Commentary

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Each day, we’re inundated with news about the COVID-19 pandemic and how it continues to strain our health care system and resources. With more than 1.15 million positive cases in the United States and over 67,000 deaths as of this writing, it has been a scary yet humbling experience for everyone. There is no doubt this pandemic will be a defining moment in health care for several reasons. From supply chain disruptions and personal protective equipment (PPE) and ventilator shortages to exhausted caregivers – both physically and mentally – this event has pushed the envelope on finding answers from federal and state authorities. Hospital administrations are working harder than ever to rise to the challenge and do what is best for their frontline staff and, more importantly, the patients and the communities they serve.

The provider experience during COVID-19

Hospitalists are in a unique situation as frontline providers. Managing daily throughput of patients has always been a key role for the specialty. They also play an integral role in their own care teams alongside nurses, trainees, case managers, pharmacists, and others in cohorted COVID-19 units. Now more than ever, such a geographic placement of patients is quickly emerging as a must-have staffing model to reduce risk of cross-contamination and preserving critical PPE supplies. This heightened awareness, coupled with anxiety, sometimes leads to added stress and burnout risk for hospitalists.

Communication is critical in creating situational awareness and reducing anxiety within the teams. This is exactly where hospitalists can lead:

• Active presence in hospital incident command centers and infection control boards
• Close coordination with emergency medicine colleagues and bed placement navigators
• Developing protocols for appropriate testing
• Frequent daily huddles to discuss current state- and hospital-level testing guidelines
• Close involvement in the hospital operations committee
• Advocating for or securing more testing or supplies, especially PPE
• Effective communication about changes in PPE requirements and conservation strategies as per the Centers for Disease Control and Prevention, State Department of Health, and the hospital infection control board
• Crisis-driven changes, including development and review of triage and treatment protocols and elective procedure cancellations
• Census numbers and capacity/staffing adjustments within the team to meet temporary dips and surges in on-service patient volumes
• Frontline caregiver mental and physical health assessment

Daily huddles at key times (e.g., at shift start and end times) can help to identify these barriers. If operational issues arise, there should be a clear channel to escalate them to senior leadership.

Hospitalists could also use several strategies proven to improve staff morale and resilience. For instance, take this time to connect with friends and family virtually, unplug when off from work, explore one’s spiritual self through meditation and prayers, spend time with nature, exercise daily, seek humor, and develop or work on one’s hobby.
 

The patient experience during COVID-19

Some intriguing data is also being released about patient experience during the pandemic. A Press Ganey analysis of 350,000 comments between January and March 2020 shows that patients are looking for more information about their condition, primarily COVID-19 test delays and result notification time. There is also hypervigilance in patients’ minds about hand hygiene and overall cleanliness of the hospital. Patients also seek clarification and transparent explanation of their caregiver’s bedside mannerisms – for example, why did they gown up before entering – and their daily care plans.

Patients have been appreciative of providers and recognize the personal risk frontline staff put themselves through. Communication transparency seems to mitigate concerns about delays of care especially caused by operational challenges as a result of the pandemic.

In surveys specifically related to experiences including COVID-19, patients were more likely to rate more areas of service lower than in surveys that did not mention COVID-19. The patients also seemed to put more value on the quality of instructions and information they received and on perception of providers’ respect and listening abilities. These insights could prove invaluable in improving care delivery by hospitalists.

Isolation of patients has been shown in multiple studies to have negative outcomes. These patients are up to twice as likely to have an adverse event, and seven times more likely to have treatment-related avoidable adversity, poorer perceived patient experience, and overall perception of being cared for “less.” Add to this a higher level of depression and mental strain, and these patients quickly become “unsatisfied.”

At the ED level, the willingness to let family be present for care was the key area of concern listed – a metric that has changed rapidly since the early days of the pandemic.

The bottom line is these are trying times for everyone – both for providers and patients. Both look up to health system and group leadership for reassurance. Patients and families recognize the risks frontline providers are assuming. However, transparent communication across all levels is the key. Silos are disappearing and team based care is taking center stage.

Beyond the current public health crisis, these efforts will go a long way to create unshakable trust between health systems, providers, patients, and their loved ones.

Dr. Singh is currently the chief of inpatient operations at Adena Health System in Chillicothe, Ohio, where he also has key roles in medical informatics and health IT. He is also the president-elect of the Central Ohio Chapter of SHM.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at dermnews@mdedge.com

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at dermnews@mdedge.com

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.

Inexpensively obtained as a silk industry by-product, sericin is a glycoprotein found to confer various biologic effects.¹ The globular protein sericin has also long been known to exhibit antityrosinase and immunomodulatory activities.^2,3 This column focuses on the wide range of emerging and potential applications of sericin in cutaneous treatments.

Protection against solar radiation and photoaging

Sailesh Patnaik/CCA-SA 4.0 International

Studies in mice to evaluate the potential antioxidant and skin-protective effects of sericin by Zhaorigetu et al. in 2003 revealed that, by diminishing oxidative stress, cyclooxygenase-2 protein, and cell proliferation, sericin exerted a photoprotective effect against acute harm and tumor promotion elicited by UVB.⁴

Using mouse skin models, Dash et al. showed in 2008 that the silk protein sericin derived from the tropical tasar silkworm is a robust antioxidant and photoprotective agent, displaying a capacity to block UVB-induced apoptosis in irradiated (30 mJ/cm² UVB) human keratinocytes and, as compared with the mulberry silkworm, yielding protection against oxidative stress.^5,6

In 2015, Berardesca et al. conducted a randomized, double-blind, vehicle-controlled, split-face study over 8 weeks in 40 women (ages 40-70 years) to assess the antiaging effects of topically applied combination therapy including gold silk sericin, niacinamide, and signaline. The investigators observed significant improvements in stratum corneum hydration, barrier function, skin elasticity, and roughness as compared with skin treated with the control formulation. They concluded that this combination formulation featuring gold silk sericin warrants attention in the arsenal for ameliorating signs of aging female facial skin.⁷

A year earlier, Aramwit and Bang introduced a bacterial nanocellulose gel shown to effectively release silk sericin for facial treatment. Formulated at a pH of 4.5, the bioactive mask exhibited an ultrafine and pure fiber network structure. The authors noted that the gel was less adhesive than the commercially available paper mask, while the silk sericin product displayed greater moisture absorption capacity. In vitro cytotoxicity assessments also revealed that the product is safe for facial treatments.⁸

Cosmeceutical antioxidant for hyperpigmentation

In 2019, Kumar et al. demonstrated the inhibitory effect of topically applied silk sericin derived from Antheraea assamensis against UV-induced melanogenesis in mouse melanoma. They suggested that the formulation shows promise as a cosmeceutical antioxidant agent designed to address hyperpigmentation.³

The previous year, Aramwit et al. demonstrated using an in vitro model that urea-extracted sericin displays a capacity to inhibit melanogenesis by hindering tyrosinase activity, attenuating inflammation and allergic reactions, and reducing the expression of microphthalmia-associated transcription factor, a marker of melanogenesis regulation, in melanocytes and keratinocytes.²

Potential use as an adjunct psoriasis treatment

A combination of naringin (from Citrus maxima) and sericin (from Bombyx mori) was evaluated in 2019 by Deenonpoe et al. for the treatment of psoriasis. They isolated human peripheral blood mononuclear cells from 10 healthy subjects and 10 patients with psoriasis. The combination formulation was much more effective than either compound alone in significantly reducing mRNA expression and the synthesis of proinflammatory cytokines in samples from psoriasis patients. The investigators concluded that the down-regulation of proinflammatory cytokines imparted by the naringin/sericin product points toward its possible clinical use as a complementary treatment for psoriasis and other inflammation-mediated conditions.⁹

Uremic pruritus and burn wounds

A randomized, double-blind, placebo-controlled 6-week study in 2012 conducted by Aramwit et al. assessed the use of sericin cream versus a cream base placebo in the treatment of uremic pruritus in 50 hemodialysis patients, 47 of whom completed the study. Significant differences in the creams were identified, with hydration vastly improved in patients using the sericin cream. Significant reductions in pruritus and dyspigmentation were also observed in the treatment group, with an overall quality of life improvement noted in relation to pain score.¹⁰

Gail Hampshire/Wikimedia Commons CC BY 2.0

The ensuing year, Aramwit et al. showed that silk sericin promoted wound healing in vitro and, when added to silver sulfadiazine cream and evaluated in a randomized, double-blind, standard-controlled study, demonstrated clinical efficacy in healing burn wounds.¹¹

Wound healing

An expanding body of research suggests the role of sericin in wound healing. In 2007, Aramwit et al. found that sericin, which boasts notable hydrophilic qualities, was effective as a wound-healing agent in rats. The tested sericin cream successfully reduced wound size and wound healing time was substantially shorter than in animals treated with control formula. Treatment for 15 days yielded complete healing, no ulceration, and higher collagen levels, as determined by histologic examination, in comparison with control.¹² Other studies using sericin hydrogel as well as a sericin-based nanofibrous matrix with chitosan have demonstrated success in wound healing in mice.^13,14

Human studies

In 2018, Napavichayanun et al. reported on the clinical efficacy and safety of bacterial cellulose wound dressings including silk sericin and PHMB as compared with Bactigras (an antiseptic dressing) as a control in split-thickness skin graft donor-site wound treatment. In this single-blinded, randomized, controlled study of 21 patients, pain scores were significantly lower and wound quality higher in the skin treated with the sericin product. The test formulation was protected against infection without inducing adverse effects.¹⁵

Previously, a silk sericin–releasing wound dressing introduced in 2014 was found to significantly diminish pain and promote more rapid healing in patients with split-thickness skin graft donor sites as compared with treatment with the Bactigras wound dressing.¹⁶

Sericin in tissue repair and as a drug delivery carrier

Sericin is associated with antioxidant and moisturizing properties as well as a mitogenic influence on mammalian cells, with a particular impact on keratinocytes and fibroblasts that render it useful in biomaterials designed for skin tissue repair.¹⁷

Wang et al. have cross-linked dialdehyde carboxymethyl cellulose with silk sericin derived from the B. mori cocoon to develop a film with impressive blood compatibility and cytocompatibility that shows potential for use as a wound dressing, artificial skin, and in tissue engineering.¹⁸

Similarly, Liang et al. have been successful in preparing a medical tissue glue incorporating a gelatin, sericin, and carboxymethyl chitosan blend solution, cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The tissue glue has been found to offer notable biocompatibility and structural traits at low cost.¹⁹

Sericin protein also evinces potential as a biocompatible, bioviable carrier for drug delivery. Suktham et al. showed that resveratrol-loaded sericin nanoparticles robustly hindered growth of colorectal adenocarcinoma cells while cytotoxic to skin fibroblasts, suggesting the viability or potential of sericin nanoparticles as bionanocarriers in a drug delivery system.²⁰ In addition, Tao et al. found silk sericin to be effective when blended with poly(vinyl alcohol) in a hydrogel with antibacterial properties as a drug delivery carrier with potential for use as wound dressing.²¹

Conclusion

There is a plethora of new evidence to justify the inclusion of sericin in dermatologic research and skin care, specifically wound care. Much more research is necessary, though, to explore how the antioxidant and moisturizing activities of the protein may be harnessed to confer skin-protective effects, especially against UV damage.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers,“The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at dermnews@mdedge.com

References

1. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

2. Aramwit P et al. Biol Res. 2018 Nov 29;51(1):54.

3. Kumar JP, Mandal BB. Photochem Photobiol Sci. 2019 Oct 9:18(10):2497-508.

4. Zhaorigetu S et al. J Photochem Photobiol B. 2003 Oct 15;71(1-3):11-7.

5. Dash R et al. Mol Cell Biochem. 2008 Apr;311(1-2):111-9.

6. Dash R et al. BMB Rep. 2008 Mar 31;41(3):236-41.

7. Berardesca E et al. Int J Cosmet Sci. 2015 Dec;37(6):606-12.

8. Aramwit P, Bang N. BMC Biotechnol. 2014 Dec 9;14:104.

9. Deenonpoe R et al. BMC Complement Altern Med. 2019 Jul 10;19(1):168.

10. Aramwit P et al. BMC Nephrol. 2012 Sep 24;13:119.

11. Aramwit P et al. Arch Dermatol Res. 2013 Sep;305(7):585-94.

12. Aramwit P, Sangcakul A. Biosci Biotechnol Biochem. 2007 Oct;71(10):2473-7.

13. Qi C et al. Biomater Sci. 2018 Nov 1;6(11):2859-70.

14. Sapru S et al. Acta Biomater. 2018 Sep 15;78:137-50.

15. Napavichayanun S et al. Arch Dermatol Res. 2018 Dec;310(10):795-805.

16. Siritientong T et al. Pharm Res. 2014 Jan;31(1):104-16.

17. Lamboni L et al. Biotechnol Adv. 2015 Dec;33(8):1855-67.

18. Wang P et al. Carbohydr Polym. 2019 May 15;212:403-11.

19. Liang M et al. J Appl Biomater Funct Mater. 2018 Apr;16(2):97-106.

20. Suktham K et al. Int J Pharm. 2018 Feb 15;537(1-2):48-56.

21. Tao G et al. Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:341-51.

Pityriasis rubra pilaris (PRP) is the name given to a heterogeneous group of rare inflammatory papulosquamous dermatoses. There are six sub-types that can present with various skin findings, however, the cardinal features across sub-types include well-defined, red-orange hued plaques with varying scale, palmoplantar keratoderma, and follicular keratosis. In the more generalized subtypes, there is a characteristic feature of intervening areas of unaffected skin often referred to as “islands of sparing.” The plaques may cover the entire body or just parts of the body such as the elbows and knees, palms and soles. Lesions are generally asymptomatic; occasionally patients complain of mild pruritus. 

Photos courtesy of Robert Silverman, MD

The etiology and pathophysiology of this group of disorders is not well understood. However, there are several hypotheses including dysfunction in vitamin A metabolism, autoimmune dysregulation, as well as environmental and immunologic triggers such as infection and ultraviolet exposure. Although most cases are sporadic, genetics do seem to play a role in the development of some cases. Caspase recruitment domain-containing protein 14 (CARD14) mutations are seen in familial PRP, and occasionally in patients with sporadic PRP, with gain of function mutations. Interestingly, CARD14 mutations are also associated with psoriasis in some individuals.¹ The type-VI PRP variant has been associated with HIV, although this is incredibly rare in pediatrics.²

PRP shows significant clinical diversity, with six subtypes defined by age of onset, distribution, and appearance of lesions, and presence of HIV. This includes type I (classical adult onset), type II (atypical adult onset), type III (classical juvenile onset), type IV (circumscribed juvenile onset), type V (atypical juvenile onset), and type VI (HIV-associated). As mentioned earlier, shared features that appear across subtypes in variable degrees include red-orange papules and plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis.

Of the six subtypes, type III, IV, and V occur in the pediatric population. Type III, classic juvenile PRP, typically occurs within the first 2 years of life or in adolescence. Only 10% of cases fall into this category. It shares similar features to type I PRP including red-orange plaques; islands of sparing, perifollicular hyperkeratotic papules; waxy palmoplantar keratoderma; and the distribution of affected skin is more diffuse overall. While some children clear within a few years, more recent studies stress a more prolonged course similar to the type IV variant.²

Type-IV PRP, also known as circumscribed juvenile PRP, is a focal variant, usually seen in prepubertal children and making up 25% of total cases. Clinically, these patients tend to have sharply demarcated grouped erythematous, follicular papules on the elbows, knees and over bony prominences.²

Type-V PRP is an atypical generalized juvenile variant which affects 5% of patients. It is a non-remitting hereditary condition with classic characteristics similar to type III with additional scleroderma-like changes involving the palms and soles.²

Diagnosis of PRP is based on clinical recognition and biopsy can be important to secure a diagnosis.

PRP, in many cases is self-limited and asymptomatic, and therefore does not necessarily require treatment. In other patients treatment can be challenging, and referral to a pediatric dermatology specialist is reasonable. Most practitioners recommend combination therapy with topical agents (emollients, topical corticosteroids, tazarotene, topical calcineurin inhibitors, and keratolytic agents such as urea, salicylic acid, or alpha-hydroxy acids) for symptomatic management and systemic therapies (methotrexate, isotretinoin) aimed at reducing inflammation. There is some data that CARD14-associated PRP can respond well to targeted biologic therapies.¹

The subtypes of PRP can present in a myriad of ways and often the disease is misdiagnosed. Depending on the particular subtype and findings present, the differential can vary considerably. Commonly, physicians need to consider: psoriasis, seborrheic dermatitis, atopic dermatitis, ichthyoses, and other conditions which can cause erythroderma.³ The characteristic red-orange color and variable associated edema helps to distinguish keratoderma of PRP from psoriasis, atopic dermatitis, ichthyosis, and hereditary palmoplantar keratoderma. Scalp involvement of PRP should be differentiated from the waxy scale of seborrheic dermatitis and the well demarcated silvery scale of psoriasis. History alone may assist in distinguishing PRP from other major causes of generalized erythroderma, although biopsy is warranted in these cases.
 

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital-San Diego and the University of California, San Diego. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. J Am Acad Dermatol. 2018 Sep;79(3):487-94.

2. “Pityriasis Rubra Pilaris” (Treasure Island, Fla.: StatPearls Publishing, July 20, 2019). 3. JAMA Dermatol. 2016 Jun 1;152(6):670-5.

Pityriasis rubra pilaris (PRP) is the name given to a heterogeneous group of rare inflammatory papulosquamous dermatoses. There are six sub-types that can present with various skin findings, however, the cardinal features across sub-types include well-defined, red-orange hued plaques with varying scale, palmoplantar keratoderma, and follicular keratosis. In the more generalized subtypes, there is a characteristic feature of intervening areas of unaffected skin often referred to as “islands of sparing.” The plaques may cover the entire body or just parts of the body such as the elbows and knees, palms and soles. Lesions are generally asymptomatic; occasionally patients complain of mild pruritus. 

Photos courtesy of Robert Silverman, MD

The etiology and pathophysiology of this group of disorders is not well understood. However, there are several hypotheses including dysfunction in vitamin A metabolism, autoimmune dysregulation, as well as environmental and immunologic triggers such as infection and ultraviolet exposure. Although most cases are sporadic, genetics do seem to play a role in the development of some cases. Caspase recruitment domain-containing protein 14 (CARD14) mutations are seen in familial PRP, and occasionally in patients with sporadic PRP, with gain of function mutations. Interestingly, CARD14 mutations are also associated with psoriasis in some individuals.¹ The type-VI PRP variant has been associated with HIV, although this is incredibly rare in pediatrics.²

PRP shows significant clinical diversity, with six subtypes defined by age of onset, distribution, and appearance of lesions, and presence of HIV. This includes type I (classical adult onset), type II (atypical adult onset), type III (classical juvenile onset), type IV (circumscribed juvenile onset), type V (atypical juvenile onset), and type VI (HIV-associated). As mentioned earlier, shared features that appear across subtypes in variable degrees include red-orange papules and plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis.

Of the six subtypes, type III, IV, and V occur in the pediatric population. Type III, classic juvenile PRP, typically occurs within the first 2 years of life or in adolescence. Only 10% of cases fall into this category. It shares similar features to type I PRP including red-orange plaques; islands of sparing, perifollicular hyperkeratotic papules; waxy palmoplantar keratoderma; and the distribution of affected skin is more diffuse overall. While some children clear within a few years, more recent studies stress a more prolonged course similar to the type IV variant.²

Type-IV PRP, also known as circumscribed juvenile PRP, is a focal variant, usually seen in prepubertal children and making up 25% of total cases. Clinically, these patients tend to have sharply demarcated grouped erythematous, follicular papules on the elbows, knees and over bony prominences.²

Type-V PRP is an atypical generalized juvenile variant which affects 5% of patients. It is a non-remitting hereditary condition with classic characteristics similar to type III with additional scleroderma-like changes involving the palms and soles.²

Diagnosis of PRP is based on clinical recognition and biopsy can be important to secure a diagnosis.

PRP, in many cases is self-limited and asymptomatic, and therefore does not necessarily require treatment. In other patients treatment can be challenging, and referral to a pediatric dermatology specialist is reasonable. Most practitioners recommend combination therapy with topical agents (emollients, topical corticosteroids, tazarotene, topical calcineurin inhibitors, and keratolytic agents such as urea, salicylic acid, or alpha-hydroxy acids) for symptomatic management and systemic therapies (methotrexate, isotretinoin) aimed at reducing inflammation. There is some data that CARD14-associated PRP can respond well to targeted biologic therapies.¹

The subtypes of PRP can present in a myriad of ways and often the disease is misdiagnosed. Depending on the particular subtype and findings present, the differential can vary considerably. Commonly, physicians need to consider: psoriasis, seborrheic dermatitis, atopic dermatitis, ichthyoses, and other conditions which can cause erythroderma.³ The characteristic red-orange color and variable associated edema helps to distinguish keratoderma of PRP from psoriasis, atopic dermatitis, ichthyosis, and hereditary palmoplantar keratoderma. Scalp involvement of PRP should be differentiated from the waxy scale of seborrheic dermatitis and the well demarcated silvery scale of psoriasis. History alone may assist in distinguishing PRP from other major causes of generalized erythroderma, although biopsy is warranted in these cases.
 

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital-San Diego and the University of California, San Diego. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. J Am Acad Dermatol. 2018 Sep;79(3):487-94.

2. “Pityriasis Rubra Pilaris” (Treasure Island, Fla.: StatPearls Publishing, July 20, 2019). 3. JAMA Dermatol. 2016 Jun 1;152(6):670-5.

Pityriasis rubra pilaris (PRP) is the name given to a heterogeneous group of rare inflammatory papulosquamous dermatoses. There are six sub-types that can present with various skin findings, however, the cardinal features across sub-types include well-defined, red-orange hued plaques with varying scale, palmoplantar keratoderma, and follicular keratosis. In the more generalized subtypes, there is a characteristic feature of intervening areas of unaffected skin often referred to as “islands of sparing.” The plaques may cover the entire body or just parts of the body such as the elbows and knees, palms and soles. Lesions are generally asymptomatic; occasionally patients complain of mild pruritus. 

Photos courtesy of Robert Silverman, MD

The etiology and pathophysiology of this group of disorders is not well understood. However, there are several hypotheses including dysfunction in vitamin A metabolism, autoimmune dysregulation, as well as environmental and immunologic triggers such as infection and ultraviolet exposure. Although most cases are sporadic, genetics do seem to play a role in the development of some cases. Caspase recruitment domain-containing protein 14 (CARD14) mutations are seen in familial PRP, and occasionally in patients with sporadic PRP, with gain of function mutations. Interestingly, CARD14 mutations are also associated with psoriasis in some individuals.¹ The type-VI PRP variant has been associated with HIV, although this is incredibly rare in pediatrics.²

PRP shows significant clinical diversity, with six subtypes defined by age of onset, distribution, and appearance of lesions, and presence of HIV. This includes type I (classical adult onset), type II (atypical adult onset), type III (classical juvenile onset), type IV (circumscribed juvenile onset), type V (atypical juvenile onset), and type VI (HIV-associated). As mentioned earlier, shared features that appear across subtypes in variable degrees include red-orange papules and plaques, hyperkeratotic follicular papules, and palmoplantar hyperkeratosis.

Of the six subtypes, type III, IV, and V occur in the pediatric population. Type III, classic juvenile PRP, typically occurs within the first 2 years of life or in adolescence. Only 10% of cases fall into this category. It shares similar features to type I PRP including red-orange plaques; islands of sparing, perifollicular hyperkeratotic papules; waxy palmoplantar keratoderma; and the distribution of affected skin is more diffuse overall. While some children clear within a few years, more recent studies stress a more prolonged course similar to the type IV variant.²

Type-IV PRP, also known as circumscribed juvenile PRP, is a focal variant, usually seen in prepubertal children and making up 25% of total cases. Clinically, these patients tend to have sharply demarcated grouped erythematous, follicular papules on the elbows, knees and over bony prominences.²

Type-V PRP is an atypical generalized juvenile variant which affects 5% of patients. It is a non-remitting hereditary condition with classic characteristics similar to type III with additional scleroderma-like changes involving the palms and soles.²

Diagnosis of PRP is based on clinical recognition and biopsy can be important to secure a diagnosis.

PRP, in many cases is self-limited and asymptomatic, and therefore does not necessarily require treatment. In other patients treatment can be challenging, and referral to a pediatric dermatology specialist is reasonable. Most practitioners recommend combination therapy with topical agents (emollients, topical corticosteroids, tazarotene, topical calcineurin inhibitors, and keratolytic agents such as urea, salicylic acid, or alpha-hydroxy acids) for symptomatic management and systemic therapies (methotrexate, isotretinoin) aimed at reducing inflammation. There is some data that CARD14-associated PRP can respond well to targeted biologic therapies.¹

The subtypes of PRP can present in a myriad of ways and often the disease is misdiagnosed. Depending on the particular subtype and findings present, the differential can vary considerably. Commonly, physicians need to consider: psoriasis, seborrheic dermatitis, atopic dermatitis, ichthyoses, and other conditions which can cause erythroderma.³ The characteristic red-orange color and variable associated edema helps to distinguish keratoderma of PRP from psoriasis, atopic dermatitis, ichthyosis, and hereditary palmoplantar keratoderma. Scalp involvement of PRP should be differentiated from the waxy scale of seborrheic dermatitis and the well demarcated silvery scale of psoriasis. History alone may assist in distinguishing PRP from other major causes of generalized erythroderma, although biopsy is warranted in these cases.
 

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital-San Diego and the University of California, San Diego. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. J Am Acad Dermatol. 2018 Sep;79(3):487-94.

2. “Pityriasis Rubra Pilaris” (Treasure Island, Fla.: StatPearls Publishing, July 20, 2019). 3. JAMA Dermatol. 2016 Jun 1;152(6):670-5.

The Infectious Diseases Society of America (IDSA) recently issued guidelines on the diagnosis of COVID-19.

Courtesy NIAID-RML

These guidelines were developed using a rigorous evidence-based approach, the GRADE framework, which involved identifying the important questions that need to be addressed ahead of time and, later, integrating the best available evidence into the recommendations.

The Food and Drug Administration’s Emergency Use Authorization is useful for understanding any recommendations related to COVID-19 testing. Under usual FDA approval, a manufacturer has to submit data on the performance of a test in human subjects. Under the Emergency Use Authorization for development and approval of SARS-CoV-2 testing, approval is based on “acceptable analytical accuracy,” meaning that a test is assessed using manufactured reagents. The approved test is not tested in real-world clinical situations prior to FDA approval, and the test’s sensitivity and specificity are not well described.

IDSA formulated 15 recommendations, of which the most relevant to primary care clinicians are described and discussed below. The complete set of recommendations can be viewed on the IDSA website:

Recommendation 1

The IDSA panel recommends a SARS-CoV-2 nucleic acid amplification test in symptomatic individuals in the community suspected of having COVID-19, even when the clinical suspicion is low (strong recommendation, very low certainty of evidence). The panel placed a high value on accurate assessment of COVID-19 with the intent of minimizing overdiagnosis of COVID-19 using clinical diagnosis alone. Without testing, the rate of overdiagnosis ranges from 62% to 98%.

If patients are misdiagnosed as having COVID-19, they may spend unnecessary time in quarantine and then may stop taking appropriate safety precautions to protect themselves from infection.

Recommendation 2

The IDSA panel suggests collecting nasopharyngeal, or mid-turbinate or nasal swabs, rather than oropharyngeal swabs or saliva alone for SARS-CoV-2 RNA testing in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, very low certainty of evidence).

The rationale for this recommendation is that comparative data showed a much lower sensitivity for oral sampling, compared with nasopharyngeal, mid-turbinate, or nasal sampling.

The average sensitivity of oral swabs is 56%, compared with nasopharyngeal at 97%, mid-turbinate at 100%, and nasal sampling at 95%. Given these test characteristics, there are far less false-negative tests with nasopharyngeal, mid-turbinate, and nasal swabs. Fewer false negatives means fewer instances of incorrectly telling COVID-19–positive patients that they do not have the illness. An exciting new area of testing that is being evaluated is saliva, which appears to have a sensitivity of 85%.

Recommendation 3

The IDSA panel suggests that nasal and mid-turbinate swab specimens may be collected for SARS-CoV-2 RNA testing by either patients or health care providers in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, low certainty of evidence).

This recommendation is particularly exciting because patient self-collection provides the potential for health care personnel to avoid exposure to infection, as can occur when health care personnel are swabbing a patient; this is ow testing has been done at most testing centers.

While the data are limited, it appears that patient self-collection of nasal or mid-turbinate swabs results in similar detection rates as occurs with health care personnel–collected nasopharyngeal swabs.

Recommendation 6

The IDSA panel suggests repeating viral RNA testing when the initial test is negative (versus performing a single test) in symptomatic individuals with an intermediate or high clinical suspicion of COVID-19 (conditional recommendation, low certainty of evidence).

Since none of the tests are perfect and any can have false negatives, the panel places a high value on detecting infection when present. If there is a low clinical likelihood of disease, the panel recommends not retesting. When the clinical likelihood of COVID-19 is moderate to high, in the event that the initial test is negative, the panel recommends retesting for COVID-19 1-2 days after the initial test.

Recommendation 8

The IDSA panel suggests SARS-CoV-2 RNA testing in asymptomatic individuals who are either known or suspected to have been exposed to COVID-19 (conditional recommendation, very low certainty of evidence).

For this recommendation, a known contact is defined as someone who has had direct contact with a confirmed case.

A suspected exposure occurs when someone is working or living in a congregate setting such as long-term care, a correctional facility, or a cruise ship in which there is an outbreak. The time frame during which to do post-exposure testing is five to seven days after the exposure.

Recommendation 10

The IDSA panel recommends direct SARS-CoV-2 RNA testing in asymptomatic individuals with no known contact with COVID-19 who are being hospitalized in areas with a high prevalence of COVID-19 in the community (conditional recommendation, very low certainty of evidence).

The idea is to do rapid testing to identify individuals entering the hospital either for other illnesses or for procedures, in order to be able to institute appropriate precautions and decrease the likelihood of nosocomial transmission and/or transmission to health care personnel. It is worth noting that the recommendations do not address testing in areas with a low or intermediate prevalence of COVID-19. In the absence of an official guideline-based-recommendation, the decision about testing needs to made by the local hospital system.

Recommendations 11, 12, and 13

The IDSA panel recommends SARS-CoV-2 RNA testing in immunocompromised asymptomatic individuals who are being admitted to the hospital and in asymptomatic individuals prior to receiving immunosuppressive therapy regardless of exposure to COVID-19. It is also recommended to test asymptomatic individuals planning to undergo major surgery.

The rationale for this recommendation is that patients who are to receive chemotherapy, other immunosuppressive procedures, or surgery are at high risk if they have COVID-19 and may be better off delaying the procedure.

Some additional issues were addressed, though not in the form of additional recommendations. It was clarified that some individuals remain nucleic acid positive after their symptoms resolve, and sometimes even after seroconversion. It is not clear if those individuals remain infectious to others. The recommendations did not address serologic testing for public health surveillance.
 

Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

SOURCE: Hanson KE et al. Infectious Diseases Society of America guidelines on the diagnosis of COVID-19.




 

The Infectious Diseases Society of America (IDSA) recently issued guidelines on the diagnosis of COVID-19.

Courtesy NIAID-RML

These guidelines were developed using a rigorous evidence-based approach, the GRADE framework, which involved identifying the important questions that need to be addressed ahead of time and, later, integrating the best available evidence into the recommendations.

The Food and Drug Administration’s Emergency Use Authorization is useful for understanding any recommendations related to COVID-19 testing. Under usual FDA approval, a manufacturer has to submit data on the performance of a test in human subjects. Under the Emergency Use Authorization for development and approval of SARS-CoV-2 testing, approval is based on “acceptable analytical accuracy,” meaning that a test is assessed using manufactured reagents. The approved test is not tested in real-world clinical situations prior to FDA approval, and the test’s sensitivity and specificity are not well described.

IDSA formulated 15 recommendations, of which the most relevant to primary care clinicians are described and discussed below. The complete set of recommendations can be viewed on the IDSA website:

Recommendation 1

The IDSA panel recommends a SARS-CoV-2 nucleic acid amplification test in symptomatic individuals in the community suspected of having COVID-19, even when the clinical suspicion is low (strong recommendation, very low certainty of evidence). The panel placed a high value on accurate assessment of COVID-19 with the intent of minimizing overdiagnosis of COVID-19 using clinical diagnosis alone. Without testing, the rate of overdiagnosis ranges from 62% to 98%.

If patients are misdiagnosed as having COVID-19, they may spend unnecessary time in quarantine and then may stop taking appropriate safety precautions to protect themselves from infection.

Recommendation 2

The IDSA panel suggests collecting nasopharyngeal, or mid-turbinate or nasal swabs, rather than oropharyngeal swabs or saliva alone for SARS-CoV-2 RNA testing in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, very low certainty of evidence).

The rationale for this recommendation is that comparative data showed a much lower sensitivity for oral sampling, compared with nasopharyngeal, mid-turbinate, or nasal sampling.

The average sensitivity of oral swabs is 56%, compared with nasopharyngeal at 97%, mid-turbinate at 100%, and nasal sampling at 95%. Given these test characteristics, there are far less false-negative tests with nasopharyngeal, mid-turbinate, and nasal swabs. Fewer false negatives means fewer instances of incorrectly telling COVID-19–positive patients that they do not have the illness. An exciting new area of testing that is being evaluated is saliva, which appears to have a sensitivity of 85%.

Recommendation 3

The IDSA panel suggests that nasal and mid-turbinate swab specimens may be collected for SARS-CoV-2 RNA testing by either patients or health care providers in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, low certainty of evidence).

This recommendation is particularly exciting because patient self-collection provides the potential for health care personnel to avoid exposure to infection, as can occur when health care personnel are swabbing a patient; this is ow testing has been done at most testing centers.

While the data are limited, it appears that patient self-collection of nasal or mid-turbinate swabs results in similar detection rates as occurs with health care personnel–collected nasopharyngeal swabs.

Recommendation 6

The IDSA panel suggests repeating viral RNA testing when the initial test is negative (versus performing a single test) in symptomatic individuals with an intermediate or high clinical suspicion of COVID-19 (conditional recommendation, low certainty of evidence).

Since none of the tests are perfect and any can have false negatives, the panel places a high value on detecting infection when present. If there is a low clinical likelihood of disease, the panel recommends not retesting. When the clinical likelihood of COVID-19 is moderate to high, in the event that the initial test is negative, the panel recommends retesting for COVID-19 1-2 days after the initial test.

Recommendation 8

The IDSA panel suggests SARS-CoV-2 RNA testing in asymptomatic individuals who are either known or suspected to have been exposed to COVID-19 (conditional recommendation, very low certainty of evidence).

For this recommendation, a known contact is defined as someone who has had direct contact with a confirmed case.

A suspected exposure occurs when someone is working or living in a congregate setting such as long-term care, a correctional facility, or a cruise ship in which there is an outbreak. The time frame during which to do post-exposure testing is five to seven days after the exposure.

Recommendation 10

The IDSA panel recommends direct SARS-CoV-2 RNA testing in asymptomatic individuals with no known contact with COVID-19 who are being hospitalized in areas with a high prevalence of COVID-19 in the community (conditional recommendation, very low certainty of evidence).

The idea is to do rapid testing to identify individuals entering the hospital either for other illnesses or for procedures, in order to be able to institute appropriate precautions and decrease the likelihood of nosocomial transmission and/or transmission to health care personnel. It is worth noting that the recommendations do not address testing in areas with a low or intermediate prevalence of COVID-19. In the absence of an official guideline-based-recommendation, the decision about testing needs to made by the local hospital system.

Recommendations 11, 12, and 13

The IDSA panel recommends SARS-CoV-2 RNA testing in immunocompromised asymptomatic individuals who are being admitted to the hospital and in asymptomatic individuals prior to receiving immunosuppressive therapy regardless of exposure to COVID-19. It is also recommended to test asymptomatic individuals planning to undergo major surgery.

The rationale for this recommendation is that patients who are to receive chemotherapy, other immunosuppressive procedures, or surgery are at high risk if they have COVID-19 and may be better off delaying the procedure.

Some additional issues were addressed, though not in the form of additional recommendations. It was clarified that some individuals remain nucleic acid positive after their symptoms resolve, and sometimes even after seroconversion. It is not clear if those individuals remain infectious to others. The recommendations did not address serologic testing for public health surveillance.
 

Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

SOURCE: Hanson KE et al. Infectious Diseases Society of America guidelines on the diagnosis of COVID-19.




 

The Infectious Diseases Society of America (IDSA) recently issued guidelines on the diagnosis of COVID-19.

Courtesy NIAID-RML

These guidelines were developed using a rigorous evidence-based approach, the GRADE framework, which involved identifying the important questions that need to be addressed ahead of time and, later, integrating the best available evidence into the recommendations.

The Food and Drug Administration’s Emergency Use Authorization is useful for understanding any recommendations related to COVID-19 testing. Under usual FDA approval, a manufacturer has to submit data on the performance of a test in human subjects. Under the Emergency Use Authorization for development and approval of SARS-CoV-2 testing, approval is based on “acceptable analytical accuracy,” meaning that a test is assessed using manufactured reagents. The approved test is not tested in real-world clinical situations prior to FDA approval, and the test’s sensitivity and specificity are not well described.

IDSA formulated 15 recommendations, of which the most relevant to primary care clinicians are described and discussed below. The complete set of recommendations can be viewed on the IDSA website:

Recommendation 1

The IDSA panel recommends a SARS-CoV-2 nucleic acid amplification test in symptomatic individuals in the community suspected of having COVID-19, even when the clinical suspicion is low (strong recommendation, very low certainty of evidence). The panel placed a high value on accurate assessment of COVID-19 with the intent of minimizing overdiagnosis of COVID-19 using clinical diagnosis alone. Without testing, the rate of overdiagnosis ranges from 62% to 98%.

If patients are misdiagnosed as having COVID-19, they may spend unnecessary time in quarantine and then may stop taking appropriate safety precautions to protect themselves from infection.

Recommendation 2

The IDSA panel suggests collecting nasopharyngeal, or mid-turbinate or nasal swabs, rather than oropharyngeal swabs or saliva alone for SARS-CoV-2 RNA testing in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, very low certainty of evidence).

The rationale for this recommendation is that comparative data showed a much lower sensitivity for oral sampling, compared with nasopharyngeal, mid-turbinate, or nasal sampling.

The average sensitivity of oral swabs is 56%, compared with nasopharyngeal at 97%, mid-turbinate at 100%, and nasal sampling at 95%. Given these test characteristics, there are far less false-negative tests with nasopharyngeal, mid-turbinate, and nasal swabs. Fewer false negatives means fewer instances of incorrectly telling COVID-19–positive patients that they do not have the illness. An exciting new area of testing that is being evaluated is saliva, which appears to have a sensitivity of 85%.

Recommendation 3

The IDSA panel suggests that nasal and mid-turbinate swab specimens may be collected for SARS-CoV-2 RNA testing by either patients or health care providers in symptomatic individuals with upper respiratory tract infection or influenza-like illness suspected of having COVID-19 (conditional recommendation, low certainty of evidence).

This recommendation is particularly exciting because patient self-collection provides the potential for health care personnel to avoid exposure to infection, as can occur when health care personnel are swabbing a patient; this is ow testing has been done at most testing centers.

While the data are limited, it appears that patient self-collection of nasal or mid-turbinate swabs results in similar detection rates as occurs with health care personnel–collected nasopharyngeal swabs.

Recommendation 6

The IDSA panel suggests repeating viral RNA testing when the initial test is negative (versus performing a single test) in symptomatic individuals with an intermediate or high clinical suspicion of COVID-19 (conditional recommendation, low certainty of evidence).

Since none of the tests are perfect and any can have false negatives, the panel places a high value on detecting infection when present. If there is a low clinical likelihood of disease, the panel recommends not retesting. When the clinical likelihood of COVID-19 is moderate to high, in the event that the initial test is negative, the panel recommends retesting for COVID-19 1-2 days after the initial test.

Recommendation 8

The IDSA panel suggests SARS-CoV-2 RNA testing in asymptomatic individuals who are either known or suspected to have been exposed to COVID-19 (conditional recommendation, very low certainty of evidence).

For this recommendation, a known contact is defined as someone who has had direct contact with a confirmed case.

A suspected exposure occurs when someone is working or living in a congregate setting such as long-term care, a correctional facility, or a cruise ship in which there is an outbreak. The time frame during which to do post-exposure testing is five to seven days after the exposure.

Recommendation 10

The IDSA panel recommends direct SARS-CoV-2 RNA testing in asymptomatic individuals with no known contact with COVID-19 who are being hospitalized in areas with a high prevalence of COVID-19 in the community (conditional recommendation, very low certainty of evidence).

The idea is to do rapid testing to identify individuals entering the hospital either for other illnesses or for procedures, in order to be able to institute appropriate precautions and decrease the likelihood of nosocomial transmission and/or transmission to health care personnel. It is worth noting that the recommendations do not address testing in areas with a low or intermediate prevalence of COVID-19. In the absence of an official guideline-based-recommendation, the decision about testing needs to made by the local hospital system.

Recommendations 11, 12, and 13

The IDSA panel recommends SARS-CoV-2 RNA testing in immunocompromised asymptomatic individuals who are being admitted to the hospital and in asymptomatic individuals prior to receiving immunosuppressive therapy regardless of exposure to COVID-19. It is also recommended to test asymptomatic individuals planning to undergo major surgery.

The rationale for this recommendation is that patients who are to receive chemotherapy, other immunosuppressive procedures, or surgery are at high risk if they have COVID-19 and may be better off delaying the procedure.

Some additional issues were addressed, though not in the form of additional recommendations. It was clarified that some individuals remain nucleic acid positive after their symptoms resolve, and sometimes even after seroconversion. It is not clear if those individuals remain infectious to others. The recommendations did not address serologic testing for public health surveillance.
 

Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

SOURCE: Hanson KE et al. Infectious Diseases Society of America guidelines on the diagnosis of COVID-19.




 

Over the din of the negative pressure machine, I shouted goodbye to my patient and zipped my way out of one of the little plastic enclosures in our ED and carefully shed my gloves, gown, and face shield, leaving on my precious mask. I discarded the rest with disgust and a bit of fear. I thought, “This is a whole new world, and I hate it.”

I feel as if I am constantly battling the fear of dying from COVID-19 but am doing the best I can, given the circumstances at hand. I have the proper equipment and use it well. My work still brings meaning: I serve those in need without hesitation. The problem is that deep feeling of connection with patients, which is such an important part of this work, feels like fraying threads moving further apart because of the havoc this virus has wrought. A few weeks ago, the intricate fabric of what it is to be human connected me to patients through the basics: touch, facial expressions, a physical proximity, and openhearted, honest dialogue. Much of that’s gone, and while I can carry on, I will surely burn out if I can’t figure out how to get at least some of that connection back.

Overwhelmed by the amount of information I need to process daily, I had not been thinking about the interpersonal side of the pandemic for the first weeks. I felt it leaving the ED that morning and later that day, and I felt it again with Ms. Z, who was not even suspected of having COVID. She is a 62-year-old I interviewed with the help of a translator phone. At the end of our encounter, she said “But doctor, will you make my tumor go away?” From across the room, I said, “I will try.” I saw her eyes dampen as I made a hasty exit, following protocol to limit time in the room of all patients.

Typically, leaving a patient’s room, I would feel a fullness associated with a sense of meaning. How did I feel after that? In that moment, mostly ashamed at my lack of compassion during my time with Ms. Z. Then, with further reflection, tense from all things COVID-19! Having an amped-up sympathetic nervous system is understandable, but it’s not where we want to be for our compassion to flow.

We connect best when our parasympathetic nervous system is predominant. So much of the stimuli we need to activate that part of the nervous system is gone. There is a virtuous cycle, much of it unconscious, where something positive leads to more positivity, which is crucial to meaningful patient encounters. We read each other’s facial expressions, hear the tone of voice, and as we pick up subtle cues from our patient, our nervous system is further engaged and our hearts opened.

The specter of COVID-19 has us battling a negative spiral of stress and fear. For the most part, I try to keep that from consuming me, but it clearly saps my energy during encounters. In the same way we need to marshal our resources to battle both the stress and the disease itself, we need to actively engage pro-social elements of providing care to maintain our compassion. Clearly, I needed a more concerted effort to kick start this virtuous cycle of compassion.

My next patient was Ms. J., a 55-year-old with advanced chronic obstructive pulmonary disease (COPD) who came in the night before with shortness of breath. Her slight frame shook from coughing as I entered the room. I did not think she had COVID-19, but we were ruling it out.

We reviewed how she felt since admission, and I performed a hasty exam and stepped back across the room. She coughed again and said, “I feel so weak, and the world feels so crazy; tell it to me straight.” Then looking in my eyes, “I am going to make it, doc?”

I took my cue from her; I walked back to the bedside, placed a gloved hand on her shoulder and with the other, I took her hand. I bent forward just a little. Making eye contact and attempting a comforting tone of voice, I said, “Everyone is a little scared, including me. We need each other more than ever these days. We will do our best for you. That means thoughtful medical care and a whole lot of love! And, truly, I don’t think you are dying; this is just one of your COPD flares.”

“God bless you!” she said, squeezing my hand as a tear rolled down her cheek.

“Bless you, too. We all need blessing with this madness going on,” I replied. Despite the mask, I am sure she saw the smile in my eyes. “Thanks for being the beautiful person you are and opening up to me. That’s the way we will make it through this. I will see you tomorrow.” Backing away, hands together in prayer, I gave a little bow and left the room.

With Ms. J.’s help, I began to figure it out. To tackle the stress of COVID, we need to be very direct – almost to the point of exaggeration – to make sure our words and actions convey what we need to express. William James, the father of psychology, believed that if you force a smile, your emotions would follow. The neural pathways could work backward in that way. He said, “If you want a quality, act as if you have it.” The modern translation would be, “Fake it ’til you make it.’ ” You may be feeling stressed, but with a deep breath and a moment’s reflection on the suffering of that patient you are about to see, you can turn the tide on anxiety and give those under your care what they need.

These are unprecedented times; anxiety abounds. While we can aspire to positivity, there are times when we simply can’t muster showing it. Alternatively, as I experienced with Ms. J., honesty and vulnerability can open the door to meaningful connection. This can be quite powerful when we, as physicians, open up to our patients.

People are yearning for deep connection, and we should attempt to deliver it with:

• Touch (as we can) to convey connection.
• Body language that adds emphasis to our message and our emotions that may go above and beyond what we are used to.
• Tone of voice that enhances our words.
• Talk that emphasizes the big stuff, such as love, fear, connection and community

With gloves, masks, distance, and fear between and us and our patients, we need to actively engage our pro-social tools to turn the negative spiral of fear into the virtuous cycle of positive emotions that promotes healing of our patients and emotional engagement for those providing their care.
 

Dr. Hass was trained in family medicine at University of California, San Francisco, after receiving his medical degree from the McGill University faculty of medicine, Montreal. He works as a hospitalist with Sutter Health in Oakland, Calif. He is an adviser on health and health care for the Greater Good Science Center at UC Berkeley and clinical faculty at UCSF School of Medicine. This article appeared initially at The Hospital Leader, the official blog of SHM.

Over the din of the negative pressure machine, I shouted goodbye to my patient and zipped my way out of one of the little plastic enclosures in our ED and carefully shed my gloves, gown, and face shield, leaving on my precious mask. I discarded the rest with disgust and a bit of fear. I thought, “This is a whole new world, and I hate it.”

I feel as if I am constantly battling the fear of dying from COVID-19 but am doing the best I can, given the circumstances at hand. I have the proper equipment and use it well. My work still brings meaning: I serve those in need without hesitation. The problem is that deep feeling of connection with patients, which is such an important part of this work, feels like fraying threads moving further apart because of the havoc this virus has wrought. A few weeks ago, the intricate fabric of what it is to be human connected me to patients through the basics: touch, facial expressions, a physical proximity, and openhearted, honest dialogue. Much of that’s gone, and while I can carry on, I will surely burn out if I can’t figure out how to get at least some of that connection back.

Overwhelmed by the amount of information I need to process daily, I had not been thinking about the interpersonal side of the pandemic for the first weeks. I felt it leaving the ED that morning and later that day, and I felt it again with Ms. Z, who was not even suspected of having COVID. She is a 62-year-old I interviewed with the help of a translator phone. At the end of our encounter, she said “But doctor, will you make my tumor go away?” From across the room, I said, “I will try.” I saw her eyes dampen as I made a hasty exit, following protocol to limit time in the room of all patients.

Typically, leaving a patient’s room, I would feel a fullness associated with a sense of meaning. How did I feel after that? In that moment, mostly ashamed at my lack of compassion during my time with Ms. Z. Then, with further reflection, tense from all things COVID-19! Having an amped-up sympathetic nervous system is understandable, but it’s not where we want to be for our compassion to flow.

We connect best when our parasympathetic nervous system is predominant. So much of the stimuli we need to activate that part of the nervous system is gone. There is a virtuous cycle, much of it unconscious, where something positive leads to more positivity, which is crucial to meaningful patient encounters. We read each other’s facial expressions, hear the tone of voice, and as we pick up subtle cues from our patient, our nervous system is further engaged and our hearts opened.

The specter of COVID-19 has us battling a negative spiral of stress and fear. For the most part, I try to keep that from consuming me, but it clearly saps my energy during encounters. In the same way we need to marshal our resources to battle both the stress and the disease itself, we need to actively engage pro-social elements of providing care to maintain our compassion. Clearly, I needed a more concerted effort to kick start this virtuous cycle of compassion.

My next patient was Ms. J., a 55-year-old with advanced chronic obstructive pulmonary disease (COPD) who came in the night before with shortness of breath. Her slight frame shook from coughing as I entered the room. I did not think she had COVID-19, but we were ruling it out.

We reviewed how she felt since admission, and I performed a hasty exam and stepped back across the room. She coughed again and said, “I feel so weak, and the world feels so crazy; tell it to me straight.” Then looking in my eyes, “I am going to make it, doc?”

I took my cue from her; I walked back to the bedside, placed a gloved hand on her shoulder and with the other, I took her hand. I bent forward just a little. Making eye contact and attempting a comforting tone of voice, I said, “Everyone is a little scared, including me. We need each other more than ever these days. We will do our best for you. That means thoughtful medical care and a whole lot of love! And, truly, I don’t think you are dying; this is just one of your COPD flares.”

“God bless you!” she said, squeezing my hand as a tear rolled down her cheek.

“Bless you, too. We all need blessing with this madness going on,” I replied. Despite the mask, I am sure she saw the smile in my eyes. “Thanks for being the beautiful person you are and opening up to me. That’s the way we will make it through this. I will see you tomorrow.” Backing away, hands together in prayer, I gave a little bow and left the room.

With Ms. J.’s help, I began to figure it out. To tackle the stress of COVID, we need to be very direct – almost to the point of exaggeration – to make sure our words and actions convey what we need to express. William James, the father of psychology, believed that if you force a smile, your emotions would follow. The neural pathways could work backward in that way. He said, “If you want a quality, act as if you have it.” The modern translation would be, “Fake it ’til you make it.’ ” You may be feeling stressed, but with a deep breath and a moment’s reflection on the suffering of that patient you are about to see, you can turn the tide on anxiety and give those under your care what they need.

These are unprecedented times; anxiety abounds. While we can aspire to positivity, there are times when we simply can’t muster showing it. Alternatively, as I experienced with Ms. J., honesty and vulnerability can open the door to meaningful connection. This can be quite powerful when we, as physicians, open up to our patients.

People are yearning for deep connection, and we should attempt to deliver it with:

• Touch (as we can) to convey connection.
• Body language that adds emphasis to our message and our emotions that may go above and beyond what we are used to.
• Tone of voice that enhances our words.
• Talk that emphasizes the big stuff, such as love, fear, connection and community

With gloves, masks, distance, and fear between and us and our patients, we need to actively engage our pro-social tools to turn the negative spiral of fear into the virtuous cycle of positive emotions that promotes healing of our patients and emotional engagement for those providing their care.
 

Dr. Hass was trained in family medicine at University of California, San Francisco, after receiving his medical degree from the McGill University faculty of medicine, Montreal. He works as a hospitalist with Sutter Health in Oakland, Calif. He is an adviser on health and health care for the Greater Good Science Center at UC Berkeley and clinical faculty at UCSF School of Medicine. This article appeared initially at The Hospital Leader, the official blog of SHM.

Over the din of the negative pressure machine, I shouted goodbye to my patient and zipped my way out of one of the little plastic enclosures in our ED and carefully shed my gloves, gown, and face shield, leaving on my precious mask. I discarded the rest with disgust and a bit of fear. I thought, “This is a whole new world, and I hate it.”

I feel as if I am constantly battling the fear of dying from COVID-19 but am doing the best I can, given the circumstances at hand. I have the proper equipment and use it well. My work still brings meaning: I serve those in need without hesitation. The problem is that deep feeling of connection with patients, which is such an important part of this work, feels like fraying threads moving further apart because of the havoc this virus has wrought. A few weeks ago, the intricate fabric of what it is to be human connected me to patients through the basics: touch, facial expressions, a physical proximity, and openhearted, honest dialogue. Much of that’s gone, and while I can carry on, I will surely burn out if I can’t figure out how to get at least some of that connection back.

Overwhelmed by the amount of information I need to process daily, I had not been thinking about the interpersonal side of the pandemic for the first weeks. I felt it leaving the ED that morning and later that day, and I felt it again with Ms. Z, who was not even suspected of having COVID. She is a 62-year-old I interviewed with the help of a translator phone. At the end of our encounter, she said “But doctor, will you make my tumor go away?” From across the room, I said, “I will try.” I saw her eyes dampen as I made a hasty exit, following protocol to limit time in the room of all patients.

Typically, leaving a patient’s room, I would feel a fullness associated with a sense of meaning. How did I feel after that? In that moment, mostly ashamed at my lack of compassion during my time with Ms. Z. Then, with further reflection, tense from all things COVID-19! Having an amped-up sympathetic nervous system is understandable, but it’s not where we want to be for our compassion to flow.

We connect best when our parasympathetic nervous system is predominant. So much of the stimuli we need to activate that part of the nervous system is gone. There is a virtuous cycle, much of it unconscious, where something positive leads to more positivity, which is crucial to meaningful patient encounters. We read each other’s facial expressions, hear the tone of voice, and as we pick up subtle cues from our patient, our nervous system is further engaged and our hearts opened.

The specter of COVID-19 has us battling a negative spiral of stress and fear. For the most part, I try to keep that from consuming me, but it clearly saps my energy during encounters. In the same way we need to marshal our resources to battle both the stress and the disease itself, we need to actively engage pro-social elements of providing care to maintain our compassion. Clearly, I needed a more concerted effort to kick start this virtuous cycle of compassion.

My next patient was Ms. J., a 55-year-old with advanced chronic obstructive pulmonary disease (COPD) who came in the night before with shortness of breath. Her slight frame shook from coughing as I entered the room. I did not think she had COVID-19, but we were ruling it out.

We reviewed how she felt since admission, and I performed a hasty exam and stepped back across the room. She coughed again and said, “I feel so weak, and the world feels so crazy; tell it to me straight.” Then looking in my eyes, “I am going to make it, doc?”

I took my cue from her; I walked back to the bedside, placed a gloved hand on her shoulder and with the other, I took her hand. I bent forward just a little. Making eye contact and attempting a comforting tone of voice, I said, “Everyone is a little scared, including me. We need each other more than ever these days. We will do our best for you. That means thoughtful medical care and a whole lot of love! And, truly, I don’t think you are dying; this is just one of your COPD flares.”

“God bless you!” she said, squeezing my hand as a tear rolled down her cheek.

“Bless you, too. We all need blessing with this madness going on,” I replied. Despite the mask, I am sure she saw the smile in my eyes. “Thanks for being the beautiful person you are and opening up to me. That’s the way we will make it through this. I will see you tomorrow.” Backing away, hands together in prayer, I gave a little bow and left the room.

With Ms. J.’s help, I began to figure it out. To tackle the stress of COVID, we need to be very direct – almost to the point of exaggeration – to make sure our words and actions convey what we need to express. William James, the father of psychology, believed that if you force a smile, your emotions would follow. The neural pathways could work backward in that way. He said, “If you want a quality, act as if you have it.” The modern translation would be, “Fake it ’til you make it.’ ” You may be feeling stressed, but with a deep breath and a moment’s reflection on the suffering of that patient you are about to see, you can turn the tide on anxiety and give those under your care what they need.

These are unprecedented times; anxiety abounds. While we can aspire to positivity, there are times when we simply can’t muster showing it. Alternatively, as I experienced with Ms. J., honesty and vulnerability can open the door to meaningful connection. This can be quite powerful when we, as physicians, open up to our patients.

People are yearning for deep connection, and we should attempt to deliver it with:

• Touch (as we can) to convey connection.
• Body language that adds emphasis to our message and our emotions that may go above and beyond what we are used to.
• Tone of voice that enhances our words.
• Talk that emphasizes the big stuff, such as love, fear, connection and community

With gloves, masks, distance, and fear between and us and our patients, we need to actively engage our pro-social tools to turn the negative spiral of fear into the virtuous cycle of positive emotions that promotes healing of our patients and emotional engagement for those providing their care.
 

Dr. Hass was trained in family medicine at University of California, San Francisco, after receiving his medical degree from the McGill University faculty of medicine, Montreal. He works as a hospitalist with Sutter Health in Oakland, Calif. He is an adviser on health and health care for the Greater Good Science Center at UC Berkeley and clinical faculty at UCSF School of Medicine. This article appeared initially at The Hospital Leader, the official blog of SHM.

Kawasaki disease

Given the presentation of persistent fever, nonpurulent conjunctivitis, cracked lips, erythematous tongue, desquamating perianal rash, and acral edema and erythema, suspicion was high for Kawasaki disease (KD). An echocardiogram revealed diffuse dilation of the left anterior descending artery without evidence of an aneurysm. The patient was promptly started on 2 g/kg IVIG and high-dose aspirin. She was later transitioned to low-dose aspirin. Long-term follow-up thus far has revealed no cardiac sequelae.

KD, or mucocutaneous lymph node syndrome, is a multisystem vasculitis with predilection for the coronary arteries that most commonly affects children between 6 months and 5 years of age.¹ While the etiology remains unclear, the pathogenesis is thought to be the result of an immune response to an infection in the setting of genetic susceptibility.¹ Approximately 90% of patients have mucocutaneous manifestations, highlighting the important role dermatologists play in the diagnosis and early intervention to prevent cardiovascular morbidity.

The diagnostic criteria include fever for at least 5 days accompanied by at least four of the following:

• Bilateral bulbar conjunctival injection without exudate that is classically limbal sparing.
• Oral mucosal changes with cracked fissured lips, “strawberry tongue,” or erythema of the lips and mucosa.
• Changes in the extremities: erythema, swelling, or periungual peeling.
• Polymorphous exanthem.
• Cervical lymphadenopathy, often unilateral (greater than 1.5 cm).

Courtesy Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, department of dermatology at the University of Rochester (N.Y.)

Although nonspecific for diagnosis, laboratory abnormalities are common, including anemia, thrombocytosis, leukocytosis, elevated inflammatory markers, elevated alanine aminotransferase (ALT), hypoalbuminemia, and sterile pyuria on urine analysis.¹

Notably, a classic finding of KD is perineal dermatitis with desquamation occurring in the acute phase of disease in 80%-90% of patients.^2-5 In a retrospective review, up to 67% of patients with KD developed a perineal rash in the first week, most often beginning in the diaper area.² The perineal rash classically desquamates early during the acute phase of the disease.¹

While most individuals with KD follow a benign disease course, it is the most common cause of acquired heart disease in the United States.¹ Treatment is aimed at decreasing the risk of developing coronary abnormalities through the prompt administration of IVIG and high-dose aspirin initiated early in the acute phase.⁶ A second dose of IVIG may be given to patients who remain febrile within 24-48 hours after treatment.⁶ Infliximab has been used safely and effectively in patients with refractory KD.⁷ Long-term cardiac follow-up of KD patients is recommended.

Recently, there has been an emerging association between COVID-19 and pediatric multi-system inflammatory syndrome, which shares features with KD. Patients with pediatric multi-system inflammatory syndrome who meet clinical criteria for KD should be promptly treated with IVIG and aspirin to avoid long-term cardiac sequelae.

This case and the photos were submitted by Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, both with the department of dermatology at the University of Rochester (N.Y.). Dr. Donna Bilu Martin edited the case.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bayers S et al. (2013). J Am Acad Dermatol. 2013 Oct;69(4):501.e1-11.

2. Friter BS and Lucky AW. Arch Dermatol. 1988 Dec;124(12):1805-10.

3. Urbach AH et al. Am J Dis Child. 1988 Nov;142(11):1174-6.

4. Fink CW. Pediatr Infect Dis. 1983 Mar-Apr; 2(2):140-1.

5. Aballi A J and Bisken LC. Pediatr Infect Dis. 1984 Mar-Apr;3(2):187.

6. McCrindle BW et al. Circulation. 2017 Apr 25;135(17):e927-e99.

7.Sauvaget E et al. J Pediatr. 2012 May; 160(5),875-6.


 

Kawasaki disease

Given the presentation of persistent fever, nonpurulent conjunctivitis, cracked lips, erythematous tongue, desquamating perianal rash, and acral edema and erythema, suspicion was high for Kawasaki disease (KD). An echocardiogram revealed diffuse dilation of the left anterior descending artery without evidence of an aneurysm. The patient was promptly started on 2 g/kg IVIG and high-dose aspirin. She was later transitioned to low-dose aspirin. Long-term follow-up thus far has revealed no cardiac sequelae.

KD, or mucocutaneous lymph node syndrome, is a multisystem vasculitis with predilection for the coronary arteries that most commonly affects children between 6 months and 5 years of age.¹ While the etiology remains unclear, the pathogenesis is thought to be the result of an immune response to an infection in the setting of genetic susceptibility.¹ Approximately 90% of patients have mucocutaneous manifestations, highlighting the important role dermatologists play in the diagnosis and early intervention to prevent cardiovascular morbidity.

The diagnostic criteria include fever for at least 5 days accompanied by at least four of the following:

• Bilateral bulbar conjunctival injection without exudate that is classically limbal sparing.
• Oral mucosal changes with cracked fissured lips, “strawberry tongue,” or erythema of the lips and mucosa.
• Changes in the extremities: erythema, swelling, or periungual peeling.
• Polymorphous exanthem.
• Cervical lymphadenopathy, often unilateral (greater than 1.5 cm).

Courtesy Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, department of dermatology at the University of Rochester (N.Y.)

Although nonspecific for diagnosis, laboratory abnormalities are common, including anemia, thrombocytosis, leukocytosis, elevated inflammatory markers, elevated alanine aminotransferase (ALT), hypoalbuminemia, and sterile pyuria on urine analysis.¹

Notably, a classic finding of KD is perineal dermatitis with desquamation occurring in the acute phase of disease in 80%-90% of patients.^2-5 In a retrospective review, up to 67% of patients with KD developed a perineal rash in the first week, most often beginning in the diaper area.² The perineal rash classically desquamates early during the acute phase of the disease.¹

While most individuals with KD follow a benign disease course, it is the most common cause of acquired heart disease in the United States.¹ Treatment is aimed at decreasing the risk of developing coronary abnormalities through the prompt administration of IVIG and high-dose aspirin initiated early in the acute phase.⁶ A second dose of IVIG may be given to patients who remain febrile within 24-48 hours after treatment.⁶ Infliximab has been used safely and effectively in patients with refractory KD.⁷ Long-term cardiac follow-up of KD patients is recommended.

Recently, there has been an emerging association between COVID-19 and pediatric multi-system inflammatory syndrome, which shares features with KD. Patients with pediatric multi-system inflammatory syndrome who meet clinical criteria for KD should be promptly treated with IVIG and aspirin to avoid long-term cardiac sequelae.

This case and the photos were submitted by Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, both with the department of dermatology at the University of Rochester (N.Y.). Dr. Donna Bilu Martin edited the case.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bayers S et al. (2013). J Am Acad Dermatol. 2013 Oct;69(4):501.e1-11.

2. Friter BS and Lucky AW. Arch Dermatol. 1988 Dec;124(12):1805-10.

3. Urbach AH et al. Am J Dis Child. 1988 Nov;142(11):1174-6.

4. Fink CW. Pediatr Infect Dis. 1983 Mar-Apr; 2(2):140-1.

5. Aballi A J and Bisken LC. Pediatr Infect Dis. 1984 Mar-Apr;3(2):187.

6. McCrindle BW et al. Circulation. 2017 Apr 25;135(17):e927-e99.

7.Sauvaget E et al. J Pediatr. 2012 May; 160(5),875-6.


 

Kawasaki disease

Given the presentation of persistent fever, nonpurulent conjunctivitis, cracked lips, erythematous tongue, desquamating perianal rash, and acral edema and erythema, suspicion was high for Kawasaki disease (KD). An echocardiogram revealed diffuse dilation of the left anterior descending artery without evidence of an aneurysm. The patient was promptly started on 2 g/kg IVIG and high-dose aspirin. She was later transitioned to low-dose aspirin. Long-term follow-up thus far has revealed no cardiac sequelae.

KD, or mucocutaneous lymph node syndrome, is a multisystem vasculitis with predilection for the coronary arteries that most commonly affects children between 6 months and 5 years of age.¹ While the etiology remains unclear, the pathogenesis is thought to be the result of an immune response to an infection in the setting of genetic susceptibility.¹ Approximately 90% of patients have mucocutaneous manifestations, highlighting the important role dermatologists play in the diagnosis and early intervention to prevent cardiovascular morbidity.

The diagnostic criteria include fever for at least 5 days accompanied by at least four of the following:

• Bilateral bulbar conjunctival injection without exudate that is classically limbal sparing.
• Oral mucosal changes with cracked fissured lips, “strawberry tongue,” or erythema of the lips and mucosa.
• Changes in the extremities: erythema, swelling, or periungual peeling.
• Polymorphous exanthem.
• Cervical lymphadenopathy, often unilateral (greater than 1.5 cm).

Courtesy Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, department of dermatology at the University of Rochester (N.Y.)

Although nonspecific for diagnosis, laboratory abnormalities are common, including anemia, thrombocytosis, leukocytosis, elevated inflammatory markers, elevated alanine aminotransferase (ALT), hypoalbuminemia, and sterile pyuria on urine analysis.¹

Notably, a classic finding of KD is perineal dermatitis with desquamation occurring in the acute phase of disease in 80%-90% of patients.^2-5 In a retrospective review, up to 67% of patients with KD developed a perineal rash in the first week, most often beginning in the diaper area.² The perineal rash classically desquamates early during the acute phase of the disease.¹

While most individuals with KD follow a benign disease course, it is the most common cause of acquired heart disease in the United States.¹ Treatment is aimed at decreasing the risk of developing coronary abnormalities through the prompt administration of IVIG and high-dose aspirin initiated early in the acute phase.⁶ A second dose of IVIG may be given to patients who remain febrile within 24-48 hours after treatment.⁶ Infliximab has been used safely and effectively in patients with refractory KD.⁷ Long-term cardiac follow-up of KD patients is recommended.

Recently, there has been an emerging association between COVID-19 and pediatric multi-system inflammatory syndrome, which shares features with KD. Patients with pediatric multi-system inflammatory syndrome who meet clinical criteria for KD should be promptly treated with IVIG and aspirin to avoid long-term cardiac sequelae.

This case and the photos were submitted by Dr. Elizabeth H. Cusick and Dr. Molly E. Plovanich, both with the department of dermatology at the University of Rochester (N.Y.). Dr. Donna Bilu Martin edited the case.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Bayers S et al. (2013). J Am Acad Dermatol. 2013 Oct;69(4):501.e1-11.

2. Friter BS and Lucky AW. Arch Dermatol. 1988 Dec;124(12):1805-10.

3. Urbach AH et al. Am J Dis Child. 1988 Nov;142(11):1174-6.

4. Fink CW. Pediatr Infect Dis. 1983 Mar-Apr; 2(2):140-1.

5. Aballi A J and Bisken LC. Pediatr Infect Dis. 1984 Mar-Apr;3(2):187.

6. McCrindle BW et al. Circulation. 2017 Apr 25;135(17):e927-e99.

7.Sauvaget E et al. J Pediatr. 2012 May; 160(5),875-6.


 

To the Editor: I am very disappointed to continue receiving my copies of the Federal Practitioner in nonrecyclable plastic. As a health care professional, I am on the mailing list for numerous other medical publications, all of which seem to be able to utilize recyclable plastic wrappers. I hope you can rectify this problem, which is an embarrassment to me, a serviceconnected veteran.

C. William Kaiser, MD 

To the Editor: I am very disappointed to continue receiving my copies of the Federal Practitioner in nonrecyclable plastic. As a health care professional, I am on the mailing list for numerous other medical publications, all of which seem to be able to utilize recyclable plastic wrappers. I hope you can rectify this problem, which is an embarrassment to me, a serviceconnected veteran.

C. William Kaiser, MD 

To the Editor: I am very disappointed to continue receiving my copies of the Federal Practitioner in nonrecyclable plastic. As a health care professional, I am on the mailing list for numerous other medical publications, all of which seem to be able to utilize recyclable plastic wrappers. I hope you can rectify this problem, which is an embarrassment to me, a serviceconnected veteran.

C. William Kaiser, MD 

We are living through unprecedented challenges, faced with profound uncertainties about the public health, the economy, the safety of our workplaces, the risks of gathering with friends and family, and even about the rhythm of the school year. Parents always have sought guidance from their pediatric providers when they are uncertain about their children’s health, behavior, and development. We want to share some guidance with you about several of the most common questions we have been hearing in the past few months, in the hope that it may prove useful in your conversations with patients and families.

ArtMarie/E+

What happens when we are so busy at home that our 2-year-old is ignored for much of the day?

If they are fortunate enough to be able to work from home, but have lost their child care, many parents are suddenly facing the sustained challenge of parenting while working. Even older children will have a tough time remembering that home is now a workplace, and they can’t interrupt their parents during a Zoom meeting. But older children will understand. Younger children (preschoolers) simply will not be able to understand that their parents are in sight but not fully available to them. They are exquisitely sensitive to their parents’ attention. If they are consistently ignored, behavioral problems can emerge. If both parents are at home, they should try to arrange a schedule taking turns so that one of them could turn their full attention to their kids if need be. If a working parent can be out of sight (i.e., in another room), it makes the situation easier for everyone.

If there is only one parent at home, that mom or dad should consider arranging a babysitter or sharing child care with a friend, with some reasonable safety provisions in place. The small risk of exposure to the virus is balanced by the risk of sustained invalidation in a developing child. Help parents set reasonable expectations for how productive they can be at home. If possible, they can manage their employer’s expectations, so that they do not find themselves in the impossible bind of choosing between a crying child and a crucial deadline. If they can work near the child (and be prepared for interruptions) when reading emails or writing, that may be enough availability for the child. And parents should not be discouraged when they have to repeatedly remind their children that they adore them, but also have to work while they are at home right now. Using age-appropriate screen time as a babysitter for a few hours each day is a perfectly acceptable part of a plan. Simply planning regular breaks when their children can have their attention will make the day easier for everyone at home.
 

What can I do about my 13-year-old who is lying around the house all day?

This is a time to pick your battles. If children can keep their regular sleep schedule, get their schoolwork done, and do some physical exercise every day, they are doing great. And if parents are continuously complaining that they are being lazy, it will probably cease to mean much to them. Instead, focus on clear, simple expectations, and parents should live by them, too. If parents can exercise with them, or try a new activity, that is a wonderful way to model self-care and trying new things. It is important to remember that the developmental task for a 13-year-old is to establish new avenues of independence that they will drive down further with each passing year. Give them some leeway to experiment and figure out their own way of handling this challenge, although it is bound to create some tension. Parents should always acknowledge how hard it is to stick with schoolwork without school, exercise without a team, practice music without a band, or do your work without an office!

What do we do about our 16-year-old who is staying up all night and sleeping until the late afternoon?

Adolescents naturally have their sleep cycle shift, so they are sleepy later and sleep longer. But staying up all night is usually about texting with friends or playing video games. The problem is that their sleep schedule can flip. They will not be able to participate in online class or enjoy exercise in the sun, and they rarely get enough sleep during the daytime, making them more irritable, anxious, inattentive, and tired. This will only make managing their schoolwork harder and increase the chances of conflict at home. So it is important to preserve rules around sleep. You might extend bedtime by an hour or so, but preserve rules and bedtime routines. Sleep is essential to health, well-being, and resilience, and all are critical during times of uncertainty and change.

We think our 17-year-old is using marijuana, and it might be a problem.

When parents think their children may have a problem with drugs, the children almost certainly do, as parents are typically the last to know about the extent of their use. Sheltering in place together may make their drug use much more apparent, and offer an opportunity for parents to respond. Talk with them about it. Let them know what you have noticed. See if they can tell you honestly about their drug use. Kids who are only experimenting socially are unlikely to be using drugs at home under quarantine. If you are truly calm and curious, they are more likely to be honest, and it could be a relief for them to discuss it with you. Find out what they think it helps, and what – if anything – they are worried about. Then share your concerns about marijuana use and the developing brain, and the risk of addiction. If they think it is “medical” use, remind them that anxiety or mood symptoms get better with therapy, whereas drugs (including marijuana) and alcohol actually worsen those problems. It is also a time to establish home rules, explain them, and enforce them. They will have your support while stopping and may learn that they are actually sleeping and feeling better after a few weeks without marijuana.

Parents should not hesitate to reach out to pediatric providers for guidance on local resources for assessment and treatment for substance abuse and addiction. These are medical problems, and they can become serious if untreated.

My 12-year-old perfectionist is very stressed about getting her work done well now that she is home schooling. How do I help her relax?

Some children, especially our anxious perfectionists, may respond to the switch to home school with great effort and organization. These kids usually are not the ones parents worry about. But they are very prone to expanding anxiety without the regular support and feedback of teachers. The school environment naturally encourages their taking chances and normalizes the setbacks and failures that are an essential part of learning something new. At home, parents are inclined to let these kids work independently. But they benefit from regular check-ins that are not focused on work completion or scores. Instead, ask about what they are doing that is hardest, and let them teach you about it. Model how you approach a new challenge, and how you regroup and try again when you don’t get it right. Finally, this is a good age to start discussing “reasonable expectations.” No one can “do their best” all the time; not parents, not professional athletes, not even machines can sustain long bursts of maximum speed without problems. Help them to start experimenting with different speeds and levels of effort, and see how it feels.

My 10-year-old is very anxious about catching coronavirus or one of us catching it. How do I help ease her anxiety when there is no certainty about how to prevent it?

Anxiety is a normal response to a situation with as much uncertainty as this one. But some are prone to more profound anxiety, and parents may find they are doing a lot of reassuring throughout the day. For especially anxious children (and adults), accommodating the anxiety by avoiding the stressful situation is a common response that provides temporary relief. But accommodation and avoidance actually fuel anxiety, and make it harder and harder to manage. It is important to talk about the “accommodations” we all are doing, how masks are recommended to protect others (not ourselves) and to slow down the spread of a new illness so our hospitals aren’t overwhelmed. It can seem counterintuitive, but rather than jumping to reassurance or dismissing their sense of risk, ask your children to play the full movie of what they are most worried about. What happens if they get sick? If you get sick? If they are worried about dying, go ahead and ask what they think happens then. You are demonstrating that you have confidence they can handle these feelings, and you are modeling curiosity – not avoidance – yourself. Correct any misunderstandings, check on facts together, acknowledge uncertainty. It also is very important for parents to assess whether their own anxiety level makes this task especially hard or may even be contributing to their children’s level of worry. Each of us is managing anxiety right now, and this moment presents an opportunity for all of us to learn about how we can face and bear it, learn to manage, and even master it.

We are all getting cabin fever at home and snapping at each other constantly. How do we keep the peace without just hiding in our rooms all day?

Cabin fever seems inevitable when a family is suddenly at home together all day every day with no end in sight. But if we establish some simple and realistic routines and preserve some structure without being rigid, it can go a long way to helping each member of a family to find their equilibrium in this new normal. Structure can be about preserving normal sleep and meal times. Ensuring everyone is getting adequate, restful sleep and is not hungry is probably the most powerful way to keep irritability and conflict low. It is also helpful to establish some new routines. These should be simple enough to be memorable and should be realistic. You might identify predictable blocks of time that are dedicated to school (or work), exercise, creative time, and family time. While much of the day may find each family member doing some independent activity, it helps when these “blocks” are the same for everybody. Try to consistently do one or two things together, like a walk after the family dinner or family game time. And also remember that everyone needs some alone time. Respect their need for this, and it will help you to explain when you need it. If someone wants to sit out the family Yahtzee tournament, don’t shame or punish them. Just invite them again the next night!

What are going to be the consequences of all this screen time?

The great majority of kids (and parents) will not suffer any adverse consequences from the increased amount of time spent in front of screens when these activities are varied and serve a useful purpose – including distraction, senseless fun, and social time. Beyond letter or email writing, screen and phone time are the only ways to stay socially connected while physically distant. But parents are the experts on their kids. Youth who are depressed and have in the past wanted to escape into long hours of video games or YouTube videos should not be allowed to do that now. Youth with attentional issues who have a hard time stopping video games will still have that difficulty. If they are getting adequate sleep and regular exercise, and are doing most of their school work and staying socially connected, screens are not dangerous. They are proving to be a wonderful tool to help us visit libraries and museums, take dance classes, learn new languages, follow the news, order groceries, or enjoy a movie together. If we stay connected to those we care about and to the world, then this time – although marked by profound suffering and loss – may prove to be a time when we were able to slow down and remember what truly matters in our lives.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

We are living through unprecedented challenges, faced with profound uncertainties about the public health, the economy, the safety of our workplaces, the risks of gathering with friends and family, and even about the rhythm of the school year. Parents always have sought guidance from their pediatric providers when they are uncertain about their children’s health, behavior, and development. We want to share some guidance with you about several of the most common questions we have been hearing in the past few months, in the hope that it may prove useful in your conversations with patients and families.

ArtMarie/E+

What happens when we are so busy at home that our 2-year-old is ignored for much of the day?

If they are fortunate enough to be able to work from home, but have lost their child care, many parents are suddenly facing the sustained challenge of parenting while working. Even older children will have a tough time remembering that home is now a workplace, and they can’t interrupt their parents during a Zoom meeting. But older children will understand. Younger children (preschoolers) simply will not be able to understand that their parents are in sight but not fully available to them. They are exquisitely sensitive to their parents’ attention. If they are consistently ignored, behavioral problems can emerge. If both parents are at home, they should try to arrange a schedule taking turns so that one of them could turn their full attention to their kids if need be. If a working parent can be out of sight (i.e., in another room), it makes the situation easier for everyone.

If there is only one parent at home, that mom or dad should consider arranging a babysitter or sharing child care with a friend, with some reasonable safety provisions in place. The small risk of exposure to the virus is balanced by the risk of sustained invalidation in a developing child. Help parents set reasonable expectations for how productive they can be at home. If possible, they can manage their employer’s expectations, so that they do not find themselves in the impossible bind of choosing between a crying child and a crucial deadline. If they can work near the child (and be prepared for interruptions) when reading emails or writing, that may be enough availability for the child. And parents should not be discouraged when they have to repeatedly remind their children that they adore them, but also have to work while they are at home right now. Using age-appropriate screen time as a babysitter for a few hours each day is a perfectly acceptable part of a plan. Simply planning regular breaks when their children can have their attention will make the day easier for everyone at home.
 

What can I do about my 13-year-old who is lying around the house all day?

This is a time to pick your battles. If children can keep their regular sleep schedule, get their schoolwork done, and do some physical exercise every day, they are doing great. And if parents are continuously complaining that they are being lazy, it will probably cease to mean much to them. Instead, focus on clear, simple expectations, and parents should live by them, too. If parents can exercise with them, or try a new activity, that is a wonderful way to model self-care and trying new things. It is important to remember that the developmental task for a 13-year-old is to establish new avenues of independence that they will drive down further with each passing year. Give them some leeway to experiment and figure out their own way of handling this challenge, although it is bound to create some tension. Parents should always acknowledge how hard it is to stick with schoolwork without school, exercise without a team, practice music without a band, or do your work without an office!

What do we do about our 16-year-old who is staying up all night and sleeping until the late afternoon?

Adolescents naturally have their sleep cycle shift, so they are sleepy later and sleep longer. But staying up all night is usually about texting with friends or playing video games. The problem is that their sleep schedule can flip. They will not be able to participate in online class or enjoy exercise in the sun, and they rarely get enough sleep during the daytime, making them more irritable, anxious, inattentive, and tired. This will only make managing their schoolwork harder and increase the chances of conflict at home. So it is important to preserve rules around sleep. You might extend bedtime by an hour or so, but preserve rules and bedtime routines. Sleep is essential to health, well-being, and resilience, and all are critical during times of uncertainty and change.

We think our 17-year-old is using marijuana, and it might be a problem.

When parents think their children may have a problem with drugs, the children almost certainly do, as parents are typically the last to know about the extent of their use. Sheltering in place together may make their drug use much more apparent, and offer an opportunity for parents to respond. Talk with them about it. Let them know what you have noticed. See if they can tell you honestly about their drug use. Kids who are only experimenting socially are unlikely to be using drugs at home under quarantine. If you are truly calm and curious, they are more likely to be honest, and it could be a relief for them to discuss it with you. Find out what they think it helps, and what – if anything – they are worried about. Then share your concerns about marijuana use and the developing brain, and the risk of addiction. If they think it is “medical” use, remind them that anxiety or mood symptoms get better with therapy, whereas drugs (including marijuana) and alcohol actually worsen those problems. It is also a time to establish home rules, explain them, and enforce them. They will have your support while stopping and may learn that they are actually sleeping and feeling better after a few weeks without marijuana.

Parents should not hesitate to reach out to pediatric providers for guidance on local resources for assessment and treatment for substance abuse and addiction. These are medical problems, and they can become serious if untreated.

My 12-year-old perfectionist is very stressed about getting her work done well now that she is home schooling. How do I help her relax?

Some children, especially our anxious perfectionists, may respond to the switch to home school with great effort and organization. These kids usually are not the ones parents worry about. But they are very prone to expanding anxiety without the regular support and feedback of teachers. The school environment naturally encourages their taking chances and normalizes the setbacks and failures that are an essential part of learning something new. At home, parents are inclined to let these kids work independently. But they benefit from regular check-ins that are not focused on work completion or scores. Instead, ask about what they are doing that is hardest, and let them teach you about it. Model how you approach a new challenge, and how you regroup and try again when you don’t get it right. Finally, this is a good age to start discussing “reasonable expectations.” No one can “do their best” all the time; not parents, not professional athletes, not even machines can sustain long bursts of maximum speed without problems. Help them to start experimenting with different speeds and levels of effort, and see how it feels.

My 10-year-old is very anxious about catching coronavirus or one of us catching it. How do I help ease her anxiety when there is no certainty about how to prevent it?

Anxiety is a normal response to a situation with as much uncertainty as this one. But some are prone to more profound anxiety, and parents may find they are doing a lot of reassuring throughout the day. For especially anxious children (and adults), accommodating the anxiety by avoiding the stressful situation is a common response that provides temporary relief. But accommodation and avoidance actually fuel anxiety, and make it harder and harder to manage. It is important to talk about the “accommodations” we all are doing, how masks are recommended to protect others (not ourselves) and to slow down the spread of a new illness so our hospitals aren’t overwhelmed. It can seem counterintuitive, but rather than jumping to reassurance or dismissing their sense of risk, ask your children to play the full movie of what they are most worried about. What happens if they get sick? If you get sick? If they are worried about dying, go ahead and ask what they think happens then. You are demonstrating that you have confidence they can handle these feelings, and you are modeling curiosity – not avoidance – yourself. Correct any misunderstandings, check on facts together, acknowledge uncertainty. It also is very important for parents to assess whether their own anxiety level makes this task especially hard or may even be contributing to their children’s level of worry. Each of us is managing anxiety right now, and this moment presents an opportunity for all of us to learn about how we can face and bear it, learn to manage, and even master it.

We are all getting cabin fever at home and snapping at each other constantly. How do we keep the peace without just hiding in our rooms all day?

Cabin fever seems inevitable when a family is suddenly at home together all day every day with no end in sight. But if we establish some simple and realistic routines and preserve some structure without being rigid, it can go a long way to helping each member of a family to find their equilibrium in this new normal. Structure can be about preserving normal sleep and meal times. Ensuring everyone is getting adequate, restful sleep and is not hungry is probably the most powerful way to keep irritability and conflict low. It is also helpful to establish some new routines. These should be simple enough to be memorable and should be realistic. You might identify predictable blocks of time that are dedicated to school (or work), exercise, creative time, and family time. While much of the day may find each family member doing some independent activity, it helps when these “blocks” are the same for everybody. Try to consistently do one or two things together, like a walk after the family dinner or family game time. And also remember that everyone needs some alone time. Respect their need for this, and it will help you to explain when you need it. If someone wants to sit out the family Yahtzee tournament, don’t shame or punish them. Just invite them again the next night!

What are going to be the consequences of all this screen time?

The great majority of kids (and parents) will not suffer any adverse consequences from the increased amount of time spent in front of screens when these activities are varied and serve a useful purpose – including distraction, senseless fun, and social time. Beyond letter or email writing, screen and phone time are the only ways to stay socially connected while physically distant. But parents are the experts on their kids. Youth who are depressed and have in the past wanted to escape into long hours of video games or YouTube videos should not be allowed to do that now. Youth with attentional issues who have a hard time stopping video games will still have that difficulty. If they are getting adequate sleep and regular exercise, and are doing most of their school work and staying socially connected, screens are not dangerous. They are proving to be a wonderful tool to help us visit libraries and museums, take dance classes, learn new languages, follow the news, order groceries, or enjoy a movie together. If we stay connected to those we care about and to the world, then this time – although marked by profound suffering and loss – may prove to be a time when we were able to slow down and remember what truly matters in our lives.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

We are living through unprecedented challenges, faced with profound uncertainties about the public health, the economy, the safety of our workplaces, the risks of gathering with friends and family, and even about the rhythm of the school year. Parents always have sought guidance from their pediatric providers when they are uncertain about their children’s health, behavior, and development. We want to share some guidance with you about several of the most common questions we have been hearing in the past few months, in the hope that it may prove useful in your conversations with patients and families.

ArtMarie/E+

What happens when we are so busy at home that our 2-year-old is ignored for much of the day?

If they are fortunate enough to be able to work from home, but have lost their child care, many parents are suddenly facing the sustained challenge of parenting while working. Even older children will have a tough time remembering that home is now a workplace, and they can’t interrupt their parents during a Zoom meeting. But older children will understand. Younger children (preschoolers) simply will not be able to understand that their parents are in sight but not fully available to them. They are exquisitely sensitive to their parents’ attention. If they are consistently ignored, behavioral problems can emerge. If both parents are at home, they should try to arrange a schedule taking turns so that one of them could turn their full attention to their kids if need be. If a working parent can be out of sight (i.e., in another room), it makes the situation easier for everyone.

If there is only one parent at home, that mom or dad should consider arranging a babysitter or sharing child care with a friend, with some reasonable safety provisions in place. The small risk of exposure to the virus is balanced by the risk of sustained invalidation in a developing child. Help parents set reasonable expectations for how productive they can be at home. If possible, they can manage their employer’s expectations, so that they do not find themselves in the impossible bind of choosing between a crying child and a crucial deadline. If they can work near the child (and be prepared for interruptions) when reading emails or writing, that may be enough availability for the child. And parents should not be discouraged when they have to repeatedly remind their children that they adore them, but also have to work while they are at home right now. Using age-appropriate screen time as a babysitter for a few hours each day is a perfectly acceptable part of a plan. Simply planning regular breaks when their children can have their attention will make the day easier for everyone at home.
 

What can I do about my 13-year-old who is lying around the house all day?

This is a time to pick your battles. If children can keep their regular sleep schedule, get their schoolwork done, and do some physical exercise every day, they are doing great. And if parents are continuously complaining that they are being lazy, it will probably cease to mean much to them. Instead, focus on clear, simple expectations, and parents should live by them, too. If parents can exercise with them, or try a new activity, that is a wonderful way to model self-care and trying new things. It is important to remember that the developmental task for a 13-year-old is to establish new avenues of independence that they will drive down further with each passing year. Give them some leeway to experiment and figure out their own way of handling this challenge, although it is bound to create some tension. Parents should always acknowledge how hard it is to stick with schoolwork without school, exercise without a team, practice music without a band, or do your work without an office!

What do we do about our 16-year-old who is staying up all night and sleeping until the late afternoon?

Adolescents naturally have their sleep cycle shift, so they are sleepy later and sleep longer. But staying up all night is usually about texting with friends or playing video games. The problem is that their sleep schedule can flip. They will not be able to participate in online class or enjoy exercise in the sun, and they rarely get enough sleep during the daytime, making them more irritable, anxious, inattentive, and tired. This will only make managing their schoolwork harder and increase the chances of conflict at home. So it is important to preserve rules around sleep. You might extend bedtime by an hour or so, but preserve rules and bedtime routines. Sleep is essential to health, well-being, and resilience, and all are critical during times of uncertainty and change.

We think our 17-year-old is using marijuana, and it might be a problem.

When parents think their children may have a problem with drugs, the children almost certainly do, as parents are typically the last to know about the extent of their use. Sheltering in place together may make their drug use much more apparent, and offer an opportunity for parents to respond. Talk with them about it. Let them know what you have noticed. See if they can tell you honestly about their drug use. Kids who are only experimenting socially are unlikely to be using drugs at home under quarantine. If you are truly calm and curious, they are more likely to be honest, and it could be a relief for them to discuss it with you. Find out what they think it helps, and what – if anything – they are worried about. Then share your concerns about marijuana use and the developing brain, and the risk of addiction. If they think it is “medical” use, remind them that anxiety or mood symptoms get better with therapy, whereas drugs (including marijuana) and alcohol actually worsen those problems. It is also a time to establish home rules, explain them, and enforce them. They will have your support while stopping and may learn that they are actually sleeping and feeling better after a few weeks without marijuana.

Parents should not hesitate to reach out to pediatric providers for guidance on local resources for assessment and treatment for substance abuse and addiction. These are medical problems, and they can become serious if untreated.

My 12-year-old perfectionist is very stressed about getting her work done well now that she is home schooling. How do I help her relax?

Some children, especially our anxious perfectionists, may respond to the switch to home school with great effort and organization. These kids usually are not the ones parents worry about. But they are very prone to expanding anxiety without the regular support and feedback of teachers. The school environment naturally encourages their taking chances and normalizes the setbacks and failures that are an essential part of learning something new. At home, parents are inclined to let these kids work independently. But they benefit from regular check-ins that are not focused on work completion or scores. Instead, ask about what they are doing that is hardest, and let them teach you about it. Model how you approach a new challenge, and how you regroup and try again when you don’t get it right. Finally, this is a good age to start discussing “reasonable expectations.” No one can “do their best” all the time; not parents, not professional athletes, not even machines can sustain long bursts of maximum speed without problems. Help them to start experimenting with different speeds and levels of effort, and see how it feels.

My 10-year-old is very anxious about catching coronavirus or one of us catching it. How do I help ease her anxiety when there is no certainty about how to prevent it?

Anxiety is a normal response to a situation with as much uncertainty as this one. But some are prone to more profound anxiety, and parents may find they are doing a lot of reassuring throughout the day. For especially anxious children (and adults), accommodating the anxiety by avoiding the stressful situation is a common response that provides temporary relief. But accommodation and avoidance actually fuel anxiety, and make it harder and harder to manage. It is important to talk about the “accommodations” we all are doing, how masks are recommended to protect others (not ourselves) and to slow down the spread of a new illness so our hospitals aren’t overwhelmed. It can seem counterintuitive, but rather than jumping to reassurance or dismissing their sense of risk, ask your children to play the full movie of what they are most worried about. What happens if they get sick? If you get sick? If they are worried about dying, go ahead and ask what they think happens then. You are demonstrating that you have confidence they can handle these feelings, and you are modeling curiosity – not avoidance – yourself. Correct any misunderstandings, check on facts together, acknowledge uncertainty. It also is very important for parents to assess whether their own anxiety level makes this task especially hard or may even be contributing to their children’s level of worry. Each of us is managing anxiety right now, and this moment presents an opportunity for all of us to learn about how we can face and bear it, learn to manage, and even master it.

We are all getting cabin fever at home and snapping at each other constantly. How do we keep the peace without just hiding in our rooms all day?

Cabin fever seems inevitable when a family is suddenly at home together all day every day with no end in sight. But if we establish some simple and realistic routines and preserve some structure without being rigid, it can go a long way to helping each member of a family to find their equilibrium in this new normal. Structure can be about preserving normal sleep and meal times. Ensuring everyone is getting adequate, restful sleep and is not hungry is probably the most powerful way to keep irritability and conflict low. It is also helpful to establish some new routines. These should be simple enough to be memorable and should be realistic. You might identify predictable blocks of time that are dedicated to school (or work), exercise, creative time, and family time. While much of the day may find each family member doing some independent activity, it helps when these “blocks” are the same for everybody. Try to consistently do one or two things together, like a walk after the family dinner or family game time. And also remember that everyone needs some alone time. Respect their need for this, and it will help you to explain when you need it. If someone wants to sit out the family Yahtzee tournament, don’t shame or punish them. Just invite them again the next night!

What are going to be the consequences of all this screen time?

The great majority of kids (and parents) will not suffer any adverse consequences from the increased amount of time spent in front of screens when these activities are varied and serve a useful purpose – including distraction, senseless fun, and social time. Beyond letter or email writing, screen and phone time are the only ways to stay socially connected while physically distant. But parents are the experts on their kids. Youth who are depressed and have in the past wanted to escape into long hours of video games or YouTube videos should not be allowed to do that now. Youth with attentional issues who have a hard time stopping video games will still have that difficulty. If they are getting adequate sleep and regular exercise, and are doing most of their school work and staying socially connected, screens are not dangerous. They are proving to be a wonderful tool to help us visit libraries and museums, take dance classes, learn new languages, follow the news, order groceries, or enjoy a movie together. If we stay connected to those we care about and to the world, then this time – although marked by profound suffering and loss – may prove to be a time when we were able to slow down and remember what truly matters in our lives.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at pdnews@mdedge.com.

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.