Infectious Diseases

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

© astridb05/Fotolia.com

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

© astridb05/Fotolia.com

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

© astridb05/Fotolia.com

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

In this column, I will describe the results of a recently published study from my group.¹ We sought to profile Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae (Hflu) and Moraxella catarrhalis (Mcat) in the nasopharynx among 13-valent pneumococcal conjugate vaccine (PCV13)-immunized children, with a focus on the first 6 months of life. The rationale was to provide heretofore unreported contemporary data in a highly PCV13-immunized, community-based child population in the United States. A secondary objective was to assess nasopharyngeal bacterial density because higher density associates with greater likelihood of progression to infection. Thirdly, the serotype distribution and antibiotic susceptibility of pneumococci among children seen in primary care settings in the United States had not been evaluated for strains circulating among infants less than 6 months old and they may differ from strains recovered from older children. Therefore, comparisons were made within the same cohort of children to later child age time points.

Risk factors identified

The study was prospective and collected from a cohort of 101 children in Rochester, N.Y., during 2018-2020. Nasopharyngeal swabs were taken for study at age 1, 2 and 3 weeks, then 1, 2, 4, 6, 9, 12, 15, 18 and 24 months. All children had received PCV13 vaccine according to the Centers for Disease Control and Prevention recommended schedule.

We found two significant risk factors in the first 6 months of life for detection of nasopharyngeal colonization of pneumococcus, Hflu, and Mcat. They were daycare attendance and one or more siblings aged 1-5 years at home.

Colonization by one or more of the three bacteria was detected in only 5% of infants before age 2 months. None of the five children attended daycare but all five had young siblings at home. Pneumococcal colonization was detected in 12%, Hflu in 3%, and Mcat in 21% of nasopharyngeal swabs collected during the first 6 months of life. Nasopharyngeal colonization with the bacteria increased rapidly between age 4 and 6 months of life, coincident with infants going to daycare and other social interaction opportunities. Bacterial density of pneumococcus, Hflu, and Mcat during the first 6 months of life was significantly lower in the nasopharynx compared with bacterial density when samples were collected during child age 7-24 months.

The prevalent pneumococcal serotypes in children up to 6 months old were 23B (17%), 22F (13%), 15B/C (11%), 16F (9%), and 21 (7%), 19F (7%), which differed from those isolated from children age 7-24 months, where serotypes 35B (15%), 21 (10%), 15B (9%), and 23B (7%), 23A (7%) were most commonly observed. Antibiotic resistance among isolates did not significantly differ in comparisons between infants younger than 6 months versus 7- to 24-month-olds.
 

What is the clinical significance?

Colonization of the nasopharynx is a necessary first step in infection pathogenesis (Figure).

Michael Pichichero, MD

In a prior study of a different cohort of 358 prospectively-enrolled children, we sought associations between physician-attended illness visits and bacterial colonization in the first 5 years of life.² We showed that early age of first colonization with pneumococcus, Hflu, and Mcat was associated with respiratory infection proneness and asthma among the children.

Multiple demographic and risk factors may contribute to early life and high-density colonization that in turn may increase risk of infections. High densities and early life pneumococcal colonization in low/middle-income countries might impact PCV responses by induction of immunity tolerance. While it is appealing to study new vaccines in low/middle-income populations with high infection incidence, there are reasons that infection incidence is higher compared with high-income countries like the United States, among them may be early life nasopharyngeal colonization and density of colonization.

Prevalent pneumococcal serotype appear to differ with age. The most common serotypes in the first 6 months of life for the children were 23B> 22F> 16F and 21=19F, but in children 7-24 months, serotypes 35B> 21>15B>23A=23B were most commonly observed. This difference might be due to the impact of antibiotics.³ Pneumococci expressing serotypes 22F and 16F were oxacillin susceptible and antibiotic exposure in the first 6 months of life is very uncommon in our study cohorts. In contrast, all pneumococci expressing 35B capsule were oxacillin resistant and in our cohorts antibiotic exposures are common among 7- to 24-month-olds.

In conclusion, we determined that children in the first 6 months of life seen in pediatric primary care settings in Rochester, N.Y., have very low prevalence and low-density colonization of pneumococcus, Hflu, and Mcat compared with 7- to 24-month olds. Our results may explain the significantly lower rates of infections caused by pneumococci, Hflu, and Mcat in infants younger than 6 months old compared with low/middle-income countries.
 

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to disclose.

References

1. Kaur R and Pichichero M. Colonization, density, and antibiotic resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13 vaccinated infants in the first six months of life in Rochester, New York. J Pediatric Infect Dis Soc. 2023 Apr 18;12(3):135-42.

2. Chapman T et al. Nasopharyngeal colonization with pathobionts is associated with susceptibility to respiratory illnesses in young children. PLoS One. 2020 Dec 11;15(12):e0243942. doi: 10.1371/journal.pone.0243942.

3. Chapman TJ et al. Antibiotic use and vaccine antibody levels. Pediatrics 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

In this column, I will describe the results of a recently published study from my group.¹ We sought to profile Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae (Hflu) and Moraxella catarrhalis (Mcat) in the nasopharynx among 13-valent pneumococcal conjugate vaccine (PCV13)-immunized children, with a focus on the first 6 months of life. The rationale was to provide heretofore unreported contemporary data in a highly PCV13-immunized, community-based child population in the United States. A secondary objective was to assess nasopharyngeal bacterial density because higher density associates with greater likelihood of progression to infection. Thirdly, the serotype distribution and antibiotic susceptibility of pneumococci among children seen in primary care settings in the United States had not been evaluated for strains circulating among infants less than 6 months old and they may differ from strains recovered from older children. Therefore, comparisons were made within the same cohort of children to later child age time points.

Risk factors identified

The study was prospective and collected from a cohort of 101 children in Rochester, N.Y., during 2018-2020. Nasopharyngeal swabs were taken for study at age 1, 2 and 3 weeks, then 1, 2, 4, 6, 9, 12, 15, 18 and 24 months. All children had received PCV13 vaccine according to the Centers for Disease Control and Prevention recommended schedule.

We found two significant risk factors in the first 6 months of life for detection of nasopharyngeal colonization of pneumococcus, Hflu, and Mcat. They were daycare attendance and one or more siblings aged 1-5 years at home.

Colonization by one or more of the three bacteria was detected in only 5% of infants before age 2 months. None of the five children attended daycare but all five had young siblings at home. Pneumococcal colonization was detected in 12%, Hflu in 3%, and Mcat in 21% of nasopharyngeal swabs collected during the first 6 months of life. Nasopharyngeal colonization with the bacteria increased rapidly between age 4 and 6 months of life, coincident with infants going to daycare and other social interaction opportunities. Bacterial density of pneumococcus, Hflu, and Mcat during the first 6 months of life was significantly lower in the nasopharynx compared with bacterial density when samples were collected during child age 7-24 months.

The prevalent pneumococcal serotypes in children up to 6 months old were 23B (17%), 22F (13%), 15B/C (11%), 16F (9%), and 21 (7%), 19F (7%), which differed from those isolated from children age 7-24 months, where serotypes 35B (15%), 21 (10%), 15B (9%), and 23B (7%), 23A (7%) were most commonly observed. Antibiotic resistance among isolates did not significantly differ in comparisons between infants younger than 6 months versus 7- to 24-month-olds.
 

What is the clinical significance?

Colonization of the nasopharynx is a necessary first step in infection pathogenesis (Figure).

Michael Pichichero, MD

In a prior study of a different cohort of 358 prospectively-enrolled children, we sought associations between physician-attended illness visits and bacterial colonization in the first 5 years of life.² We showed that early age of first colonization with pneumococcus, Hflu, and Mcat was associated with respiratory infection proneness and asthma among the children.

Multiple demographic and risk factors may contribute to early life and high-density colonization that in turn may increase risk of infections. High densities and early life pneumococcal colonization in low/middle-income countries might impact PCV responses by induction of immunity tolerance. While it is appealing to study new vaccines in low/middle-income populations with high infection incidence, there are reasons that infection incidence is higher compared with high-income countries like the United States, among them may be early life nasopharyngeal colonization and density of colonization.

Prevalent pneumococcal serotype appear to differ with age. The most common serotypes in the first 6 months of life for the children were 23B> 22F> 16F and 21=19F, but in children 7-24 months, serotypes 35B> 21>15B>23A=23B were most commonly observed. This difference might be due to the impact of antibiotics.³ Pneumococci expressing serotypes 22F and 16F were oxacillin susceptible and antibiotic exposure in the first 6 months of life is very uncommon in our study cohorts. In contrast, all pneumococci expressing 35B capsule were oxacillin resistant and in our cohorts antibiotic exposures are common among 7- to 24-month-olds.

In conclusion, we determined that children in the first 6 months of life seen in pediatric primary care settings in Rochester, N.Y., have very low prevalence and low-density colonization of pneumococcus, Hflu, and Mcat compared with 7- to 24-month olds. Our results may explain the significantly lower rates of infections caused by pneumococci, Hflu, and Mcat in infants younger than 6 months old compared with low/middle-income countries.
 

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to disclose.

References

1. Kaur R and Pichichero M. Colonization, density, and antibiotic resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13 vaccinated infants in the first six months of life in Rochester, New York. J Pediatric Infect Dis Soc. 2023 Apr 18;12(3):135-42.

2. Chapman T et al. Nasopharyngeal colonization with pathobionts is associated with susceptibility to respiratory illnesses in young children. PLoS One. 2020 Dec 11;15(12):e0243942. doi: 10.1371/journal.pone.0243942.

3. Chapman TJ et al. Antibiotic use and vaccine antibody levels. Pediatrics 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

In this column, I will describe the results of a recently published study from my group.¹ We sought to profile Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae (Hflu) and Moraxella catarrhalis (Mcat) in the nasopharynx among 13-valent pneumococcal conjugate vaccine (PCV13)-immunized children, with a focus on the first 6 months of life. The rationale was to provide heretofore unreported contemporary data in a highly PCV13-immunized, community-based child population in the United States. A secondary objective was to assess nasopharyngeal bacterial density because higher density associates with greater likelihood of progression to infection. Thirdly, the serotype distribution and antibiotic susceptibility of pneumococci among children seen in primary care settings in the United States had not been evaluated for strains circulating among infants less than 6 months old and they may differ from strains recovered from older children. Therefore, comparisons were made within the same cohort of children to later child age time points.

Risk factors identified

The study was prospective and collected from a cohort of 101 children in Rochester, N.Y., during 2018-2020. Nasopharyngeal swabs were taken for study at age 1, 2 and 3 weeks, then 1, 2, 4, 6, 9, 12, 15, 18 and 24 months. All children had received PCV13 vaccine according to the Centers for Disease Control and Prevention recommended schedule.

We found two significant risk factors in the first 6 months of life for detection of nasopharyngeal colonization of pneumococcus, Hflu, and Mcat. They were daycare attendance and one or more siblings aged 1-5 years at home.

Colonization by one or more of the three bacteria was detected in only 5% of infants before age 2 months. None of the five children attended daycare but all five had young siblings at home. Pneumococcal colonization was detected in 12%, Hflu in 3%, and Mcat in 21% of nasopharyngeal swabs collected during the first 6 months of life. Nasopharyngeal colonization with the bacteria increased rapidly between age 4 and 6 months of life, coincident with infants going to daycare and other social interaction opportunities. Bacterial density of pneumococcus, Hflu, and Mcat during the first 6 months of life was significantly lower in the nasopharynx compared with bacterial density when samples were collected during child age 7-24 months.

The prevalent pneumococcal serotypes in children up to 6 months old were 23B (17%), 22F (13%), 15B/C (11%), 16F (9%), and 21 (7%), 19F (7%), which differed from those isolated from children age 7-24 months, where serotypes 35B (15%), 21 (10%), 15B (9%), and 23B (7%), 23A (7%) were most commonly observed. Antibiotic resistance among isolates did not significantly differ in comparisons between infants younger than 6 months versus 7- to 24-month-olds.
 

What is the clinical significance?

Colonization of the nasopharynx is a necessary first step in infection pathogenesis (Figure).

Michael Pichichero, MD

In a prior study of a different cohort of 358 prospectively-enrolled children, we sought associations between physician-attended illness visits and bacterial colonization in the first 5 years of life.² We showed that early age of first colonization with pneumococcus, Hflu, and Mcat was associated with respiratory infection proneness and asthma among the children.

Multiple demographic and risk factors may contribute to early life and high-density colonization that in turn may increase risk of infections. High densities and early life pneumococcal colonization in low/middle-income countries might impact PCV responses by induction of immunity tolerance. While it is appealing to study new vaccines in low/middle-income populations with high infection incidence, there are reasons that infection incidence is higher compared with high-income countries like the United States, among them may be early life nasopharyngeal colonization and density of colonization.

Prevalent pneumococcal serotype appear to differ with age. The most common serotypes in the first 6 months of life for the children were 23B> 22F> 16F and 21=19F, but in children 7-24 months, serotypes 35B> 21>15B>23A=23B were most commonly observed. This difference might be due to the impact of antibiotics.³ Pneumococci expressing serotypes 22F and 16F were oxacillin susceptible and antibiotic exposure in the first 6 months of life is very uncommon in our study cohorts. In contrast, all pneumococci expressing 35B capsule were oxacillin resistant and in our cohorts antibiotic exposures are common among 7- to 24-month-olds.

In conclusion, we determined that children in the first 6 months of life seen in pediatric primary care settings in Rochester, N.Y., have very low prevalence and low-density colonization of pneumococcus, Hflu, and Mcat compared with 7- to 24-month olds. Our results may explain the significantly lower rates of infections caused by pneumococci, Hflu, and Mcat in infants younger than 6 months old compared with low/middle-income countries.
 

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to disclose.

References

1. Kaur R and Pichichero M. Colonization, density, and antibiotic resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13 vaccinated infants in the first six months of life in Rochester, New York. J Pediatric Infect Dis Soc. 2023 Apr 18;12(3):135-42.

2. Chapman T et al. Nasopharyngeal colonization with pathobionts is associated with susceptibility to respiratory illnesses in young children. PLoS One. 2020 Dec 11;15(12):e0243942. doi: 10.1371/journal.pone.0243942.

3. Chapman TJ et al. Antibiotic use and vaccine antibody levels. Pediatrics 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

TOPLINE:

COVID-19 vaccines from Moderna and Pfizer-BioNTech are safe for children under age 5 years, according to findings from a study funded by the Centers for Disease Control and Prevention.

METHODOLOGY:

• Data came from the Vaccine Safety Datalink, which gathers information from eight health systems in the United States.
• Analyzed data from 135,005 doses given to children age 4 and younger who received the Pfizer-BioNTech , and 112,006 doses given to children aged 5 and younger who received the Moderna version.
• Assessed for 23 safety outcomes, including myocarditis, pericarditis, and seizures.

TAKEAWAY:

• None of the adverse outcomes, including myocarditis or pericarditis, was detected among the children in the 21 days following receipt of either vaccine.
• One case of hemorrhagic stroke and one case of pulmonary embolism occurred after vaccination but these were linked to preexisting congenital abnormalities.

IN PRACTICE:

“These results can provide reassurance to clinicians, parents, and policymakers alike.”

STUDY DETAILS:

The study was led by Kristin Goddard, MPH, a researcher at the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and was funded by the Centers for Disease Control and Prevention.

LIMITATIONS:

The researchers reported low statistical power for early analysis, especially for rare outcomes. In addition, fewer than 25% of children in the database had received a vaccine at the time of analysis.  

DISCLOSURES:

A coauthor reported receiving funding from Janssen Vaccines and Prevention for a study unrelated to COVID-19 vaccines. Another coauthor reported receiving grants from Pfizer in 2019 for clinical trials for coronavirus vaccines, and from Merck, GSK, and Sanofi Pasteur for unrelated research.

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

TOPLINE:

COVID-19 vaccines from Moderna and Pfizer-BioNTech are safe for children under age 5 years, according to findings from a study funded by the Centers for Disease Control and Prevention.

METHODOLOGY:

• Data came from the Vaccine Safety Datalink, which gathers information from eight health systems in the United States.
• Analyzed data from 135,005 doses given to children age 4 and younger who received the Pfizer-BioNTech , and 112,006 doses given to children aged 5 and younger who received the Moderna version.
• Assessed for 23 safety outcomes, including myocarditis, pericarditis, and seizures.

TAKEAWAY:

• None of the adverse outcomes, including myocarditis or pericarditis, was detected among the children in the 21 days following receipt of either vaccine.
• One case of hemorrhagic stroke and one case of pulmonary embolism occurred after vaccination but these were linked to preexisting congenital abnormalities.

IN PRACTICE:

“These results can provide reassurance to clinicians, parents, and policymakers alike.”

STUDY DETAILS:

The study was led by Kristin Goddard, MPH, a researcher at the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and was funded by the Centers for Disease Control and Prevention.

LIMITATIONS:

The researchers reported low statistical power for early analysis, especially for rare outcomes. In addition, fewer than 25% of children in the database had received a vaccine at the time of analysis.  

DISCLOSURES:

A coauthor reported receiving funding from Janssen Vaccines and Prevention for a study unrelated to COVID-19 vaccines. Another coauthor reported receiving grants from Pfizer in 2019 for clinical trials for coronavirus vaccines, and from Merck, GSK, and Sanofi Pasteur for unrelated research.

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

TOPLINE:

COVID-19 vaccines from Moderna and Pfizer-BioNTech are safe for children under age 5 years, according to findings from a study funded by the Centers for Disease Control and Prevention.

METHODOLOGY:

• Data came from the Vaccine Safety Datalink, which gathers information from eight health systems in the United States.
• Analyzed data from 135,005 doses given to children age 4 and younger who received the Pfizer-BioNTech , and 112,006 doses given to children aged 5 and younger who received the Moderna version.
• Assessed for 23 safety outcomes, including myocarditis, pericarditis, and seizures.

TAKEAWAY:

• None of the adverse outcomes, including myocarditis or pericarditis, was detected among the children in the 21 days following receipt of either vaccine.
• One case of hemorrhagic stroke and one case of pulmonary embolism occurred after vaccination but these were linked to preexisting congenital abnormalities.

IN PRACTICE:

“These results can provide reassurance to clinicians, parents, and policymakers alike.”

STUDY DETAILS:

The study was led by Kristin Goddard, MPH, a researcher at the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and was funded by the Centers for Disease Control and Prevention.

LIMITATIONS:

The researchers reported low statistical power for early analysis, especially for rare outcomes. In addition, fewer than 25% of children in the database had received a vaccine at the time of analysis.  

DISCLOSURES:

A coauthor reported receiving funding from Janssen Vaccines and Prevention for a study unrelated to COVID-19 vaccines. Another coauthor reported receiving grants from Pfizer in 2019 for clinical trials for coronavirus vaccines, and from Merck, GSK, and Sanofi Pasteur for unrelated research.

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

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

Throughout the COVID-19 pandemic, there has been a striking paucity of representations of patients with skin of color (SOC) in the dermatology literature. Was COVID-19 underdiagnosed in this patient population due to a lack of patient-centered resources and inadequate dermatology training; reduced access to care, resulting from social determinants of health and reduced skin-color concordance; or the absence of population-based prevalence studies?

Tan et al¹ reviewed 51 articles describing skin findings secondary to COVID-19. Patients were stratified by country of origin, which yielded an increased prevalence of cutaneous manifestations among Americans and Europeans compared to Asians, but patients were not stratified by race.¹ However, in one case series of 318 predominantly American patients, 89% were White and 0.7% were Black.² This systematic review by Tan et al¹ suggested that skin manifestations of COVID-19 were present in patients with SOC but less frequently than in White patients. However, case series are not a strong proxy for population-level prevalence.

More broadly, patients with SOC are underrepresented in Google image search results, as the medical resource websites (eg, DermNet [https://dermnetnz.org], MedicalNewsToday [www.medicalnewstoday.com], and Healthline [www.healthline.com]) are lacking these images.³ As a result, it is difficult for patients with SOC to recognize diseases presenting in darker skin types. This same tendency may exist for COVID-19 skin manifestations. A systematic review found that articles describing cutaneous manifestations of COVID-19 almost exclusively presented images of lighter skin and completely omitted darker skin.⁴ If images of patients with SOC are absent from online resources, it is increasingly unlikely for these patients to recognize if their skin lesions are associated with COVID-19, which may result in a decrease in the number of patients with SOC presenting with skin lesions secondary to COVID-19, thereby influencing the representation of patients with SOC in case studies.

The lack of representation of SOC in online resources mirrors the paucity of images in dermatology textbooks. According to a search of 7170 images in major dermatology textbooks, most images depicted light or white skin (80.6%), followed by medium or brown skin in 15.5% of images and dark or black skin in only 3.9%.⁵ Physicians rely on online and print resources for making diagnoses; inadequate resources highlight a component of a larger issue: inadequate training of dermatologists in SOC. In a survey of American dermatologists and dermatology residents (N=262), 47% thought that their medical education had not adequately trained them on skin conditions in Black patients.⁶

A lack of adequate training for dermatologists may decrease the rate of correct diagnosis of skin lesions secondary to COVID-19 in patients with SOC. A lack of trust in the health care system and social determinants of health may hinder patients with SOC from seeking medical help. Dermatology is the second least diverse of medical specialties; only 3% of dermatologists are Black.⁷ This is impactful: First, because minority physicians are increasingly likely to provide care for patients of the same race or background, and second, because race-concordant physician visits are associated with greater patient-reported positive affect.⁷ A lack of availability of race-concordant physicians or physicians with perceived cultural competence may deter patients with SOC from seeking help, which may be further prevalent in dermatologic practice.

Barriers at all levels of social determinants of health hinder access to health care. Patients with SOC experience greater housing insecurity, increased reliance on public transportation, more issues with health literacy, and limited English-language fluency.⁸ Combined, these factors equate to decreased access to health care resources and subsequently a lack of inclusion in case studies.

COVID-19 infection disproportionately affects patients with SOC,⁸ but there is a clear lack of representation of SOC in the COVID-19 dermatology literature. It is imperative to investigate factors that may contribute to this inequity. Recognizing skin manifestations can play a role in diagnosing COVID-19; increased awareness of its presentation in darker skin types may help bridge existing racial inequities. It is vital that physicians receive adequate resources and training to be able to recognize cutaneous manifestations of COVID-19 in all skin types. Finally, it is important to recognize that the lack of representation of SOC in the COVID-19 literature represents a larger trend that exists in dermatologic research that warrants further investigation and advocacy for inclusivity.

Scabies is caused by cutaneous ectoparasitic infection by the mite Sarcoptes scabiei var hominis. The infection is highly contagious via direct skin-to-skin contact or indirectly through infested bedding, clothing or fomites.^1,2 Scabies occurs at all ages, in all ethnic groups, and at all socioeconomic levels.¹ Analysis by the Global Burden of Disease estimates that 200 million individuals have been infected with scabies worldwide. The World Health Organization has declared scabies a neglected tropical disease.³

Crusted scabies is a severe and rare form of scabies, with hyperinfestation of thousands to millions of mites, and more commonly is associated with immunosuppressed states, including HIV and hematologic malignancies.^1,2,4 Crusted scabies has a high mortality rate due to sepsis when left untreated.^3,5

Occasionally, iatrogenic immunosuppression contributes to the development of crusted scabies.^1,2 Iatrogenic immunosuppression leading to crusted scabies most commonly occurs secondary to immunosuppression after bone marrow or solid organ transplantation.⁶ Less often, crusted scabies is caused by iatrogenic immunosuppression from other clinical scenarios.^1,2

We describe a patient with iatrogenic immunosuppression due to azathioprine-induced myelosuppression for the treatment of granulomatosis with polyangiitis (GPA) who developed crusted scabies that clinically presented as erythroderma. Crusted scabies should be included in the differential diagnosis of erythroderma, especially in the setting of iatrogenic immunosuppression, for timely and appropriate management.

Case Report

An 84-year-old man presented with worsening pruritus, erythema, and thick yellow scale that progressed to erythroderma over the last 2 weeks. He was diagnosed with GPA 6 months prior to presentation and was treated with azathioprine 150 mg/d, prednisone 10 mg/d, and sulfamethoxazole 800 mg plus trimethoprim 160 mg twice weekly for prophylaxis against Pneumocystis jirovecii pneumonia.

Three weeks prior to presentation, the patient was hospitalized for pancytopenia attributed to azathioprine-induced myelosuppression (hemoglobin, 6.1 g/dL [reference range, 13.5–18.0 g/dL]; hematocrit, 17.5% [reference range, 42%–52%]; white blood cell count, 1.66×10³/μL [reference range, 4.0–10.5×10³/μL]; platelet count, 146×10³/μL [reference range, 150–450×10³/μL]; absolute neutrophil count, 1.29×10³/μL [reference range, 1.4–6.5×10³/μL]). He was transferred to a skilled nursing facility after discharge and referred to dermatology for evaluation of the worsening pruritic rash.

At the current presentation, the patient denied close contact with anyone who had a similar rash at home or at the skilled nursing facility. Physical examination revealed diffuse erythroderma with yellow scale on the scalp, trunk, arms, and legs (Figure 1). The palms showed scattered 2- to 3-mm pustules. The mucosal surfaces did not have lesions. A punch biopsy of a pustule from the right arm revealed focal spongiosis, parakeratosis, and acanthosis, as well as a perivascular and interstitial mixed inflammatory infiltrate with lymphocytes and eosinophils. Organisms morphologically compatible with scabies were found in the stratum corneum (Figure 2). Another punch biopsy of a pustule from the right arm was performed for direct immunofluorescence (DIF) and was negative for immunoglobulin deposition. Mineral oil preparation from pustules on the palm was positive for mites.

The patient was treated with permethrin cream 5% and oral ivermectin 200 μg/kg on day 1 and day 10. The prednisone dosage was increased from 10 mg/d to 50 mg/d and tapered over 2 weeks to treat the symptomatic rash and GPA. He remains on maintenance rituximab for GPA, without recurrence of scabies.

Comment

Pathogenesis—As an obligate parasite, S scabiei spends its entire life cycle within the host. Impregnated female mites burrow into the epidermis after mating and lay eggs daily for 1 to 2 months. Eggs hatch 2 or 3 days later. Larvae then migrate to the skin surface; burrow into the stratum corneum, where they mature into adults; and then mate on the skin surface.^1,4

Clinical Presentation and Sequelae—Typically, scabies presents 2 to 6 weeks after initial exposure with generalized and intense itching and inflammatory pruritic papules on the finger webs, wrists, elbows, axillae, buttocks, umbilicus, genitalia, and areolae.¹ Burrows are specific for scabies but may not always be present. Often, there are nonspecific secondary lesions, including excoriations, dermatitis, and impetiginization.

Complications of scabies can be severe, with initial colonization and infection of the skin resulting in impetigo and cellulitis. Systematic sequelae from local skin infection include post-streptococcal glomerulonephritis, rheumatic fever, and sepsis. Mortality from sepsis in scabies can be high.^3,5

Classic Crusted Scabies and Other Variants—Crusted scabies presents with psoriasiform hyperkeratotic plaques involving the hands and feet with potential nail involvement that can become more generalized.¹ Alterations in CD4⁺ T-cell function have been implicated in the development of crusted scabies, in which an excessive helper T cell (T_H2) response is elicited against the ectoparasite, which may help explain the intense pruritus of scabies.⁶ Occasionally, iatrogenic immunosuppression contributes to development of crusted scabies,¹ as was the case with our patient. However, it is rare for crusted scabies to present with erythroderma.⁷

Other atypical presentations of scabies include a seborrheic dermatitis–like presentation in infants, nodular lesions in the groin and axillae in more chronic scabies, and vesicles or bullous lesions.¹

Diagnosis—Identification of mites, eggs, or feces is necessary for definitive diagnosis of scabies.⁸ These materials can be obtained through skin scrapings with mineral oil and observed under light microscopy or direct dermoscopy. Multiple scrapings on many lesions should be performed because failure to identify mites can be common and does not rule out scabies. Dermoscopic examination of active lesions under low power also can be helpful, given that identification of dark brown triangular structures can correspond to visualization of the pigmented anterior section of the mite.^9-11 A skin biopsy can help identify mites, but histopathology often shows a nonspecific hypersensitivity reaction.¹² Therefore, empiric treatment often is necessary.

Differential Diagnosis—The differential diagnosis of erythroderma is broad and includes a drug eruption; Sézary syndrome; and pre-existing skin diseases, including psoriasis, atopic dermatitis, pityriasis rubra pilaris, pemphigus foliaceus, and bullous pemphigoid. Histopathology is critical to differentiate these diagnoses. Bullous pemphigoid and pemphigus foliaceus are immunobullous diseases that typically are positive for immunoglobulin deposition on DIF. In rare cases, scabies also can present with bullae and positive DIF test results.¹³

Treatment—First-line treatment of crusted scabies in the United States is permethrin cream 5%, followed by oral ivermectin 200 μg/kg.^4,5,14,15 Other scabicides include topicals such as benzyl benzoate 10% to 25%; precipitated sulfur 2% to 10%; crotamiton 10%; malathion 0.5%; and lindane 1%.⁵ The association of neurotoxicity with lindane has considerably reduced the drug’s use.¹

During treatment of scabies, it is important to isolate patients to mitigate the possibility of spread.⁴ Pruritus can persist for a few weeks after completion of therapy.⁵ Patients should be closely monitored to ensure that this symptom is secondary to skin inflammation and not incomplete treatment.

Treatment of crusted scabies may require repeated treatments to decrease the notable mite burden as well as the associated crusting and scale. Adding a keratolytic such as 5% to 10% salicylic acid in petrolatum to the treatment regimen may be useful for breaking up thick scale.⁵

Immunosuppression—With numerous immunomodulatory drugs for treating autoimmunity comes an increased risk for iatrogenic immunosuppression that may contribute to the development of crusted scabies.¹⁶ In a number of autoimmune diseases such as rheumatoid arthritis,^17-19 psoriasis,^20,21 pemphigus vulgaris,²² systemic lupus erythematosus,²³ systemic sclerosis,^22,24 bullous pemphigoid,^25,26 and dermatomyositis,²⁷ patients have developed crusted scabies secondary to treatment-related immunosuppression. These immunosuppressive therapies include systemic steroids,^22-24,26-31 methotrexate,²³ infliximab,¹⁸ adalimumab,²¹ toclizumab,¹⁹ and etanercept.²⁰ In a case of drug-induced Stevens-Johnson syndrome, the patient developed crusted scabies during long-term use of oral steroids.²²

Patients with a malignancy who are being treated with chemotherapy also can develop crusted scabies.²⁸ Crusted scabies has even been associated with long-term topical steroid^32-34 and topical calcineurin inhibitor use.¹⁶

Iatrogenic immunosuppression in our patient resulted from treatment of GPA with azathioprine, an immunosuppressive drug that acts as an antagonist of the breakdown of purines, leading to inhibition of DNA, RNA, and protein synthesis.³⁵ On occasion, azathioprine can induce immunosuppression in the form of myelosuppression and resulting pancytopenia, as was the case with our patient.

Conclusion

Although scabies is designated as a neglected tropical disease by the World Health Organization, it still causes a notable burden worldwide, regardless of the economics. Our case highlights an unusual presentation of scabies as erythroderma in the setting of iatrogenic immunosuppression from azathioprine use. Dermatologists should consider crusted scabies in the differential diagnosis of erythroderma, especially in immunocompromised patients, to avoid delays in diagnosis and treatment. Immunosuppressive therapy is an important mainstay in the treatment of many conditions, but it is important to consider that these medications can place patients at an increased risk for rare opportunistic infections. Therefore, patients receiving such treatment should be closely monitored.

Scabies is caused by cutaneous ectoparasitic infection by the mite Sarcoptes scabiei var hominis. The infection is highly contagious via direct skin-to-skin contact or indirectly through infested bedding, clothing or fomites.^1,2 Scabies occurs at all ages, in all ethnic groups, and at all socioeconomic levels.¹ Analysis by the Global Burden of Disease estimates that 200 million individuals have been infected with scabies worldwide. The World Health Organization has declared scabies a neglected tropical disease.³

Crusted scabies is a severe and rare form of scabies, with hyperinfestation of thousands to millions of mites, and more commonly is associated with immunosuppressed states, including HIV and hematologic malignancies.^1,2,4 Crusted scabies has a high mortality rate due to sepsis when left untreated.^3,5

Occasionally, iatrogenic immunosuppression contributes to the development of crusted scabies.^1,2 Iatrogenic immunosuppression leading to crusted scabies most commonly occurs secondary to immunosuppression after bone marrow or solid organ transplantation.⁶ Less often, crusted scabies is caused by iatrogenic immunosuppression from other clinical scenarios.^1,2

We describe a patient with iatrogenic immunosuppression due to azathioprine-induced myelosuppression for the treatment of granulomatosis with polyangiitis (GPA) who developed crusted scabies that clinically presented as erythroderma. Crusted scabies should be included in the differential diagnosis of erythroderma, especially in the setting of iatrogenic immunosuppression, for timely and appropriate management.

Case Report

An 84-year-old man presented with worsening pruritus, erythema, and thick yellow scale that progressed to erythroderma over the last 2 weeks. He was diagnosed with GPA 6 months prior to presentation and was treated with azathioprine 150 mg/d, prednisone 10 mg/d, and sulfamethoxazole 800 mg plus trimethoprim 160 mg twice weekly for prophylaxis against Pneumocystis jirovecii pneumonia.

Three weeks prior to presentation, the patient was hospitalized for pancytopenia attributed to azathioprine-induced myelosuppression (hemoglobin, 6.1 g/dL [reference range, 13.5–18.0 g/dL]; hematocrit, 17.5% [reference range, 42%–52%]; white blood cell count, 1.66×10³/μL [reference range, 4.0–10.5×10³/μL]; platelet count, 146×10³/μL [reference range, 150–450×10³/μL]; absolute neutrophil count, 1.29×10³/μL [reference range, 1.4–6.5×10³/μL]). He was transferred to a skilled nursing facility after discharge and referred to dermatology for evaluation of the worsening pruritic rash.

At the current presentation, the patient denied close contact with anyone who had a similar rash at home or at the skilled nursing facility. Physical examination revealed diffuse erythroderma with yellow scale on the scalp, trunk, arms, and legs (Figure 1). The palms showed scattered 2- to 3-mm pustules. The mucosal surfaces did not have lesions. A punch biopsy of a pustule from the right arm revealed focal spongiosis, parakeratosis, and acanthosis, as well as a perivascular and interstitial mixed inflammatory infiltrate with lymphocytes and eosinophils. Organisms morphologically compatible with scabies were found in the stratum corneum (Figure 2). Another punch biopsy of a pustule from the right arm was performed for direct immunofluorescence (DIF) and was negative for immunoglobulin deposition. Mineral oil preparation from pustules on the palm was positive for mites.

The patient was treated with permethrin cream 5% and oral ivermectin 200 μg/kg on day 1 and day 10. The prednisone dosage was increased from 10 mg/d to 50 mg/d and tapered over 2 weeks to treat the symptomatic rash and GPA. He remains on maintenance rituximab for GPA, without recurrence of scabies.

Comment

Pathogenesis—As an obligate parasite, S scabiei spends its entire life cycle within the host. Impregnated female mites burrow into the epidermis after mating and lay eggs daily for 1 to 2 months. Eggs hatch 2 or 3 days later. Larvae then migrate to the skin surface; burrow into the stratum corneum, where they mature into adults; and then mate on the skin surface.^1,4

Clinical Presentation and Sequelae—Typically, scabies presents 2 to 6 weeks after initial exposure with generalized and intense itching and inflammatory pruritic papules on the finger webs, wrists, elbows, axillae, buttocks, umbilicus, genitalia, and areolae.¹ Burrows are specific for scabies but may not always be present. Often, there are nonspecific secondary lesions, including excoriations, dermatitis, and impetiginization.

Complications of scabies can be severe, with initial colonization and infection of the skin resulting in impetigo and cellulitis. Systematic sequelae from local skin infection include post-streptococcal glomerulonephritis, rheumatic fever, and sepsis. Mortality from sepsis in scabies can be high.^3,5

Classic Crusted Scabies and Other Variants—Crusted scabies presents with psoriasiform hyperkeratotic plaques involving the hands and feet with potential nail involvement that can become more generalized.¹ Alterations in CD4⁺ T-cell function have been implicated in the development of crusted scabies, in which an excessive helper T cell (T_H2) response is elicited against the ectoparasite, which may help explain the intense pruritus of scabies.⁶ Occasionally, iatrogenic immunosuppression contributes to development of crusted scabies,¹ as was the case with our patient. However, it is rare for crusted scabies to present with erythroderma.⁷

Other atypical presentations of scabies include a seborrheic dermatitis–like presentation in infants, nodular lesions in the groin and axillae in more chronic scabies, and vesicles or bullous lesions.¹

Diagnosis—Identification of mites, eggs, or feces is necessary for definitive diagnosis of scabies.⁸ These materials can be obtained through skin scrapings with mineral oil and observed under light microscopy or direct dermoscopy. Multiple scrapings on many lesions should be performed because failure to identify mites can be common and does not rule out scabies. Dermoscopic examination of active lesions under low power also can be helpful, given that identification of dark brown triangular structures can correspond to visualization of the pigmented anterior section of the mite.^9-11 A skin biopsy can help identify mites, but histopathology often shows a nonspecific hypersensitivity reaction.¹² Therefore, empiric treatment often is necessary.

Differential Diagnosis—The differential diagnosis of erythroderma is broad and includes a drug eruption; Sézary syndrome; and pre-existing skin diseases, including psoriasis, atopic dermatitis, pityriasis rubra pilaris, pemphigus foliaceus, and bullous pemphigoid. Histopathology is critical to differentiate these diagnoses. Bullous pemphigoid and pemphigus foliaceus are immunobullous diseases that typically are positive for immunoglobulin deposition on DIF. In rare cases, scabies also can present with bullae and positive DIF test results.¹³

Treatment—First-line treatment of crusted scabies in the United States is permethrin cream 5%, followed by oral ivermectin 200 μg/kg.^4,5,14,15 Other scabicides include topicals such as benzyl benzoate 10% to 25%; precipitated sulfur 2% to 10%; crotamiton 10%; malathion 0.5%; and lindane 1%.⁵ The association of neurotoxicity with lindane has considerably reduced the drug’s use.¹

During treatment of scabies, it is important to isolate patients to mitigate the possibility of spread.⁴ Pruritus can persist for a few weeks after completion of therapy.⁵ Patients should be closely monitored to ensure that this symptom is secondary to skin inflammation and not incomplete treatment.

Treatment of crusted scabies may require repeated treatments to decrease the notable mite burden as well as the associated crusting and scale. Adding a keratolytic such as 5% to 10% salicylic acid in petrolatum to the treatment regimen may be useful for breaking up thick scale.⁵

Immunosuppression—With numerous immunomodulatory drugs for treating autoimmunity comes an increased risk for iatrogenic immunosuppression that may contribute to the development of crusted scabies.¹⁶ In a number of autoimmune diseases such as rheumatoid arthritis,^17-19 psoriasis,^20,21 pemphigus vulgaris,²² systemic lupus erythematosus,²³ systemic sclerosis,^22,24 bullous pemphigoid,^25,26 and dermatomyositis,²⁷ patients have developed crusted scabies secondary to treatment-related immunosuppression. These immunosuppressive therapies include systemic steroids,^22-24,26-31 methotrexate,²³ infliximab,¹⁸ adalimumab,²¹ toclizumab,¹⁹ and etanercept.²⁰ In a case of drug-induced Stevens-Johnson syndrome, the patient developed crusted scabies during long-term use of oral steroids.²²

Patients with a malignancy who are being treated with chemotherapy also can develop crusted scabies.²⁸ Crusted scabies has even been associated with long-term topical steroid^32-34 and topical calcineurin inhibitor use.¹⁶

Iatrogenic immunosuppression in our patient resulted from treatment of GPA with azathioprine, an immunosuppressive drug that acts as an antagonist of the breakdown of purines, leading to inhibition of DNA, RNA, and protein synthesis.³⁵ On occasion, azathioprine can induce immunosuppression in the form of myelosuppression and resulting pancytopenia, as was the case with our patient.

Conclusion

Although scabies is designated as a neglected tropical disease by the World Health Organization, it still causes a notable burden worldwide, regardless of the economics. Our case highlights an unusual presentation of scabies as erythroderma in the setting of iatrogenic immunosuppression from azathioprine use. Dermatologists should consider crusted scabies in the differential diagnosis of erythroderma, especially in immunocompromised patients, to avoid delays in diagnosis and treatment. Immunosuppressive therapy is an important mainstay in the treatment of many conditions, but it is important to consider that these medications can place patients at an increased risk for rare opportunistic infections. Therefore, patients receiving such treatment should be closely monitored.

Scabies is caused by cutaneous ectoparasitic infection by the mite Sarcoptes scabiei var hominis. The infection is highly contagious via direct skin-to-skin contact or indirectly through infested bedding, clothing or fomites.^1,2 Scabies occurs at all ages, in all ethnic groups, and at all socioeconomic levels.¹ Analysis by the Global Burden of Disease estimates that 200 million individuals have been infected with scabies worldwide. The World Health Organization has declared scabies a neglected tropical disease.³

Crusted scabies is a severe and rare form of scabies, with hyperinfestation of thousands to millions of mites, and more commonly is associated with immunosuppressed states, including HIV and hematologic malignancies.^1,2,4 Crusted scabies has a high mortality rate due to sepsis when left untreated.^3,5

Occasionally, iatrogenic immunosuppression contributes to the development of crusted scabies.^1,2 Iatrogenic immunosuppression leading to crusted scabies most commonly occurs secondary to immunosuppression after bone marrow or solid organ transplantation.⁶ Less often, crusted scabies is caused by iatrogenic immunosuppression from other clinical scenarios.^1,2

We describe a patient with iatrogenic immunosuppression due to azathioprine-induced myelosuppression for the treatment of granulomatosis with polyangiitis (GPA) who developed crusted scabies that clinically presented as erythroderma. Crusted scabies should be included in the differential diagnosis of erythroderma, especially in the setting of iatrogenic immunosuppression, for timely and appropriate management.

Case Report

An 84-year-old man presented with worsening pruritus, erythema, and thick yellow scale that progressed to erythroderma over the last 2 weeks. He was diagnosed with GPA 6 months prior to presentation and was treated with azathioprine 150 mg/d, prednisone 10 mg/d, and sulfamethoxazole 800 mg plus trimethoprim 160 mg twice weekly for prophylaxis against Pneumocystis jirovecii pneumonia.

Three weeks prior to presentation, the patient was hospitalized for pancytopenia attributed to azathioprine-induced myelosuppression (hemoglobin, 6.1 g/dL [reference range, 13.5–18.0 g/dL]; hematocrit, 17.5% [reference range, 42%–52%]; white blood cell count, 1.66×10³/μL [reference range, 4.0–10.5×10³/μL]; platelet count, 146×10³/μL [reference range, 150–450×10³/μL]; absolute neutrophil count, 1.29×10³/μL [reference range, 1.4–6.5×10³/μL]). He was transferred to a skilled nursing facility after discharge and referred to dermatology for evaluation of the worsening pruritic rash.

At the current presentation, the patient denied close contact with anyone who had a similar rash at home or at the skilled nursing facility. Physical examination revealed diffuse erythroderma with yellow scale on the scalp, trunk, arms, and legs (Figure 1). The palms showed scattered 2- to 3-mm pustules. The mucosal surfaces did not have lesions. A punch biopsy of a pustule from the right arm revealed focal spongiosis, parakeratosis, and acanthosis, as well as a perivascular and interstitial mixed inflammatory infiltrate with lymphocytes and eosinophils. Organisms morphologically compatible with scabies were found in the stratum corneum (Figure 2). Another punch biopsy of a pustule from the right arm was performed for direct immunofluorescence (DIF) and was negative for immunoglobulin deposition. Mineral oil preparation from pustules on the palm was positive for mites.

The patient was treated with permethrin cream 5% and oral ivermectin 200 μg/kg on day 1 and day 10. The prednisone dosage was increased from 10 mg/d to 50 mg/d and tapered over 2 weeks to treat the symptomatic rash and GPA. He remains on maintenance rituximab for GPA, without recurrence of scabies.

Comment

Pathogenesis—As an obligate parasite, S scabiei spends its entire life cycle within the host. Impregnated female mites burrow into the epidermis after mating and lay eggs daily for 1 to 2 months. Eggs hatch 2 or 3 days later. Larvae then migrate to the skin surface; burrow into the stratum corneum, where they mature into adults; and then mate on the skin surface.^1,4

Clinical Presentation and Sequelae—Typically, scabies presents 2 to 6 weeks after initial exposure with generalized and intense itching and inflammatory pruritic papules on the finger webs, wrists, elbows, axillae, buttocks, umbilicus, genitalia, and areolae.¹ Burrows are specific for scabies but may not always be present. Often, there are nonspecific secondary lesions, including excoriations, dermatitis, and impetiginization.

Complications of scabies can be severe, with initial colonization and infection of the skin resulting in impetigo and cellulitis. Systematic sequelae from local skin infection include post-streptococcal glomerulonephritis, rheumatic fever, and sepsis. Mortality from sepsis in scabies can be high.^3,5

Classic Crusted Scabies and Other Variants—Crusted scabies presents with psoriasiform hyperkeratotic plaques involving the hands and feet with potential nail involvement that can become more generalized.¹ Alterations in CD4⁺ T-cell function have been implicated in the development of crusted scabies, in which an excessive helper T cell (T_H2) response is elicited against the ectoparasite, which may help explain the intense pruritus of scabies.⁶ Occasionally, iatrogenic immunosuppression contributes to development of crusted scabies,¹ as was the case with our patient. However, it is rare for crusted scabies to present with erythroderma.⁷

Other atypical presentations of scabies include a seborrheic dermatitis–like presentation in infants, nodular lesions in the groin and axillae in more chronic scabies, and vesicles or bullous lesions.¹

Diagnosis—Identification of mites, eggs, or feces is necessary for definitive diagnosis of scabies.⁸ These materials can be obtained through skin scrapings with mineral oil and observed under light microscopy or direct dermoscopy. Multiple scrapings on many lesions should be performed because failure to identify mites can be common and does not rule out scabies. Dermoscopic examination of active lesions under low power also can be helpful, given that identification of dark brown triangular structures can correspond to visualization of the pigmented anterior section of the mite.^9-11 A skin biopsy can help identify mites, but histopathology often shows a nonspecific hypersensitivity reaction.¹² Therefore, empiric treatment often is necessary.

Differential Diagnosis—The differential diagnosis of erythroderma is broad and includes a drug eruption; Sézary syndrome; and pre-existing skin diseases, including psoriasis, atopic dermatitis, pityriasis rubra pilaris, pemphigus foliaceus, and bullous pemphigoid. Histopathology is critical to differentiate these diagnoses. Bullous pemphigoid and pemphigus foliaceus are immunobullous diseases that typically are positive for immunoglobulin deposition on DIF. In rare cases, scabies also can present with bullae and positive DIF test results.¹³

Treatment—First-line treatment of crusted scabies in the United States is permethrin cream 5%, followed by oral ivermectin 200 μg/kg.^4,5,14,15 Other scabicides include topicals such as benzyl benzoate 10% to 25%; precipitated sulfur 2% to 10%; crotamiton 10%; malathion 0.5%; and lindane 1%.⁵ The association of neurotoxicity with lindane has considerably reduced the drug’s use.¹

During treatment of scabies, it is important to isolate patients to mitigate the possibility of spread.⁴ Pruritus can persist for a few weeks after completion of therapy.⁵ Patients should be closely monitored to ensure that this symptom is secondary to skin inflammation and not incomplete treatment.

Treatment of crusted scabies may require repeated treatments to decrease the notable mite burden as well as the associated crusting and scale. Adding a keratolytic such as 5% to 10% salicylic acid in petrolatum to the treatment regimen may be useful for breaking up thick scale.⁵

Immunosuppression—With numerous immunomodulatory drugs for treating autoimmunity comes an increased risk for iatrogenic immunosuppression that may contribute to the development of crusted scabies.¹⁶ In a number of autoimmune diseases such as rheumatoid arthritis,^17-19 psoriasis,^20,21 pemphigus vulgaris,²² systemic lupus erythematosus,²³ systemic sclerosis,^22,24 bullous pemphigoid,^25,26 and dermatomyositis,²⁷ patients have developed crusted scabies secondary to treatment-related immunosuppression. These immunosuppressive therapies include systemic steroids,^22-24,26-31 methotrexate,²³ infliximab,¹⁸ adalimumab,²¹ toclizumab,¹⁹ and etanercept.²⁰ In a case of drug-induced Stevens-Johnson syndrome, the patient developed crusted scabies during long-term use of oral steroids.²²

Patients with a malignancy who are being treated with chemotherapy also can develop crusted scabies.²⁸ Crusted scabies has even been associated with long-term topical steroid^32-34 and topical calcineurin inhibitor use.¹⁶

Iatrogenic immunosuppression in our patient resulted from treatment of GPA with azathioprine, an immunosuppressive drug that acts as an antagonist of the breakdown of purines, leading to inhibition of DNA, RNA, and protein synthesis.³⁵ On occasion, azathioprine can induce immunosuppression in the form of myelosuppression and resulting pancytopenia, as was the case with our patient.

Conclusion

Although scabies is designated as a neglected tropical disease by the World Health Organization, it still causes a notable burden worldwide, regardless of the economics. Our case highlights an unusual presentation of scabies as erythroderma in the setting of iatrogenic immunosuppression from azathioprine use. Dermatologists should consider crusted scabies in the differential diagnosis of erythroderma, especially in immunocompromised patients, to avoid delays in diagnosis and treatment. Immunosuppressive therapy is an important mainstay in the treatment of many conditions, but it is important to consider that these medications can place patients at an increased risk for rare opportunistic infections. Therefore, patients receiving such treatment should be closely monitored.

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

Even the plague wanted to visit Stonehenge

We’re about to blow your mind: The history you learned in school was often inaccurate. Shocking, we know, so we’ll give you a minute to process this incredible news.

Better? Good. Now, let’s look back at high school European history. The Black Death, specifically. The common narrative is that the Mongols, while besieging a Crimean city belonging to the Genoese, catapulted dead bodies infected with some mystery disease that turned out to be the plague. The Genoese then brought the plague back to Italy, and from there, we all know the rest of the story.

Ian Hodkinson, [email protected]

The Black Death was certainly extremely important to the development of modern Europe as we know it, but the history books gloss over the much longer history of the plague. Yersinia pestis did not suddenly appear unbidden in a Mongol war camp in 1347. The Black Death wasn’t even the first horrific, continent-wide pandemic caused by the plague; the Plague of Justinian 800 years earlier crippled the Byzantine Empire during an expansionist phase and killed anywhere between 15 million and 100 million.

Today, though, LOTME looks even deeper into history, nearly beyond even history itself, back into the depths of early Bronze Age northern Europe. Specifically, to two ancient burial sites in England, where researchers have identified three 4,000-year-old cases of Y. pestis, the first recorded incidence of the disease in Britain.

Two of the individuals, identified through analysis of dental pulp, were young children buried at a mass grave in Somerset, while the third, a middle-aged woman, was found in a ring cairn in Cumbria. These sites are hundreds of miles apart, yet carbon dating suggests all three people lived and died at roughly the same time. The strain found is very similar to other samples of plague found across central and western Europe starting around 3,000 BCE, suggesting a single, easily spread disease affecting a large area in a relatively small period of time. In other words, a pandemic. Even in these ancient times, the world was connected. Not even the island of Britain could escape.

Beyond that though, the research helps confirm the cyclical nature of the plague; over time, it loses its effectiveness and goes into hiding, only to mutate and come roaring back. This is a story with absolutely no relevance at all to the modern world. Nope, no plagues or pandemics going around right now, no viruses fading into the background in any way. What a ridiculous inference to make.
 

Uncovering the invisible with artificial intelligence

This week in “What Else Can AI Do?” new research shows that a computer program can reveal brain injury that couldn’t be seen before with typical MRI.

The hot new AI, birthed by researchers at New York University, could potentially be a game changer by linking repeated head impacts with tiny, structural changes in the brains of athletes who have not been diagnosed with a concussion. By using machine learning to train the AI, the researchers were, for the first time, able to distinguish the brain of athletes who played contact sports (football, soccer, lacrosse) from those participating in noncontact sports such as baseball, basketball, and cross-country.

Andrea Danti/Thinkstock

How did they do it? The investigators “designed statistical techniques that gave their computer program the ability to ‘learn’ how to predict exposure to repeated head impacts using mathematical models,” they explained in a written statement. Adding in data from the MRI scans of 81 male athletes with no known concussion diagnosis and the ability to identify unusual brain features between athletes with and without head trauma allowed the AI to predict results with accuracy even Miss Cleo would envy.

“This method may provide an important diagnostic tool not only for concussion, but also for detecting the damage that stems from subtler and more frequent head impacts,” said lead author Junbo Chen, an engineering doctoral candidate at NYU. That could make this new AI a valuable asset to science and medicine.

There are many things the human brain can do that AI can’t, and delegation could be one of them. Examining the data that represent the human brain in minute detail? Maybe we leave that to the machine.
 

Talk about your field promotions

If you’re a surgeon doing an amputation, the list of possible assistants pretty much starts and ends in only one place: Not the closest available janitor.

That may seem like an oddly obvious thing for us to say, but there’s at least one former Mainz (Germany) University Hospital physician who really needed to get this bit of advice before he attempted an unassisted toe amputation back in October of 2020. Yes, that does seem like kind of a long time ago for us to be reporting it now, but the details of the incident only just came to light a few days ago, thanks to German public broadcaster SWR.

Ente75/Wikipedia

Since it was just a toe, the surgeon thought he could perform the operation without any help. The toe, unfortunately, had other plans. The partially anesthetized patient got restless in the operating room, but with no actual trained nurse in the vicinity, the surgeon asked the closest available person – that would be the janitor – to lend a hand.

The surgical manager heard about these goings-on and got to the operating room too late to stop the procedure but soon enough to see the cleaning staffer “at the operating table with a bloody suction cup and a bloody compress in their hands,” SWR recently reported.

The incident was reported to the hospital’s medical director and the surgeon was fired, but since the patient experienced no complications not much fuss was made about it at the time.

Well, guess what? It’s toe-tally our job to make a fuss about these kinds of things. Or could it be that our job, much like the surgeon’s employment and the patient’s digit, is here toe-day and gone toe-morrow?

A new randomized trial offers rare insight into outcomes in adult tonsillectomy, a surgical procedure that’s commonly performed in the United States yet falling out of favor. Tonsillectomies are both clinically effective and cost-effective in adult patients with recurrent acute tonsillitis, a British team reports.

The researchers declined to weigh in on whether the procedure is actually better than nonsurgical management. Still, “here at last, we have a substantial piece of scientific evidence which shows that, compared with nonsurgical management, removal of tonsils has a significant impact on the number of sore throat days and on the cost of managing sore throat disease in adults,” said study lead author Janet A. Wilson, MBChB, MD, an emerita professor of otolaryngology at Newcastle University (England), in an interview.

The study was published in The Lancet.

Tonsillectomies have become much less common over the past several decades as questions have arisen about their value. In the United States, the number of procedures performed each year plunged from a high of 1.4 million in 1959 to an estimated 286,000 tonsillectomies performed in children under 15 and 120,000 in people aged 15 in 2010.

It’s harder for adults to tolerate tonsillectomies than children, Dr. Wilson said. In children, surgeons can easily remove tonsils by scraping them off the throat’s side walls. But, she said, “an adult tonsillectomy is more akin to taking off the skin of an unripe orange, so it’s harder work for the surgeon and more traumatizing for the wall of the adult patient’s pharynx. We can only assume that this greater amount of fibrous tissue reflects the cumulative effect of infections over a period of years.”

While tonsillectomies are still performed hundreds of times a day in adults in the United States, a 2014 Cochrane Library review found there’s “insufficient information “to support them versus nonsurgical care as treatments to reduce sore throats.”

For the new multicenter, open-label, randomized study, researchers randomly assigned patients aged 16 and older with recurrent acute tonsillitis to immediate tonsillectomy or nonsurgical management, which Dr. Wilson said can include cold fluids, honey, analgesics/anti-inflammatories. and anesthetic throat lozenges. The study was conducted between 2015 and 2018.

Ultimately, there were 224 and 204 patients, respectively, in the two groups (average age = 23, [19-30], 78% female, 90% White).

Patients who underwent tonsillectomies versus nonsurgical treatment had fewer sore throats over 2 years (median 23 days [IQR 11-46 days] vs. 30 days [14-65 days]) with an incident rate ratio of 0.53 (95% confidence interval, 0.43-0.65, P < 0.0001) after adjustment for clinic site and baseline severity.

The study also shows that “adults who have severe recurrent throat infections with a frequency of seven episodes within 1 year, five or more for 2 consecutive years, or three or more in 3 consecutive years will suffer fewer days of sore throat in the 2 years following tonsillectomy than if they had kept their tonsils,” Dr. Wilson said.

The study doesn’t examine longer-term consequences. A 2018 study of children linked tonsillectomies to “significantly increased relative risk of later respiratory, allergic, and infectious diseases.”

In the new study, nearly 4 in 10 (39%) of the tonsillectomy patients had adverse events linked to the surgeries, and bleeding (19%) was the most common adverse effect. The researchers also estimated that “tonsillectomy has a high probability of being considered cost-effective.”

“Whichever way the results were analyzed and confounding variables allowed for, the result always seems to be the same: Tonsillectomy applied using current qualifying criteria was a worthwhile procedure,” Dr. Wilson said.

Dr. Wilson noted that tonsillectomy patients will suffer a persistent sore throat after surgery, “about the same as a bad episode of tonsillitis.” And she said patients will need to adjust their diet for a few days and take 1-2 weeks off work.

In an interview, internal medicine physician Noel Deep, MD, of Antigo, Wisc., said antibiotics are a common treatment for tonsillitis in primary care clinics. According to him, the United States doesn’t have guidelines for tonsillectomies in adults. He believes they can be considered if tonsillitis keeps recurring three to five times a year and disrupts quality of life.

Dr. Deep said the new study “reinforces the benefit of tonsillectomies. Several studies from Germany, Sweden, Finland, and the United Kingdom have demonstrated benefits of tonsillectomies, but they were only for short periods of less than a year and lacked long-term data.”

He noted that “there is no clear evidence as to when to recommend tonsillectomies.” Clinicians should talk to patients about the potential that tonsillectomies will reduce sore throat episodes and cost the patient less in the long run, he said. It’s also important, he said, to make sure tonsillitis is bacterial before prescribing antibiotics.

The United Kingdom’s National Institute for Health Research funded the study. Dr. Wilson disclosed support for meetings/travel from ENT Scotland, and the other authors report various disclosures, including grants and contracts. Dr. Deep serves on the editorial advisory board of Internal Medicine News and is chair of the American Medical Association Council on Science and Public Health.

[email protected]

A new randomized trial offers rare insight into outcomes in adult tonsillectomy, a surgical procedure that’s commonly performed in the United States yet falling out of favor. Tonsillectomies are both clinically effective and cost-effective in adult patients with recurrent acute tonsillitis, a British team reports.

The researchers declined to weigh in on whether the procedure is actually better than nonsurgical management. Still, “here at last, we have a substantial piece of scientific evidence which shows that, compared with nonsurgical management, removal of tonsils has a significant impact on the number of sore throat days and on the cost of managing sore throat disease in adults,” said study lead author Janet A. Wilson, MBChB, MD, an emerita professor of otolaryngology at Newcastle University (England), in an interview.

The study was published in The Lancet.

Tonsillectomies have become much less common over the past several decades as questions have arisen about their value. In the United States, the number of procedures performed each year plunged from a high of 1.4 million in 1959 to an estimated 286,000 tonsillectomies performed in children under 15 and 120,000 in people aged 15 in 2010.

It’s harder for adults to tolerate tonsillectomies than children, Dr. Wilson said. In children, surgeons can easily remove tonsils by scraping them off the throat’s side walls. But, she said, “an adult tonsillectomy is more akin to taking off the skin of an unripe orange, so it’s harder work for the surgeon and more traumatizing for the wall of the adult patient’s pharynx. We can only assume that this greater amount of fibrous tissue reflects the cumulative effect of infections over a period of years.”

While tonsillectomies are still performed hundreds of times a day in adults in the United States, a 2014 Cochrane Library review found there’s “insufficient information “to support them versus nonsurgical care as treatments to reduce sore throats.”

For the new multicenter, open-label, randomized study, researchers randomly assigned patients aged 16 and older with recurrent acute tonsillitis to immediate tonsillectomy or nonsurgical management, which Dr. Wilson said can include cold fluids, honey, analgesics/anti-inflammatories. and anesthetic throat lozenges. The study was conducted between 2015 and 2018.

Ultimately, there were 224 and 204 patients, respectively, in the two groups (average age = 23, [19-30], 78% female, 90% White).

Patients who underwent tonsillectomies versus nonsurgical treatment had fewer sore throats over 2 years (median 23 days [IQR 11-46 days] vs. 30 days [14-65 days]) with an incident rate ratio of 0.53 (95% confidence interval, 0.43-0.65, P < 0.0001) after adjustment for clinic site and baseline severity.

The study also shows that “adults who have severe recurrent throat infections with a frequency of seven episodes within 1 year, five or more for 2 consecutive years, or three or more in 3 consecutive years will suffer fewer days of sore throat in the 2 years following tonsillectomy than if they had kept their tonsils,” Dr. Wilson said.

The study doesn’t examine longer-term consequences. A 2018 study of children linked tonsillectomies to “significantly increased relative risk of later respiratory, allergic, and infectious diseases.”

In the new study, nearly 4 in 10 (39%) of the tonsillectomy patients had adverse events linked to the surgeries, and bleeding (19%) was the most common adverse effect. The researchers also estimated that “tonsillectomy has a high probability of being considered cost-effective.”

“Whichever way the results were analyzed and confounding variables allowed for, the result always seems to be the same: Tonsillectomy applied using current qualifying criteria was a worthwhile procedure,” Dr. Wilson said.

Dr. Wilson noted that tonsillectomy patients will suffer a persistent sore throat after surgery, “about the same as a bad episode of tonsillitis.” And she said patients will need to adjust their diet for a few days and take 1-2 weeks off work.

In an interview, internal medicine physician Noel Deep, MD, of Antigo, Wisc., said antibiotics are a common treatment for tonsillitis in primary care clinics. According to him, the United States doesn’t have guidelines for tonsillectomies in adults. He believes they can be considered if tonsillitis keeps recurring three to five times a year and disrupts quality of life.

Dr. Deep said the new study “reinforces the benefit of tonsillectomies. Several studies from Germany, Sweden, Finland, and the United Kingdom have demonstrated benefits of tonsillectomies, but they were only for short periods of less than a year and lacked long-term data.”

He noted that “there is no clear evidence as to when to recommend tonsillectomies.” Clinicians should talk to patients about the potential that tonsillectomies will reduce sore throat episodes and cost the patient less in the long run, he said. It’s also important, he said, to make sure tonsillitis is bacterial before prescribing antibiotics.

The United Kingdom’s National Institute for Health Research funded the study. Dr. Wilson disclosed support for meetings/travel from ENT Scotland, and the other authors report various disclosures, including grants and contracts. Dr. Deep serves on the editorial advisory board of Internal Medicine News and is chair of the American Medical Association Council on Science and Public Health.

[email protected]

A new randomized trial offers rare insight into outcomes in adult tonsillectomy, a surgical procedure that’s commonly performed in the United States yet falling out of favor. Tonsillectomies are both clinically effective and cost-effective in adult patients with recurrent acute tonsillitis, a British team reports.

The researchers declined to weigh in on whether the procedure is actually better than nonsurgical management. Still, “here at last, we have a substantial piece of scientific evidence which shows that, compared with nonsurgical management, removal of tonsils has a significant impact on the number of sore throat days and on the cost of managing sore throat disease in adults,” said study lead author Janet A. Wilson, MBChB, MD, an emerita professor of otolaryngology at Newcastle University (England), in an interview.

The study was published in The Lancet.

Tonsillectomies have become much less common over the past several decades as questions have arisen about their value. In the United States, the number of procedures performed each year plunged from a high of 1.4 million in 1959 to an estimated 286,000 tonsillectomies performed in children under 15 and 120,000 in people aged 15 in 2010.

It’s harder for adults to tolerate tonsillectomies than children, Dr. Wilson said. In children, surgeons can easily remove tonsils by scraping them off the throat’s side walls. But, she said, “an adult tonsillectomy is more akin to taking off the skin of an unripe orange, so it’s harder work for the surgeon and more traumatizing for the wall of the adult patient’s pharynx. We can only assume that this greater amount of fibrous tissue reflects the cumulative effect of infections over a period of years.”

While tonsillectomies are still performed hundreds of times a day in adults in the United States, a 2014 Cochrane Library review found there’s “insufficient information “to support them versus nonsurgical care as treatments to reduce sore throats.”

For the new multicenter, open-label, randomized study, researchers randomly assigned patients aged 16 and older with recurrent acute tonsillitis to immediate tonsillectomy or nonsurgical management, which Dr. Wilson said can include cold fluids, honey, analgesics/anti-inflammatories. and anesthetic throat lozenges. The study was conducted between 2015 and 2018.

Ultimately, there were 224 and 204 patients, respectively, in the two groups (average age = 23, [19-30], 78% female, 90% White).

Patients who underwent tonsillectomies versus nonsurgical treatment had fewer sore throats over 2 years (median 23 days [IQR 11-46 days] vs. 30 days [14-65 days]) with an incident rate ratio of 0.53 (95% confidence interval, 0.43-0.65, P < 0.0001) after adjustment for clinic site and baseline severity.

The study also shows that “adults who have severe recurrent throat infections with a frequency of seven episodes within 1 year, five or more for 2 consecutive years, or three or more in 3 consecutive years will suffer fewer days of sore throat in the 2 years following tonsillectomy than if they had kept their tonsils,” Dr. Wilson said.

The study doesn’t examine longer-term consequences. A 2018 study of children linked tonsillectomies to “significantly increased relative risk of later respiratory, allergic, and infectious diseases.”

In the new study, nearly 4 in 10 (39%) of the tonsillectomy patients had adverse events linked to the surgeries, and bleeding (19%) was the most common adverse effect. The researchers also estimated that “tonsillectomy has a high probability of being considered cost-effective.”

“Whichever way the results were analyzed and confounding variables allowed for, the result always seems to be the same: Tonsillectomy applied using current qualifying criteria was a worthwhile procedure,” Dr. Wilson said.

Dr. Wilson noted that tonsillectomy patients will suffer a persistent sore throat after surgery, “about the same as a bad episode of tonsillitis.” And she said patients will need to adjust their diet for a few days and take 1-2 weeks off work.

In an interview, internal medicine physician Noel Deep, MD, of Antigo, Wisc., said antibiotics are a common treatment for tonsillitis in primary care clinics. According to him, the United States doesn’t have guidelines for tonsillectomies in adults. He believes they can be considered if tonsillitis keeps recurring three to five times a year and disrupts quality of life.

Dr. Deep said the new study “reinforces the benefit of tonsillectomies. Several studies from Germany, Sweden, Finland, and the United Kingdom have demonstrated benefits of tonsillectomies, but they were only for short periods of less than a year and lacked long-term data.”

He noted that “there is no clear evidence as to when to recommend tonsillectomies.” Clinicians should talk to patients about the potential that tonsillectomies will reduce sore throat episodes and cost the patient less in the long run, he said. It’s also important, he said, to make sure tonsillitis is bacterial before prescribing antibiotics.

The United Kingdom’s National Institute for Health Research funded the study. Dr. Wilson disclosed support for meetings/travel from ENT Scotland, and the other authors report various disclosures, including grants and contracts. Dr. Deep serves on the editorial advisory board of Internal Medicine News and is chair of the American Medical Association Council on Science and Public Health.

[email protected]

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

A resurgence of mpox this summer could be larger than last year’s caseload, the Centers for Disease Control and Prevention said in a warning to public health officials this week.

“The outbreak is not over,” the CDC alert stated, noting that springtime and summertime gatherings and festivals could lead to renewed virus spread. A new cluster of 13 cases is being investigated in Chicago, all among men, and four among people who recently traveled to New York City, New Orleans, or Mexico. 

Mpox, formerly called monkeypox, is a virus that causes a rash and sometimes flulike symptoms. It is most often transmitted through sexual contact, but it can also be spread in nonsexual ways that involve contact with skin lesions or with saliva or upper respiratory secretions like snot or mucus, the CDC says. Most cases in the United States have been among gay or bisexual men, men who have sex with men, and transgender people.

Last year, the U.S. government declared mpox a public health emergency as cases peaked at 460 per day in August, infecting more than 30,000 people and killing 42 people. Public health officials worked to quickly distribute vaccinations to people at high risk for contracting the virus. The CDC says 23% of people most at risk of getting mpox have been vaccinated.

The agency advises that people be vaccinated for mpox based on their potential exposure risk. Vaccination does not necessarily prevent infection but can lessen the severity of symptoms. Nine of the men who were recently infected in Chicago were fully vaccinated.

“It’s important to remember that vaccines, while incredibly helpful, are not our only way to reduce the risk of contracting mpox,” Richard Silvera, MD, MPH, of the department of infectious diseases at Icahn School of Medicine at Mount Sinai, New York, told ABC News. 

Other ways to reduce risk are “things like avoiding social and sexual contact if you have new skin lesions and asking your intimate contacts if they are experiencing symptoms or new skin changes,” Dr. Silvera said.

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

A resurgence of mpox this summer could be larger than last year’s caseload, the Centers for Disease Control and Prevention said in a warning to public health officials this week.

“The outbreak is not over,” the CDC alert stated, noting that springtime and summertime gatherings and festivals could lead to renewed virus spread. A new cluster of 13 cases is being investigated in Chicago, all among men, and four among people who recently traveled to New York City, New Orleans, or Mexico. 

Mpox, formerly called monkeypox, is a virus that causes a rash and sometimes flulike symptoms. It is most often transmitted through sexual contact, but it can also be spread in nonsexual ways that involve contact with skin lesions or with saliva or upper respiratory secretions like snot or mucus, the CDC says. Most cases in the United States have been among gay or bisexual men, men who have sex with men, and transgender people.

Last year, the U.S. government declared mpox a public health emergency as cases peaked at 460 per day in August, infecting more than 30,000 people and killing 42 people. Public health officials worked to quickly distribute vaccinations to people at high risk for contracting the virus. The CDC says 23% of people most at risk of getting mpox have been vaccinated.

The agency advises that people be vaccinated for mpox based on their potential exposure risk. Vaccination does not necessarily prevent infection but can lessen the severity of symptoms. Nine of the men who were recently infected in Chicago were fully vaccinated.

“It’s important to remember that vaccines, while incredibly helpful, are not our only way to reduce the risk of contracting mpox,” Richard Silvera, MD, MPH, of the department of infectious diseases at Icahn School of Medicine at Mount Sinai, New York, told ABC News. 

Other ways to reduce risk are “things like avoiding social and sexual contact if you have new skin lesions and asking your intimate contacts if they are experiencing symptoms or new skin changes,” Dr. Silvera said.

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

A resurgence of mpox this summer could be larger than last year’s caseload, the Centers for Disease Control and Prevention said in a warning to public health officials this week.

“The outbreak is not over,” the CDC alert stated, noting that springtime and summertime gatherings and festivals could lead to renewed virus spread. A new cluster of 13 cases is being investigated in Chicago, all among men, and four among people who recently traveled to New York City, New Orleans, or Mexico. 

Mpox, formerly called monkeypox, is a virus that causes a rash and sometimes flulike symptoms. It is most often transmitted through sexual contact, but it can also be spread in nonsexual ways that involve contact with skin lesions or with saliva or upper respiratory secretions like snot or mucus, the CDC says. Most cases in the United States have been among gay or bisexual men, men who have sex with men, and transgender people.

Last year, the U.S. government declared mpox a public health emergency as cases peaked at 460 per day in August, infecting more than 30,000 people and killing 42 people. Public health officials worked to quickly distribute vaccinations to people at high risk for contracting the virus. The CDC says 23% of people most at risk of getting mpox have been vaccinated.

The agency advises that people be vaccinated for mpox based on their potential exposure risk. Vaccination does not necessarily prevent infection but can lessen the severity of symptoms. Nine of the men who were recently infected in Chicago were fully vaccinated.

“It’s important to remember that vaccines, while incredibly helpful, are not our only way to reduce the risk of contracting mpox,” Richard Silvera, MD, MPH, of the department of infectious diseases at Icahn School of Medicine at Mount Sinai, New York, told ABC News. 

Other ways to reduce risk are “things like avoiding social and sexual contact if you have new skin lesions and asking your intimate contacts if they are experiencing symptoms or new skin changes,” Dr. Silvera said.

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

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.

Fastest peptide north, south, east, aaaaand west of the Pecos

Bacterial infections are supposed to be simple. You get infected, you get an antibiotic to treat it. Easy. Some bacteria, though, don’t play by the rules. Those antibiotics may kill 99.9% of germs, but what about the 0.1% that gets left behind? With their fallen comrades out of the way, the accidentally drug resistant species are free to inherit the Earth.

Antibiotic resistance is thus a major concern for the medical community. Naturally, anything that prevents doctors from successfully curing sick people is a priority. Unless you’re a major pharmaceutical company that has been loath to develop new drugs that can beat antibiotic-resistant bacteria. Blah blah, time and money, blah blah, long time between development and market application, blah blah, no profit. We all know the story with pharmaceutical companies.

Ilana Camargo

Research from other sources has continued, however, and Brazilian scientists recently published research involving a peptide known as plantaricin 149. This peptide, derived from the bacterium Lactobacillus plantarum, has been known for nearly 30 years to have antibacterial properties. Pln149 in its natural state, though, is not particularly efficient at bacteria-killing. Fortunately, we have science and technology on our side.

The researchers synthesized 20 analogs of Pln149, of which Pln149-PEP20 had the best results. The elegantly named compound is less than half the size of the original peptide, less toxic, and far better at killing any and all drug-resistant bacteria the researchers threw at it. How much better? Pln149-PEP20 started killing bacteria less than an hour after being introduced in lab trials.

The research is just in its early days – just because something is less toxic doesn’t necessarily mean you want to go and help yourself to it – but we can only hope that those lovely pharmaceutical companies deign to look down upon us and actually develop a drug utilizing Pln149-PEP20 to, you know, actually help sick people, instead of trying to build monopolies or avoiding paying billions in taxes. Yeah, we couldn’t keep a straight face through that last sentence either.
 

Speed healing: The wavy wound gets the swirl

Did you know that wavy wounds heal faster than straight wounds? Well, we didn’t, but apparently quite a few people did, because somebody has been trying to figure out why wavy wounds heal faster than straight ones. Do the surgeons know about this? How about you dermatologists? Wavy over straight? We’re the media. We’re supposed to report this kind of stuff. Maybe hit us with a tweet next time you do something important, or push a TikTok our way, okay?

You could be more like the investigators at Nanyang Technological University in Singapore, who figured out the why and then released a statement about it.

NTU Singapore

They created synthetic wounds – some straight, some wavy – in micropatterned hydrogel substrates that mimicked human skin. Then they used an advanced optical technique known as particle image velocimetry to measure fluid flow and learn how cells moved to close the wound gaps.

The wavy wounds “induced more complex collective cell movements, such as a swirly, vortex-like motion,” according to the written statement from NTU Singapore. In the straight wounds, cell movements paralleled the wound front, “moving in straight lines like a marching band,” they pointed out, unlike some researchers who never call us unless they need money.

Complex epithelial cell movements are better, it turns out. Over an observation period of 64 hours the NTU team found that the healing efficiency of wavy gaps – measured by the area covered by the cells over time – is nearly five times faster than straight gaps.

The complex motion “enabled cells to quickly connect with similar cells on the opposite site of the wound edge, forming a bridge and closing the wavy wound gaps faster than straight gaps,” explained lead author Xu Hongmei, a doctoral student at NTU’s School of Mechanical and Aerospace Engineering, who seems to have time to toss out a tumblr or two to keep the press informed.

As for the rest of you, would it kill you to pick up a phone once in a while? Maybe let a journalist know that you’re still alive? We have feelings too, you know, and we worry.
 

A little Jekyll, a little Hyde, and a little shop of horrors

More “Little Shop of Horrors” references are coming, so be prepared.

We begin with Triphyophyllum peltatum. This woody vine is of great interest to medical and pharmaceutical researchers because its constituents have shown promise against pancreatic cancer and leukemia cells, among others, along with the pathogens that cause malaria and other diseases. There is another side, however. T. peltatum also has a tendency to turn into a realistic Audrey II when deprived.

No, of course they’re not craving human flesh, but it does become … carnivorous in its appetite.

T. peltatum, native to the West African tropics and not found in a New York florist shop, has the unique ability to change its diet and development based on the environmental circumstances. For some unknown reason, the leaves would develop adhesive traps in the form of sticky drops that capture insect prey. The plant is notoriously hard to grow, however, so no one could study the transformation under lab conditions. Until now.

Traud Winkelmann/University of Hannover

A group of German scientists “exposed the plant to different stress factors, including deficiencies of various nutrients, and studied how it responded to each,” said Dr. Traud Winkelmann of Leibniz University Hannover. “Only in one case were we able to observe the formation of traps: in the case of a lack of phosphorus.”

Well, there you have it: phosphorus. We need it for healthy bones and teeth, which this plant doesn’t have to worry about, unlike its Tony Award–nominated counterpart. The investigators hope that their findings could lead to “future molecular analyses that will help understand the origins of carnivory,” but we’re guessing that a certain singing alien species will be left out of that research.