Infectious Diseases

In the early weeks and months of the COVID-19 pandemic, many people were trying to avoid the coronavirus by staying away from emergency rooms and medical offices. But how many people is “many”?

Turns out almost 41% of Americans delayed or avoided some form of medical care because of concerns about COVID-19, according to the results of a survey conducted June 24-30 by commercial survey company Qualtrics.

More specifically, the avoidance looks like this: 31.5% of the 4,975 adult respondents had avoided routine care and 12.0% had avoided urgent or emergency care, Mark E. Czeisler and associates said in the Morbidity and Mortality Weekly Report. The two categories were not mutually exclusive since respondents could select both routine care and urgent/emergency care.

There were, however, a number of significant disparities hidden among those numbers for the overall population. Blacks and Hispanics, with respective prevalences of 23.3% and 24.6%, were significantly more likely to delay or avoid urgent/emergency care than were Whites (6.7%), said Mr. Czeisler, a graduate student at Monash University, Melbourne, and associates.

Those differences “are especially concerning given increased COVID-19–associated mortality among Black adults and Hispanic adults,” they noted, adding that “age-adjusted COVID-19 hospitalization rates are approximately five times higher among Black persons and four times higher among Hispanic persons than” among Whites.

Other significant disparities in urgent/emergency care avoidance included the following:

• Unpaid caregivers for adults (29.8%) vs. noncaregivers (5.4%).
• Adults with two or more underlying conditions (22.7%) vs. those without such conditions (8.2%).
• Those with a disability (22.8%) vs. those without (8.9%).
• Those with health insurance (12.4%) vs. those without (7.8%).

The highest prevalence for all types of COVID-19–related delay and avoidance came from the adult caregivers (64.3%), followed by those with a disability (60.3%) and adults aged 18-24 years (57.2%). The lowest prevalence numbers were for adults with health insurance (24.8%) and those who were not caregivers for adults (32.2%), Mr. Czeisler and associates reported.

These reports of delayed and avoided care “might reflect adherence to community mitigation efforts such as stay-at-home orders, temporary closures of health facilities, or additional factors. However, if routine care avoidance were to be sustained, adults could miss opportunities for management of chronic conditions, receipt of routine vaccinations, or early detection of new conditions, which might worsen outcomes,” they wrote.

[email protected]

SOURCE: Czeisler ME et al. MMWR. 2020 Sep 11;69(36):1250-7.

In the early weeks and months of the COVID-19 pandemic, many people were trying to avoid the coronavirus by staying away from emergency rooms and medical offices. But how many people is “many”?

Turns out almost 41% of Americans delayed or avoided some form of medical care because of concerns about COVID-19, according to the results of a survey conducted June 24-30 by commercial survey company Qualtrics.

More specifically, the avoidance looks like this: 31.5% of the 4,975 adult respondents had avoided routine care and 12.0% had avoided urgent or emergency care, Mark E. Czeisler and associates said in the Morbidity and Mortality Weekly Report. The two categories were not mutually exclusive since respondents could select both routine care and urgent/emergency care.

There were, however, a number of significant disparities hidden among those numbers for the overall population. Blacks and Hispanics, with respective prevalences of 23.3% and 24.6%, were significantly more likely to delay or avoid urgent/emergency care than were Whites (6.7%), said Mr. Czeisler, a graduate student at Monash University, Melbourne, and associates.

Those differences “are especially concerning given increased COVID-19–associated mortality among Black adults and Hispanic adults,” they noted, adding that “age-adjusted COVID-19 hospitalization rates are approximately five times higher among Black persons and four times higher among Hispanic persons than” among Whites.

Other significant disparities in urgent/emergency care avoidance included the following:

• Unpaid caregivers for adults (29.8%) vs. noncaregivers (5.4%).
• Adults with two or more underlying conditions (22.7%) vs. those without such conditions (8.2%).
• Those with a disability (22.8%) vs. those without (8.9%).
• Those with health insurance (12.4%) vs. those without (7.8%).

The highest prevalence for all types of COVID-19–related delay and avoidance came from the adult caregivers (64.3%), followed by those with a disability (60.3%) and adults aged 18-24 years (57.2%). The lowest prevalence numbers were for adults with health insurance (24.8%) and those who were not caregivers for adults (32.2%), Mr. Czeisler and associates reported.

These reports of delayed and avoided care “might reflect adherence to community mitigation efforts such as stay-at-home orders, temporary closures of health facilities, or additional factors. However, if routine care avoidance were to be sustained, adults could miss opportunities for management of chronic conditions, receipt of routine vaccinations, or early detection of new conditions, which might worsen outcomes,” they wrote.

[email protected]

SOURCE: Czeisler ME et al. MMWR. 2020 Sep 11;69(36):1250-7.

In the early weeks and months of the COVID-19 pandemic, many people were trying to avoid the coronavirus by staying away from emergency rooms and medical offices. But how many people is “many”?

Turns out almost 41% of Americans delayed or avoided some form of medical care because of concerns about COVID-19, according to the results of a survey conducted June 24-30 by commercial survey company Qualtrics.

More specifically, the avoidance looks like this: 31.5% of the 4,975 adult respondents had avoided routine care and 12.0% had avoided urgent or emergency care, Mark E. Czeisler and associates said in the Morbidity and Mortality Weekly Report. The two categories were not mutually exclusive since respondents could select both routine care and urgent/emergency care.

There were, however, a number of significant disparities hidden among those numbers for the overall population. Blacks and Hispanics, with respective prevalences of 23.3% and 24.6%, were significantly more likely to delay or avoid urgent/emergency care than were Whites (6.7%), said Mr. Czeisler, a graduate student at Monash University, Melbourne, and associates.

Those differences “are especially concerning given increased COVID-19–associated mortality among Black adults and Hispanic adults,” they noted, adding that “age-adjusted COVID-19 hospitalization rates are approximately five times higher among Black persons and four times higher among Hispanic persons than” among Whites.

Other significant disparities in urgent/emergency care avoidance included the following:

• Unpaid caregivers for adults (29.8%) vs. noncaregivers (5.4%).
• Adults with two or more underlying conditions (22.7%) vs. those without such conditions (8.2%).
• Those with a disability (22.8%) vs. those without (8.9%).
• Those with health insurance (12.4%) vs. those without (7.8%).

The highest prevalence for all types of COVID-19–related delay and avoidance came from the adult caregivers (64.3%), followed by those with a disability (60.3%) and adults aged 18-24 years (57.2%). The lowest prevalence numbers were for adults with health insurance (24.8%) and those who were not caregivers for adults (32.2%), Mr. Czeisler and associates reported.

These reports of delayed and avoided care “might reflect adherence to community mitigation efforts such as stay-at-home orders, temporary closures of health facilities, or additional factors. However, if routine care avoidance were to be sustained, adults could miss opportunities for management of chronic conditions, receipt of routine vaccinations, or early detection of new conditions, which might worsen outcomes,” they wrote.

[email protected]

SOURCE: Czeisler ME et al. MMWR. 2020 Sep 11;69(36):1250-7.

Coronavirus disease 2019 (COVID-19) has spread across all 7 continents, including 185 countries, and infected more than 21.9 million individuals worldwide as of August 18, 2020, according to the Johns Hopkins Coronavirus Resource Center. It has strained our health care system and affected all specialties, including dermatology. Dermatologists have taken important safety measures by canceling/deferring elective and nonemergency procedures and diagnosing/treating patients via telemedicine. Many residents and attending dermatologists have volunteered to care for COVID-19 inpatients and donated personal protective equipment (PPE) to hospitals reporting shortages.¹ As we prepare to treat increasing numbers of in-office patients, there will be a critical need for PPE. We highlight the use of 3-dimensional (3D) imaging and printing technologies as it applies to the dermatology outpatient setting.

N95 masks are necessary during the COVID-19 pandemic because they effectively filter at least 95% of 0.3-μm airborne particles and provide adequate face seals.¹ 3-Dimensional imaging integrated with 3D printers can be used to scan precise facial parameters (eg, jawline, nose) and account for facial hair density and length to produce comfortable tailored N95 masks and face seals.^1,2 3-Dimensional printing utilizes robotics and computer-aided design systems to layer and deposit biomaterials, thereby creating cost-effective, customizable, mechanically stable, and biocompatible constructs.^1,3 An ideal 3D-printed N95 mask would be printed via fused deposition modeling, consisting of a combination of lightweight and fatigue-resistant biomaterials, including electrostatic nonwoven polypropylene and styrene-(ethylene-butylene)-styrene.^1,4 The resulting masks, made from industrial-grade raw materials, are practical alternatives for dermatology practices with insufficient supplies.

Face shields offer an additional layer of safety for the face and mucosae and also may provide longevity for N95 masks. Using synthetic polymers such as polycarbonate and polyethylene, 3D printers can be used to construct face shields via fused deposition modeling.¹ These face shields may be worn over N95 masks and then can be sanitized and reused.

Mohs surgeons and staff may be at particularly high risk for COVID-19 infection due to their close proximity to the face during surgery, use of cautery, and prolonged time spent with patients while taking layers and suturing. Multispectral optoacoustic tomography is a noninvasive imaging tool that can map skin tumors via optical contrast with accuracy comparable to histologic measurements.⁵ 3-Dimensional facial imaging and printing can be used to calculate tumor surface area for customized masks, leaving sufficient skin for excision and reconstruction. Patient face coverings would cover the nose and mouth, only expose relevant areas near the excision site, and include adjustable/removable ear loops for tumors localized to the ears. A schematic of how 3D technologies can be applied for Mohs micrographic surgery is provided in the Figure.

Coronavirus disease 2019 (COVID-19) has spread across all 7 continents, including 185 countries, and infected more than 21.9 million individuals worldwide as of August 18, 2020, according to the Johns Hopkins Coronavirus Resource Center. It has strained our health care system and affected all specialties, including dermatology. Dermatologists have taken important safety measures by canceling/deferring elective and nonemergency procedures and diagnosing/treating patients via telemedicine. Many residents and attending dermatologists have volunteered to care for COVID-19 inpatients and donated personal protective equipment (PPE) to hospitals reporting shortages.¹ As we prepare to treat increasing numbers of in-office patients, there will be a critical need for PPE. We highlight the use of 3-dimensional (3D) imaging and printing technologies as it applies to the dermatology outpatient setting.

N95 masks are necessary during the COVID-19 pandemic because they effectively filter at least 95% of 0.3-μm airborne particles and provide adequate face seals.¹ 3-Dimensional imaging integrated with 3D printers can be used to scan precise facial parameters (eg, jawline, nose) and account for facial hair density and length to produce comfortable tailored N95 masks and face seals.^1,2 3-Dimensional printing utilizes robotics and computer-aided design systems to layer and deposit biomaterials, thereby creating cost-effective, customizable, mechanically stable, and biocompatible constructs.^1,3 An ideal 3D-printed N95 mask would be printed via fused deposition modeling, consisting of a combination of lightweight and fatigue-resistant biomaterials, including electrostatic nonwoven polypropylene and styrene-(ethylene-butylene)-styrene.^1,4 The resulting masks, made from industrial-grade raw materials, are practical alternatives for dermatology practices with insufficient supplies.

Face shields offer an additional layer of safety for the face and mucosae and also may provide longevity for N95 masks. Using synthetic polymers such as polycarbonate and polyethylene, 3D printers can be used to construct face shields via fused deposition modeling.¹ These face shields may be worn over N95 masks and then can be sanitized and reused.

Mohs surgeons and staff may be at particularly high risk for COVID-19 infection due to their close proximity to the face during surgery, use of cautery, and prolonged time spent with patients while taking layers and suturing. Multispectral optoacoustic tomography is a noninvasive imaging tool that can map skin tumors via optical contrast with accuracy comparable to histologic measurements.⁵ 3-Dimensional facial imaging and printing can be used to calculate tumor surface area for customized masks, leaving sufficient skin for excision and reconstruction. Patient face coverings would cover the nose and mouth, only expose relevant areas near the excision site, and include adjustable/removable ear loops for tumors localized to the ears. A schematic of how 3D technologies can be applied for Mohs micrographic surgery is provided in the Figure.

Coronavirus disease 2019 (COVID-19) has spread across all 7 continents, including 185 countries, and infected more than 21.9 million individuals worldwide as of August 18, 2020, according to the Johns Hopkins Coronavirus Resource Center. It has strained our health care system and affected all specialties, including dermatology. Dermatologists have taken important safety measures by canceling/deferring elective and nonemergency procedures and diagnosing/treating patients via telemedicine. Many residents and attending dermatologists have volunteered to care for COVID-19 inpatients and donated personal protective equipment (PPE) to hospitals reporting shortages.¹ As we prepare to treat increasing numbers of in-office patients, there will be a critical need for PPE. We highlight the use of 3-dimensional (3D) imaging and printing technologies as it applies to the dermatology outpatient setting.

N95 masks are necessary during the COVID-19 pandemic because they effectively filter at least 95% of 0.3-μm airborne particles and provide adequate face seals.¹ 3-Dimensional imaging integrated with 3D printers can be used to scan precise facial parameters (eg, jawline, nose) and account for facial hair density and length to produce comfortable tailored N95 masks and face seals.^1,2 3-Dimensional printing utilizes robotics and computer-aided design systems to layer and deposit biomaterials, thereby creating cost-effective, customizable, mechanically stable, and biocompatible constructs.^1,3 An ideal 3D-printed N95 mask would be printed via fused deposition modeling, consisting of a combination of lightweight and fatigue-resistant biomaterials, including electrostatic nonwoven polypropylene and styrene-(ethylene-butylene)-styrene.^1,4 The resulting masks, made from industrial-grade raw materials, are practical alternatives for dermatology practices with insufficient supplies.

Face shields offer an additional layer of safety for the face and mucosae and also may provide longevity for N95 masks. Using synthetic polymers such as polycarbonate and polyethylene, 3D printers can be used to construct face shields via fused deposition modeling.¹ These face shields may be worn over N95 masks and then can be sanitized and reused.

Mohs surgeons and staff may be at particularly high risk for COVID-19 infection due to their close proximity to the face during surgery, use of cautery, and prolonged time spent with patients while taking layers and suturing. Multispectral optoacoustic tomography is a noninvasive imaging tool that can map skin tumors via optical contrast with accuracy comparable to histologic measurements.⁵ 3-Dimensional facial imaging and printing can be used to calculate tumor surface area for customized masks, leaving sufficient skin for excision and reconstruction. Patient face coverings would cover the nose and mouth, only expose relevant areas near the excision site, and include adjustable/removable ear loops for tumors localized to the ears. A schematic of how 3D technologies can be applied for Mohs micrographic surgery is provided in the Figure.

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

A dult Siphonaptera (fleas) are highly adapted to life on the surface of their hosts. Their small 2- to 10-mm bodies are laterally flattened and wingless. They utilize particularly strong hind legs for jumping up to 150 times their body length and backward-directed spines on their legs and bodies for moving forward through fur, hair, and feathers. Xenopsylla cheopis , the oriental rat flea, lacks pronotal and genal combs and has a mesopleuron divided by internal scleritinization (Figure). These features differentiate the species from its close relatives, Ctenocephalides (cat and dog fleas), which have both sets of combs, as well as Pulex irritans (human flea), which do not have a divided mesopleuron. ^1,2

Flea-borne infections are extremely important to public health and are present throughout the world. Further, humidity and warmth are essential for the life cycle of many species of fleas. Predicted global warming likely will increase their distribution, allowing the spread of diseases they carry into previously untouched areas.¹ Therefore, it is important to continue to examine species that carry particularly dangerous pathogens, such as X cheopis.

Disease Vector

Xenopsylla cheopis primarily is known for being a vector in the transmission of Yersinia pestis, the etiologic agent of the plague. Plague occurs in 3 forms: bubonic, pneumonic, and septicemic. It has caused major epidemics throughout history, the most widely known being the Black Death, which lasted for 130 years, beginning in the 1330s in China and spreading into Europe where it wiped out one-third of the population. However, bubonic plague is thought to have caused documented outbreaks as early as 320 bce, and it still remains endemic today.^3,4

Between January 2010 and December 2015, 3248 cases of plague in humans were reported, resulting in 584 deaths worldwide.⁵ It is thought that the plague originated in Central Asia, and this area still is a focus of disease. However, the at-risk population is reduced to breeders and hunters of gerbils and marmots, the main reservoirs in the area. In Africa, 4 countries still regularly report cases, with Madagascar being the most severely affected country in the world.⁵ The Democratic Republic of the Congo, Uganda, and Tanzania also are affected. The Americas also experience the plague. There are sporadic cases of bubonic plague in the northwest corner of Peru, mostly in rural areas. In the western United States, plague circulates among wild rodents, resulting in several reported cases each year, with the most recent confirmed case noted in California in August 2020.^5,6 Further adding to its relevance, Y pestis is one of several organisms most likely to be used as a biologic weapon.^3,4

Due to the historical and continued significance of Y pestis, many studies have been performed over the decades regarding its association with X cheopis. It has been discovered that fleas transmit the bacteria to the host in 2 ways. The most well-defined form of transmission occurs after an incubation period of Y pestis in the flea for 7 to 31 days. During this time, the bacteria form a dense biofilm on a valve in the flea foregut—the proventriculus—interfering with its function, which allows regurgitation of the blood and the bacteria it contains into the bite site and consequently disease transmission. The proventriculus can become completely blocked in some fleas, preventing any blood from reaching the midgut and causing starvation. In these scenarios, the flea will make continuous attempts to feed, increasing transmission.⁷ The hemin storage gene, hms, encoding the second messenger molecule cyclic di-GMP plays a critical role in biofilm formation and proventricular blockage.⁸ The phosphoheptose isomerase gene, GmhA, also has been elucidated as crucial in late transmission due to its role in biofilm formation.⁹ Early-phase transmission, or biofilm-independent transmission, has been documented to occur as early as 3 hours after infection of the flea but can occur for up to 4 days.¹⁰ Historically, the importance of early-phase transmission has been overlooked. Research has shown that it likely is crucial to the epizootic transmission of the plague.¹⁰ As a result, the search has begun for genes that contribute to the maintenance of Y pestis in the flea vector during the first 4 days of colonization. It is thought that a key evolutionary development was the selective loss-of-function mutation in a gene essential for the activity of urease, an enzyme that causes acute oral toxicity and mortality in fleas.^11,12 The Yersinia murine toxin gene, Ymt, also allows for early survival of Y pestis in the flea midgut by producing a phospholipase D that protects the bacteria from toxic by-products produced during digestion of blood.^11,13 In addition, gene products that function in lipid A modification are crucial for the ability of Y pestis to resist the action of cationic antimicrobial peptides it produces, such as cecropin A and polymyxin B.¹³

Murine typhus, an acute febrile illness caused by Rickettsia typhi, is another disease that can be spread by oriental rat fleas. It has a worldwide distribution. In the United States, R typhi–induced rickettsia mainly is concentrated in suburban areas of Texas and California where it is thought to be mainly spread by Ctenocephalides, but it also is found in Hawaii where spread by X cheopis has been documented.^14,15 The most common symptoms of rickettsia include fever, headache, arthralgia, and a characteristic rash that is pruritic and maculopapular, starting on the trunk and spreading peripherally but sparing the palms and soles. This rash occurs about a week after the onset of fever.¹⁴Rickettsia felis also has been isolated in the oriental rat flea. However, only a handful of cases of human disease caused by this bacterium have been reported throughout the world, with clinical similarity to murine typhus likely leading to underestimation of disease prevalence.¹⁵Bartonella and other species of bacteria also have been documented to be spread by X cheopis.¹⁶ Unfortunately, the interactions of X cheopis with these other bacteria are not as well studied as its relationship with Y pestis.

Adverse Reactions

A flea bite itself can cause discomfort. It begins as a punctate hemorrhagic area that develops a surrounding wheal within 30 minutes. Over the course of 1 to 2 days, a delayed reaction occurs and there is a transition to an extremely pruritic, papular lesion. Bites often occur in clusters and can persist for weeks.¹

Prevention and Treatment

Control of host animals via extermination and proper sanitation can secondarily reduce the population of X cheopis. Direct pesticide control of the flea population also has been suggested to reduce flea-borne disease. However, insecticides cause a selective pressure on the flea population, leading to populations that are resistant to them. For example, the flea population in Madagascar developed resistance to DDT (dichlorodiphenyltrichloroethane), dieldrin, deltamethrin, and cyfluthrin after their widespread use.¹⁷ Further, a recent study revealed resistance of X cheopis populations to alphacypermethrin, lambda-cyhalothrin, and etofenprox, none of which were used in mass vector control, indicating that some cross-resistance mechanism between these and the extensively used insecticides may exist. With the development of widespread resistance to most pesticides, flea control in endemic areas is difficult. Insecticide targeting to fleas on rodents (eg, rodent bait containing insecticide) can allow for more targeted insecticide treatment, limiting the development of resistance.¹⁷ Recent development of a maceration protocol used to detect zoonotic pathogens in fleas in the field also will allow management with pesticides to be targeted geographically and temporally where infected vectors are located.¹⁸ Research of the interaction between vector, pathogen, and insect microbiome also should continue, as it may allow for development of biopesticides, limiting the use of chemical pesticides all together. The strategy is based on the introduction of microorganisms that can reduce vector lifespan or their ability to transmit pathogens.¹⁷

When flea-transmitted diseases do occur, treatment with antibiotics is advised. Early treatment of the plague with effective antibiotics such as streptomycin, gentamicin, tetracycline, or chloramphenicol for a minimum of 10 days is critical for survival. Additionally, patients with bubonic plague should be isolated for at least 2 days after administration of antibiotics, while patients with the pneumonic form should be isolated for 4 days into therapy to prevent the spread of disease. Prophylactic therapy for individuals who come into contact with infected individuals also is advised.⁴ Patients with murine typhus typically respond to doxycycline, tetracycline, or fluoroquinolones. The few cases of R felis–induced disease have responded to doxycycline. Of note, short courses of treatment of doxycycline are appropriate and safe in young children. The short (3–7 day) nature of the course limits the chances of teeth staining.¹⁴

Practice Gap

The Centers for Disease Control and Prevention recommends handwashing with soap and water or using alcohol-based hand sanitizers to prevent transmission of coronavirus disease 2019. Five steps are delineated for effective handwashing: wetting, lathering, scrubbing, rinsing, and drying. Although alcohol-based sanitizers may be perceived as more damaging to the skin, they are less likely to cause dermatitis than handwashing with soap and water.¹ Instructions are precise for handwashing, while there are no recommendations for effective use of alcohol-based hand sanitizers. A common inquiry regarding alcohol-based hand sanitizers is the volume needed for efficacy without causing skin irritation.

The Technique

Approximately 1 mL of alcohol-based hand sanitizer is recommended by some manufacturers. However, abundant evidence refutes this recommendation, including a study that tested the microbial efficacy of alcohol-based sanitizers by volume. A volume of 2 mL was necessary to achieve the 2.0 log reduction of contaminants as required by the US Food and Drug Administration for antimicrobial efficacy.² The precise measurement of hand sanitizer using a calibrated syringe before each use is impractical. Thus, we recommend using a screw-top toothpaste cap to assist in approximating the necessary volume (Figure). The cap holds approximately 1 mL of liquid as measured using a syringe; therefore, 2 caps filled with sanitizer should be used.

Practice Implications

The general public may be underutilizing hand sanitizer due to fear of excessive skin irritation or supply shortages, which will reduce efficacy. Patients and physicians can use this simple visual approximation to ensure adequate use of hand sanitizer volume.

Practice Gap

The Centers for Disease Control and Prevention recommends handwashing with soap and water or using alcohol-based hand sanitizers to prevent transmission of coronavirus disease 2019. Five steps are delineated for effective handwashing: wetting, lathering, scrubbing, rinsing, and drying. Although alcohol-based sanitizers may be perceived as more damaging to the skin, they are less likely to cause dermatitis than handwashing with soap and water.¹ Instructions are precise for handwashing, while there are no recommendations for effective use of alcohol-based hand sanitizers. A common inquiry regarding alcohol-based hand sanitizers is the volume needed for efficacy without causing skin irritation.

The Technique

Approximately 1 mL of alcohol-based hand sanitizer is recommended by some manufacturers. However, abundant evidence refutes this recommendation, including a study that tested the microbial efficacy of alcohol-based sanitizers by volume. A volume of 2 mL was necessary to achieve the 2.0 log reduction of contaminants as required by the US Food and Drug Administration for antimicrobial efficacy.² The precise measurement of hand sanitizer using a calibrated syringe before each use is impractical. Thus, we recommend using a screw-top toothpaste cap to assist in approximating the necessary volume (Figure). The cap holds approximately 1 mL of liquid as measured using a syringe; therefore, 2 caps filled with sanitizer should be used.

Practice Implications

The general public may be underutilizing hand sanitizer due to fear of excessive skin irritation or supply shortages, which will reduce efficacy. Patients and physicians can use this simple visual approximation to ensure adequate use of hand sanitizer volume.

Practice Gap

The Centers for Disease Control and Prevention recommends handwashing with soap and water or using alcohol-based hand sanitizers to prevent transmission of coronavirus disease 2019. Five steps are delineated for effective handwashing: wetting, lathering, scrubbing, rinsing, and drying. Although alcohol-based sanitizers may be perceived as more damaging to the skin, they are less likely to cause dermatitis than handwashing with soap and water.¹ Instructions are precise for handwashing, while there are no recommendations for effective use of alcohol-based hand sanitizers. A common inquiry regarding alcohol-based hand sanitizers is the volume needed for efficacy without causing skin irritation.

The Technique

Approximately 1 mL of alcohol-based hand sanitizer is recommended by some manufacturers. However, abundant evidence refutes this recommendation, including a study that tested the microbial efficacy of alcohol-based sanitizers by volume. A volume of 2 mL was necessary to achieve the 2.0 log reduction of contaminants as required by the US Food and Drug Administration for antimicrobial efficacy.² The precise measurement of hand sanitizer using a calibrated syringe before each use is impractical. Thus, we recommend using a screw-top toothpaste cap to assist in approximating the necessary volume (Figure). The cap holds approximately 1 mL of liquid as measured using a syringe; therefore, 2 caps filled with sanitizer should be used.

Practice Implications

The general public may be underutilizing hand sanitizer due to fear of excessive skin irritation or supply shortages, which will reduce efficacy. Patients and physicians can use this simple visual approximation to ensure adequate use of hand sanitizer volume.

Diagnoses of 12 common pediatric infectious diseases in a large pediatric primary care network declined significantly in the weeks after COVID-19 social distancing (SD) was enacted in Massachusetts, compared with the same time period in 2019, an analysis of EHR data has shown.

ArtMarie/E+

While declines in infectious disease transmission with SD are not surprising, “these data demonstrate the extent to which transmission of common pediatric infections can be altered when close contact with other children is eliminated,” Jonathan Hatoun, MD, MPH of the Pediatric Physicians’ Organization at Children’s in Brookline, Mass., and coauthors wrote in Pediatrics . “Notably, three of the studied diseases, namely, influenza, croup, and bronchiolitis, essentially disappeared with [social distancing].”

The researchers analyzed the weekly incidence of each diagnosis for similar calendar periods in 2019 and 2020. A pre-SD period was defined as week 1-9, starting on Jan. 1, and a post-SD period was defined as week 13-18. (The several-week gap represented an implementation period as social distancing was enacted in the state earlier in 2020, from a declared statewide state of emergency through school closures and stay-at-home advisories.)

To isolate the effect of widespread SD, they performed a “difference-in-differences regression analysis, with diagnosis count as a function of calendar year, time period (pre-SD versus post-SD) and the interaction between the two.” The Massachusetts pediatric network provides care for approximately 375,000 children in 100 locations around the state.

In their research brief, Dr. Hatoun and coauthors presented weekly rates expressed as diagnoses per 100,000 patients per day. The rate of bronchiolitis, for instance, was 18 and 8 in the pre- and post-SD–equivalent weeks of 2019, respectively, and 20 and 0.6 in the pre- and post-SD weeks of 2020. Their analysis showed the rate in the 2020 post-SD period to be 10 diagnoses per 100,000 patients per day lower than they would have expected based on the 2019 trend.

Rates of pneumonia, acute otitis media, and streptococcal pharyngitis were similarly 14, 85, and 31 diagnoses per 100,000 patients per day lower, respectively. The prevalence of each of the other conditions analyzed – the common cold, croup, gastroenteritis, nonstreptococcal pharyngitis, sinusitis, skin and soft tissue infections, and urinary tract infection (UTI) – also was significantly lower in the 2020 post-SD period than would be expected based on 2019 data (P < .001 for all diagnoses).
 

Putting things in perspective

“This study puts numbers to the sense that we have all had in pediatrics – that social distancing appears to have had a dramatic impact on the transmission of common childhood infectious diseases, especially other respiratory viral pathogens,” Audrey R. John, MD, PhD, chief of the division of pediatric infectious disease at Children’s Hospital of Philadelphia, said in an interview.

The authors acknowledged the possible role of families not seeking care, but said that a smaller decrease in diagnoses of UTI – generally not a contagious disease – “suggests that changes in care-seeking behavior had a relatively modest effect on the other observed declines.” (The rate of UTI for the pre- and post-SD periods was 3.3 and 3.7 per 100,000 patients per day in 2019, and 3.4 and 2.4 in 2020, for a difference in differences of –1.5).

In an accompanying editorial, David W. Kimberlin, MD and Erica C. Bjornstad, MD, PhD, MPH, of the University of Alabama at Birmingham, called the report “provocative” and wrote that similar observations of infections dropping during periods of isolation – namely, dramatic declines in influenza and other respiratory viruses in Seattle after a record snowstorm in 2019 – combined with findings from other modeling studies “suggest that the decline [reported in Boston] is indeed real” (Pediatrics 2020. doi: 10.1542/peds.2020-019232).

However, “we also now know that immunization rates for American children have plummeted since the onset of the SARS-CoV-2 pandemic [because of a] ... dramatic decrease in the use of health care during the first months of the pandemic,” they wrote. “Viewed through this lens,” the declines reported in Boston may reflect inflections going “undiagnosed and untreated.”

Ultimately, Dr. Kimberlin and Dr. Bjornstad said, “the verdict remains out.”

Dr. John said that she and others are “concerned about children not seeking care in a timely manner, and [concerned] that reductions in reported infections might be due to a lack of recognition rather than a lack of transmission.”

In Philadelphia, however, declines in admissions for asthma exacerbations, “which are often caused by respiratory viral infections, suggests that this may not be the case,” said Dr. John, who was asked to comment on the study.

In addition, she said, the Massachusetts data showing that UTI diagnoses “are nearly as common this year as in 2019” are “reassuring.”
 

Are there lessons for the future?

Coauthor Louis Vernacchio, MD, MSc, chief medical officer of the Pediatric Physicians’ Organization at Children’s network, said in an interview that beyond the pandemic, it’s likely that “more careful attention to proven infection control practices in daycares and schools could reduce the burden of common infectious diseases in children.”

Dr. John similarly sees a long-term value of quantifying the impact of social distancing. “We’ve always known [for instance] that bronchiolitis is the result of viral infection.” Findings like the Massachusetts data “will help us advise families who might be trying to protect their premature infants (at risk for severe bronchiolitis) through social distancing.”

The analysis covered both in-person and telemedicine encounters occurring on weekdays.

The authors of the research brief indicated they have no relevant financial disclosures and there was no external funding. The authors of the commentary also reported they have no relevant financial disclosures, and Dr. John said she had no relevant financial disclosures.

SOURCE: Hatoun J et al. Pediatrics. 2020. doi: 10.1542/peds.2020-006460.

Diagnoses of 12 common pediatric infectious diseases in a large pediatric primary care network declined significantly in the weeks after COVID-19 social distancing (SD) was enacted in Massachusetts, compared with the same time period in 2019, an analysis of EHR data has shown.

ArtMarie/E+

While declines in infectious disease transmission with SD are not surprising, “these data demonstrate the extent to which transmission of common pediatric infections can be altered when close contact with other children is eliminated,” Jonathan Hatoun, MD, MPH of the Pediatric Physicians’ Organization at Children’s in Brookline, Mass., and coauthors wrote in Pediatrics . “Notably, three of the studied diseases, namely, influenza, croup, and bronchiolitis, essentially disappeared with [social distancing].”

The researchers analyzed the weekly incidence of each diagnosis for similar calendar periods in 2019 and 2020. A pre-SD period was defined as week 1-9, starting on Jan. 1, and a post-SD period was defined as week 13-18. (The several-week gap represented an implementation period as social distancing was enacted in the state earlier in 2020, from a declared statewide state of emergency through school closures and stay-at-home advisories.)

To isolate the effect of widespread SD, they performed a “difference-in-differences regression analysis, with diagnosis count as a function of calendar year, time period (pre-SD versus post-SD) and the interaction between the two.” The Massachusetts pediatric network provides care for approximately 375,000 children in 100 locations around the state.

In their research brief, Dr. Hatoun and coauthors presented weekly rates expressed as diagnoses per 100,000 patients per day. The rate of bronchiolitis, for instance, was 18 and 8 in the pre- and post-SD–equivalent weeks of 2019, respectively, and 20 and 0.6 in the pre- and post-SD weeks of 2020. Their analysis showed the rate in the 2020 post-SD period to be 10 diagnoses per 100,000 patients per day lower than they would have expected based on the 2019 trend.

Rates of pneumonia, acute otitis media, and streptococcal pharyngitis were similarly 14, 85, and 31 diagnoses per 100,000 patients per day lower, respectively. The prevalence of each of the other conditions analyzed – the common cold, croup, gastroenteritis, nonstreptococcal pharyngitis, sinusitis, skin and soft tissue infections, and urinary tract infection (UTI) – also was significantly lower in the 2020 post-SD period than would be expected based on 2019 data (P < .001 for all diagnoses).
 

Putting things in perspective

“This study puts numbers to the sense that we have all had in pediatrics – that social distancing appears to have had a dramatic impact on the transmission of common childhood infectious diseases, especially other respiratory viral pathogens,” Audrey R. John, MD, PhD, chief of the division of pediatric infectious disease at Children’s Hospital of Philadelphia, said in an interview.

The authors acknowledged the possible role of families not seeking care, but said that a smaller decrease in diagnoses of UTI – generally not a contagious disease – “suggests that changes in care-seeking behavior had a relatively modest effect on the other observed declines.” (The rate of UTI for the pre- and post-SD periods was 3.3 and 3.7 per 100,000 patients per day in 2019, and 3.4 and 2.4 in 2020, for a difference in differences of –1.5).

In an accompanying editorial, David W. Kimberlin, MD and Erica C. Bjornstad, MD, PhD, MPH, of the University of Alabama at Birmingham, called the report “provocative” and wrote that similar observations of infections dropping during periods of isolation – namely, dramatic declines in influenza and other respiratory viruses in Seattle after a record snowstorm in 2019 – combined with findings from other modeling studies “suggest that the decline [reported in Boston] is indeed real” (Pediatrics 2020. doi: 10.1542/peds.2020-019232).

However, “we also now know that immunization rates for American children have plummeted since the onset of the SARS-CoV-2 pandemic [because of a] ... dramatic decrease in the use of health care during the first months of the pandemic,” they wrote. “Viewed through this lens,” the declines reported in Boston may reflect inflections going “undiagnosed and untreated.”

Ultimately, Dr. Kimberlin and Dr. Bjornstad said, “the verdict remains out.”

Dr. John said that she and others are “concerned about children not seeking care in a timely manner, and [concerned] that reductions in reported infections might be due to a lack of recognition rather than a lack of transmission.”

In Philadelphia, however, declines in admissions for asthma exacerbations, “which are often caused by respiratory viral infections, suggests that this may not be the case,” said Dr. John, who was asked to comment on the study.

In addition, she said, the Massachusetts data showing that UTI diagnoses “are nearly as common this year as in 2019” are “reassuring.”
 

Are there lessons for the future?

Coauthor Louis Vernacchio, MD, MSc, chief medical officer of the Pediatric Physicians’ Organization at Children’s network, said in an interview that beyond the pandemic, it’s likely that “more careful attention to proven infection control practices in daycares and schools could reduce the burden of common infectious diseases in children.”

Dr. John similarly sees a long-term value of quantifying the impact of social distancing. “We’ve always known [for instance] that bronchiolitis is the result of viral infection.” Findings like the Massachusetts data “will help us advise families who might be trying to protect their premature infants (at risk for severe bronchiolitis) through social distancing.”

The analysis covered both in-person and telemedicine encounters occurring on weekdays.

The authors of the research brief indicated they have no relevant financial disclosures and there was no external funding. The authors of the commentary also reported they have no relevant financial disclosures, and Dr. John said she had no relevant financial disclosures.

SOURCE: Hatoun J et al. Pediatrics. 2020. doi: 10.1542/peds.2020-006460.

Diagnoses of 12 common pediatric infectious diseases in a large pediatric primary care network declined significantly in the weeks after COVID-19 social distancing (SD) was enacted in Massachusetts, compared with the same time period in 2019, an analysis of EHR data has shown.

ArtMarie/E+

While declines in infectious disease transmission with SD are not surprising, “these data demonstrate the extent to which transmission of common pediatric infections can be altered when close contact with other children is eliminated,” Jonathan Hatoun, MD, MPH of the Pediatric Physicians’ Organization at Children’s in Brookline, Mass., and coauthors wrote in Pediatrics . “Notably, three of the studied diseases, namely, influenza, croup, and bronchiolitis, essentially disappeared with [social distancing].”

The researchers analyzed the weekly incidence of each diagnosis for similar calendar periods in 2019 and 2020. A pre-SD period was defined as week 1-9, starting on Jan. 1, and a post-SD period was defined as week 13-18. (The several-week gap represented an implementation period as social distancing was enacted in the state earlier in 2020, from a declared statewide state of emergency through school closures and stay-at-home advisories.)

To isolate the effect of widespread SD, they performed a “difference-in-differences regression analysis, with diagnosis count as a function of calendar year, time period (pre-SD versus post-SD) and the interaction between the two.” The Massachusetts pediatric network provides care for approximately 375,000 children in 100 locations around the state.

In their research brief, Dr. Hatoun and coauthors presented weekly rates expressed as diagnoses per 100,000 patients per day. The rate of bronchiolitis, for instance, was 18 and 8 in the pre- and post-SD–equivalent weeks of 2019, respectively, and 20 and 0.6 in the pre- and post-SD weeks of 2020. Their analysis showed the rate in the 2020 post-SD period to be 10 diagnoses per 100,000 patients per day lower than they would have expected based on the 2019 trend.

Rates of pneumonia, acute otitis media, and streptococcal pharyngitis were similarly 14, 85, and 31 diagnoses per 100,000 patients per day lower, respectively. The prevalence of each of the other conditions analyzed – the common cold, croup, gastroenteritis, nonstreptococcal pharyngitis, sinusitis, skin and soft tissue infections, and urinary tract infection (UTI) – also was significantly lower in the 2020 post-SD period than would be expected based on 2019 data (P < .001 for all diagnoses).
 

Putting things in perspective

“This study puts numbers to the sense that we have all had in pediatrics – that social distancing appears to have had a dramatic impact on the transmission of common childhood infectious diseases, especially other respiratory viral pathogens,” Audrey R. John, MD, PhD, chief of the division of pediatric infectious disease at Children’s Hospital of Philadelphia, said in an interview.

The authors acknowledged the possible role of families not seeking care, but said that a smaller decrease in diagnoses of UTI – generally not a contagious disease – “suggests that changes in care-seeking behavior had a relatively modest effect on the other observed declines.” (The rate of UTI for the pre- and post-SD periods was 3.3 and 3.7 per 100,000 patients per day in 2019, and 3.4 and 2.4 in 2020, for a difference in differences of –1.5).

In an accompanying editorial, David W. Kimberlin, MD and Erica C. Bjornstad, MD, PhD, MPH, of the University of Alabama at Birmingham, called the report “provocative” and wrote that similar observations of infections dropping during periods of isolation – namely, dramatic declines in influenza and other respiratory viruses in Seattle after a record snowstorm in 2019 – combined with findings from other modeling studies “suggest that the decline [reported in Boston] is indeed real” (Pediatrics 2020. doi: 10.1542/peds.2020-019232).

However, “we also now know that immunization rates for American children have plummeted since the onset of the SARS-CoV-2 pandemic [because of a] ... dramatic decrease in the use of health care during the first months of the pandemic,” they wrote. “Viewed through this lens,” the declines reported in Boston may reflect inflections going “undiagnosed and untreated.”

Ultimately, Dr. Kimberlin and Dr. Bjornstad said, “the verdict remains out.”

Dr. John said that she and others are “concerned about children not seeking care in a timely manner, and [concerned] that reductions in reported infections might be due to a lack of recognition rather than a lack of transmission.”

In Philadelphia, however, declines in admissions for asthma exacerbations, “which are often caused by respiratory viral infections, suggests that this may not be the case,” said Dr. John, who was asked to comment on the study.

In addition, she said, the Massachusetts data showing that UTI diagnoses “are nearly as common this year as in 2019” are “reassuring.”
 

Are there lessons for the future?

Coauthor Louis Vernacchio, MD, MSc, chief medical officer of the Pediatric Physicians’ Organization at Children’s network, said in an interview that beyond the pandemic, it’s likely that “more careful attention to proven infection control practices in daycares and schools could reduce the burden of common infectious diseases in children.”

Dr. John similarly sees a long-term value of quantifying the impact of social distancing. “We’ve always known [for instance] that bronchiolitis is the result of viral infection.” Findings like the Massachusetts data “will help us advise families who might be trying to protect their premature infants (at risk for severe bronchiolitis) through social distancing.”

The analysis covered both in-person and telemedicine encounters occurring on weekdays.

The authors of the research brief indicated they have no relevant financial disclosures and there was no external funding. The authors of the commentary also reported they have no relevant financial disclosures, and Dr. John said she had no relevant financial disclosures.

SOURCE: Hatoun J et al. Pediatrics. 2020. doi: 10.1542/peds.2020-006460.

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

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

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

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

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

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

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The number of children infected with COVID-19 rose by 7.8% during the week ending Sept. 3, putting the United States over the half-million mark in cumulative child cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.

“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.

Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.

“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.

The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).

“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”

The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.

To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.

“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.

[email protected]

The number of children infected with COVID-19 rose by 7.8% during the week ending Sept. 3, putting the United States over the half-million mark in cumulative child cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.

“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.

Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.

“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.

The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).

“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”

The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.

To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.

“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.

[email protected]

The number of children infected with COVID-19 rose by 7.8% during the week ending Sept. 3, putting the United States over the half-million mark in cumulative child cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.

“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.

Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.

“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.

The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).

“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”

The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.

To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.

“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.

[email protected]

Like most family medicine residencies, our teaching nursing home was struck with a COVID-19 outbreak. Within 10 days, I was the sole physician responsible for 15 patients with varying degrees of illness, quarantined behind the fire doors of a wing of a Memory Support Unit. My daily work there over the course of the next month prompted me to reflect on some of the core principles of family medicine, and health care, that are vital to effective patient care during a pandemic. My experience provided the following reminders:

Work as a team. Gowned, gloved, and masked behind the fire doors, our world shrank to our patients and a 4-person team comprised of a nurse, 2 nursing assistants, and me. For the first time in the 10+ years I’ve worked at that facility, I actually asked for and memorized the names of everyone I was working with that day. Without an intercom or other telecommunications system, it became important for me to be able to call for my team members by name for immediate help. We had to depend on one another to make sure all patients were hydrated and fed, to avert falls whenever possible, to intervene early when dementia-­associated behaviors were escalating, and to recognize when patients were crashing.

I began asking for the names of everyone I was working with that day and I observed, first-hand, the great finesse that nurses display in their efforts to de-escalate disruptive behaviors.

We also had to depend on each other to ensure that our personal protective equipment remained properly placed, to combat the psychological sense of isolation that quarantine environments engender, and to placate a gnawing undercurrent of unease while working around a potentially deadly pathogen.

Develop clinical routines. Having listened to other medical directors whose nursing homes were affected by the pandemic earlier than we were, and hearing about potentially avoidable complications, we developed clinical routines. This began with identifying any patients with diabetes whose poor appetites while acutely ill could send them into hypoglycemia. We devised a daily clinical report sheet that included vital signs, date of positive COVID-19 test, global clinical status, and advance directives. Unlike the usual mode of working almost in parallel, I began my workday with a “sign-out” from the nurse, then started examining each patient.

Under the strain of this unusual environment and novel circumstances, we communicated more and more often. This allowed us to quickly recognize and communicate emerging changes in the clinical status of a patient by sharing our observations of subtle, nonspecific “sub-threshold” indicators.

Clarify the goals of care. Since most of the patients in the COVID-19 unit were under the long-term care of other attending physicians, it was important for me to understand the wishes of the patient or surrogate decision maker, should life-threatening complications occur. While all affected patients were long-term residents of a memory support unit, some had full-code advance directives. I quickly realized that what was first necessary was to develop rapport and trust with the families who didn’t know me, then discuss goals of care, and finally assure that the advance directives were in congruence with their stated goals. What helped families gain trust in me was knowing that I was seeing their loved one daily, that I was committed to helping the patient survive this infection, and that I was willing to come back to the facility if a crisis occurred—even at night, if necessary.

Appreciate the daily work of team members. One of my greatest worries was dehydration. When elders were acutely ill and eating and drinking poorly, I would assist with feeding and offering liquids. I quickly came to appreciate how complex and subtle this seemingly mundane task can be. Learning the proper pace and portion size, even choosing the right conversation topic and tone, could make the difference between a patient “shutting down” and refusing all nourishment and successfully drinking a 360-cc cup of a high-nutrient shake.

Continue to: In the disrupted routines...

In the disrupted routines and altered physical environments of the COVID-19 unit, the psychological and behavioral complications of dementia intensified for some patients. I observed first-hand the great patience, kindness, and finesse that nurses and nursing assistants display in their efforts to de-escalate and prevent disruptive behaviors.

Empathize with (and appreciate) families. Families tearfully reminded me that they had been suffering from the absence of contact with their loved ones for months; COVID-19 added to that trauma for many of them. They talked about the missed graduations, birthdays, and other precious times together that were lost because of the quarantine.

Families also prevented me from making mistakes. When I ordered nitrofurantoin for a patient with a urinary tract infection, her son called me and respectfully requested I “just check and make sure” it would not cause a problem, given her G6PD deficiency. He prevented me from prescribing an antibiotic contraindicated in that condition.

Bring forward the lessons learned. The COVID-19 outbreak has passed through our nursing home—at least for now. I perceive a subtle shift in how we continue to interact with one another. Behind the masks, we make a little more eye contact; we more often address each other by name; and we acknowledge a greater mutual respect.

The shared experience of COVID-19 has brought us all a little closer together, and in the end, our patients have benefitted.

Like most family medicine residencies, our teaching nursing home was struck with a COVID-19 outbreak. Within 10 days, I was the sole physician responsible for 15 patients with varying degrees of illness, quarantined behind the fire doors of a wing of a Memory Support Unit. My daily work there over the course of the next month prompted me to reflect on some of the core principles of family medicine, and health care, that are vital to effective patient care during a pandemic. My experience provided the following reminders:

Work as a team. Gowned, gloved, and masked behind the fire doors, our world shrank to our patients and a 4-person team comprised of a nurse, 2 nursing assistants, and me. For the first time in the 10+ years I’ve worked at that facility, I actually asked for and memorized the names of everyone I was working with that day. Without an intercom or other telecommunications system, it became important for me to be able to call for my team members by name for immediate help. We had to depend on one another to make sure all patients were hydrated and fed, to avert falls whenever possible, to intervene early when dementia-­associated behaviors were escalating, and to recognize when patients were crashing.

I began asking for the names of everyone I was working with that day and I observed, first-hand, the great finesse that nurses display in their efforts to de-escalate disruptive behaviors.

We also had to depend on each other to ensure that our personal protective equipment remained properly placed, to combat the psychological sense of isolation that quarantine environments engender, and to placate a gnawing undercurrent of unease while working around a potentially deadly pathogen.

Develop clinical routines. Having listened to other medical directors whose nursing homes were affected by the pandemic earlier than we were, and hearing about potentially avoidable complications, we developed clinical routines. This began with identifying any patients with diabetes whose poor appetites while acutely ill could send them into hypoglycemia. We devised a daily clinical report sheet that included vital signs, date of positive COVID-19 test, global clinical status, and advance directives. Unlike the usual mode of working almost in parallel, I began my workday with a “sign-out” from the nurse, then started examining each patient.

Under the strain of this unusual environment and novel circumstances, we communicated more and more often. This allowed us to quickly recognize and communicate emerging changes in the clinical status of a patient by sharing our observations of subtle, nonspecific “sub-threshold” indicators.

Clarify the goals of care. Since most of the patients in the COVID-19 unit were under the long-term care of other attending physicians, it was important for me to understand the wishes of the patient or surrogate decision maker, should life-threatening complications occur. While all affected patients were long-term residents of a memory support unit, some had full-code advance directives. I quickly realized that what was first necessary was to develop rapport and trust with the families who didn’t know me, then discuss goals of care, and finally assure that the advance directives were in congruence with their stated goals. What helped families gain trust in me was knowing that I was seeing their loved one daily, that I was committed to helping the patient survive this infection, and that I was willing to come back to the facility if a crisis occurred—even at night, if necessary.

Appreciate the daily work of team members. One of my greatest worries was dehydration. When elders were acutely ill and eating and drinking poorly, I would assist with feeding and offering liquids. I quickly came to appreciate how complex and subtle this seemingly mundane task can be. Learning the proper pace and portion size, even choosing the right conversation topic and tone, could make the difference between a patient “shutting down” and refusing all nourishment and successfully drinking a 360-cc cup of a high-nutrient shake.

Continue to: In the disrupted routines...

In the disrupted routines and altered physical environments of the COVID-19 unit, the psychological and behavioral complications of dementia intensified for some patients. I observed first-hand the great patience, kindness, and finesse that nurses and nursing assistants display in their efforts to de-escalate and prevent disruptive behaviors.

Empathize with (and appreciate) families. Families tearfully reminded me that they had been suffering from the absence of contact with their loved ones for months; COVID-19 added to that trauma for many of them. They talked about the missed graduations, birthdays, and other precious times together that were lost because of the quarantine.

Families also prevented me from making mistakes. When I ordered nitrofurantoin for a patient with a urinary tract infection, her son called me and respectfully requested I “just check and make sure” it would not cause a problem, given her G6PD deficiency. He prevented me from prescribing an antibiotic contraindicated in that condition.

Bring forward the lessons learned. The COVID-19 outbreak has passed through our nursing home—at least for now. I perceive a subtle shift in how we continue to interact with one another. Behind the masks, we make a little more eye contact; we more often address each other by name; and we acknowledge a greater mutual respect.

The shared experience of COVID-19 has brought us all a little closer together, and in the end, our patients have benefitted.

Like most family medicine residencies, our teaching nursing home was struck with a COVID-19 outbreak. Within 10 days, I was the sole physician responsible for 15 patients with varying degrees of illness, quarantined behind the fire doors of a wing of a Memory Support Unit. My daily work there over the course of the next month prompted me to reflect on some of the core principles of family medicine, and health care, that are vital to effective patient care during a pandemic. My experience provided the following reminders:

Work as a team. Gowned, gloved, and masked behind the fire doors, our world shrank to our patients and a 4-person team comprised of a nurse, 2 nursing assistants, and me. For the first time in the 10+ years I’ve worked at that facility, I actually asked for and memorized the names of everyone I was working with that day. Without an intercom or other telecommunications system, it became important for me to be able to call for my team members by name for immediate help. We had to depend on one another to make sure all patients were hydrated and fed, to avert falls whenever possible, to intervene early when dementia-­associated behaviors were escalating, and to recognize when patients were crashing.

I began asking for the names of everyone I was working with that day and I observed, first-hand, the great finesse that nurses display in their efforts to de-escalate disruptive behaviors.

We also had to depend on each other to ensure that our personal protective equipment remained properly placed, to combat the psychological sense of isolation that quarantine environments engender, and to placate a gnawing undercurrent of unease while working around a potentially deadly pathogen.

Develop clinical routines. Having listened to other medical directors whose nursing homes were affected by the pandemic earlier than we were, and hearing about potentially avoidable complications, we developed clinical routines. This began with identifying any patients with diabetes whose poor appetites while acutely ill could send them into hypoglycemia. We devised a daily clinical report sheet that included vital signs, date of positive COVID-19 test, global clinical status, and advance directives. Unlike the usual mode of working almost in parallel, I began my workday with a “sign-out” from the nurse, then started examining each patient.

Under the strain of this unusual environment and novel circumstances, we communicated more and more often. This allowed us to quickly recognize and communicate emerging changes in the clinical status of a patient by sharing our observations of subtle, nonspecific “sub-threshold” indicators.

Clarify the goals of care. Since most of the patients in the COVID-19 unit were under the long-term care of other attending physicians, it was important for me to understand the wishes of the patient or surrogate decision maker, should life-threatening complications occur. While all affected patients were long-term residents of a memory support unit, some had full-code advance directives. I quickly realized that what was first necessary was to develop rapport and trust with the families who didn’t know me, then discuss goals of care, and finally assure that the advance directives were in congruence with their stated goals. What helped families gain trust in me was knowing that I was seeing their loved one daily, that I was committed to helping the patient survive this infection, and that I was willing to come back to the facility if a crisis occurred—even at night, if necessary.

Appreciate the daily work of team members. One of my greatest worries was dehydration. When elders were acutely ill and eating and drinking poorly, I would assist with feeding and offering liquids. I quickly came to appreciate how complex and subtle this seemingly mundane task can be. Learning the proper pace and portion size, even choosing the right conversation topic and tone, could make the difference between a patient “shutting down” and refusing all nourishment and successfully drinking a 360-cc cup of a high-nutrient shake.

Continue to: In the disrupted routines...

In the disrupted routines and altered physical environments of the COVID-19 unit, the psychological and behavioral complications of dementia intensified for some patients. I observed first-hand the great patience, kindness, and finesse that nurses and nursing assistants display in their efforts to de-escalate and prevent disruptive behaviors.

Empathize with (and appreciate) families. Families tearfully reminded me that they had been suffering from the absence of contact with their loved ones for months; COVID-19 added to that trauma for many of them. They talked about the missed graduations, birthdays, and other precious times together that were lost because of the quarantine.

Families also prevented me from making mistakes. When I ordered nitrofurantoin for a patient with a urinary tract infection, her son called me and respectfully requested I “just check and make sure” it would not cause a problem, given her G6PD deficiency. He prevented me from prescribing an antibiotic contraindicated in that condition.

Bring forward the lessons learned. The COVID-19 outbreak has passed through our nursing home—at least for now. I perceive a subtle shift in how we continue to interact with one another. Behind the masks, we make a little more eye contact; we more often address each other by name; and we acknowledge a greater mutual respect.

The shared experience of COVID-19 has brought us all a little closer together, and in the end, our patients have benefitted.

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]