – and UCSF Medical Center in San Francisco is fifth after ranking seventh last year, according to the 2017-2018 Best Hospitals ranking.

[email protected]

For the second consecutive year, the Mayo Clinic was named the top hospital in the country by U.S. News & World Report.

Also for the second consecutive year, the Cleveland Clinic is ranked second, while Johns Hopkins Hospital in Baltimore and Massachusetts General Hospital in Boston finished third and fourth – switching their places from last year’s ranking – and UCSF Medical Center in San Francisco is fifth after ranking seventh last year, according to the 2017-2018 Best Hospitals ranking.

[email protected]