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The Cures Act: Is the “cure” worse than the disease?
There is a sudden spill of icy anxiety down your spine as you pick up your phone in your shaking hands. It’s 6 p.m.; your doctor’s office is closed. You open the message, and your worst fears are confirmed ... the cancer is back.
Or is it? You’re not sure. The biopsy sure sounds bad. But you’re an English teacher, not a doctor, and you spend the rest of the night Googling words like “tubulovillous” and “high-grade dysplasia.” You sit awake, terrified in front of the computer screen desperately trying to make sense of the possibly life-changing results. You wish you knew someone who could help you understand; you consider calling your doctor’s emergency line, or your cousin who is an ophthalmologist – anybody who can help you make sense of the results.
Or imagine another scenario: you’re a trans teen who has asked your doctor to refer to you by your preferred pronouns. You’re still presenting as your birth sex, in part because your family would disown you if they knew, and you’re not financially or emotionally ready for that step. You feel proud of yourself for advocating for your needs to your long-time physician, and excited about the resources they’ve included in your after visit summary and the referrals they’d made to gender-confirming specialists.
When you get home, you are confronted with a terrible reality that your doctor’s notes, orders, and recommendations are immediately viewable to anybody with your MyChart login – your parents knew the second your doctor signed the note. They received the notification, logged on as your guardians, and you have effectively been “outed” by the physician who took and oath to care for you and who you trusted implicitly.
How the Cures Act is affecting patients
While these examples may sound extreme, they are becoming more and more commonplace thanks to a recently enacted 21st Century Cures Act. The act was originally written to improve communication between physicians and patients. Part of the act stipulates that nearly all medical information – from notes to biopsies to lab results – must be available within 24 hours, published to a patient portal and a notification be sent to the patient by phone.
Oftentimes, this occurs before the ordering physician has even seen the results, much less interpreted them and made a plan for the patient. What happens now, not long after its enactment date, when it has become clear that the Cures Act is causing extreme harm to our patients?
Take, for example, the real example of a physician whose patient found out about her own intrauterine fetal demise by way of an EMR text message alert of “new imaging results!” sent directly to her phone. Or a physician colleague who witnessed firsthand the intrusive unhelpfulness of the Cures Act when she was informed via patient portal releasing her imaging information that she had a large, possibly malignant breast mass. “No phone call,” she said. “No human being for questions or comfort. Just a notification on my phone.”
The stories about the impact of the Cures Act across the medical community are an endless stream of anxiety, hurt, and broken trust. The relationship between a physician and a patient should be sacred, bolstered by communication and mutual respect.
In many ways, the new act feels like a third party to the patient-physician relationship – a digital imposter, oftentimes blurting out personal and life-altering medical information without any of the finesse, context, and perspective of an experienced physician.
Breaking ‘bad news’ to a patient
In training, some residents are taught how to “break bad news” to a patient. Some good practices for doing this are to have information available for the patient, provide emotional support, have a plan for their next steps already formulated, and call the appropriate specialist ahead of time if you can.
Above all, it’s most important to let the patient be the one to direct their own care. Give them time to ask questions and answer them honestly and clearly. Ask them how much they want to know and help them to understand the complex change in their usual state of health.
Now, unless physicians are keeping a very close eye on their inbox, results are slipping out to patients in a void. The bad news conversations aren’t happening at all, or if they are, they’re happening at 8 p.m. on a phone call after an exhausted physician ends their shift but has to slog through their results bin, calling all the patients who shouldn’t have to find out their results in solitude.
Reaching out to these patients immediately is an honorable, kind thing to, but for a physician, knowing they need to beat the patient to opening an email creates anxiety. Plus, making these calls at whatever hour the results are released to a patient is another burden added to doctors’ already-full plates.
Interpreting results
None of us want to harm our patients. All of us want to be there for them. But this act stands in the way of delivering quality, humanizing medical care.
It is true that patients have a right to access their own medical information. It is also true that waiting anxiously on results can cause undue harm to a patient. But the across-the-board, breakneck speed of information release mandated in this act causes irreparable harm not only to patients, but to the patient-physician relationship.
No patient should find out their cancer recurred while checking their emails at their desk. No patient should first learn of a life-altering diagnosis by way of scrolling through their smartphone in bed. The role of a physician is more than just a healer – we should also be educators, interpreters, partners and, first and foremost, advocates for our patients’ needs.
Our patients are depending on us to stand up and speak out about necessary changes to this act. Result releases should be delayed until they are viewed by a physician. Our patients deserve the dignity and opportunity of a conversation with their medical provider about their test results, and physicians deserve the chance to interpret results and frame the conversation in a way which is conducive to patient understanding and healing.
Dr. Persampiere is a first-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece. You can contact them at fpnews@mdedge.com.
There is a sudden spill of icy anxiety down your spine as you pick up your phone in your shaking hands. It’s 6 p.m.; your doctor’s office is closed. You open the message, and your worst fears are confirmed ... the cancer is back.
Or is it? You’re not sure. The biopsy sure sounds bad. But you’re an English teacher, not a doctor, and you spend the rest of the night Googling words like “tubulovillous” and “high-grade dysplasia.” You sit awake, terrified in front of the computer screen desperately trying to make sense of the possibly life-changing results. You wish you knew someone who could help you understand; you consider calling your doctor’s emergency line, or your cousin who is an ophthalmologist – anybody who can help you make sense of the results.
Or imagine another scenario: you’re a trans teen who has asked your doctor to refer to you by your preferred pronouns. You’re still presenting as your birth sex, in part because your family would disown you if they knew, and you’re not financially or emotionally ready for that step. You feel proud of yourself for advocating for your needs to your long-time physician, and excited about the resources they’ve included in your after visit summary and the referrals they’d made to gender-confirming specialists.
When you get home, you are confronted with a terrible reality that your doctor’s notes, orders, and recommendations are immediately viewable to anybody with your MyChart login – your parents knew the second your doctor signed the note. They received the notification, logged on as your guardians, and you have effectively been “outed” by the physician who took and oath to care for you and who you trusted implicitly.
How the Cures Act is affecting patients
While these examples may sound extreme, they are becoming more and more commonplace thanks to a recently enacted 21st Century Cures Act. The act was originally written to improve communication between physicians and patients. Part of the act stipulates that nearly all medical information – from notes to biopsies to lab results – must be available within 24 hours, published to a patient portal and a notification be sent to the patient by phone.
Oftentimes, this occurs before the ordering physician has even seen the results, much less interpreted them and made a plan for the patient. What happens now, not long after its enactment date, when it has become clear that the Cures Act is causing extreme harm to our patients?
Take, for example, the real example of a physician whose patient found out about her own intrauterine fetal demise by way of an EMR text message alert of “new imaging results!” sent directly to her phone. Or a physician colleague who witnessed firsthand the intrusive unhelpfulness of the Cures Act when she was informed via patient portal releasing her imaging information that she had a large, possibly malignant breast mass. “No phone call,” she said. “No human being for questions or comfort. Just a notification on my phone.”
The stories about the impact of the Cures Act across the medical community are an endless stream of anxiety, hurt, and broken trust. The relationship between a physician and a patient should be sacred, bolstered by communication and mutual respect.
In many ways, the new act feels like a third party to the patient-physician relationship – a digital imposter, oftentimes blurting out personal and life-altering medical information without any of the finesse, context, and perspective of an experienced physician.
Breaking ‘bad news’ to a patient
In training, some residents are taught how to “break bad news” to a patient. Some good practices for doing this are to have information available for the patient, provide emotional support, have a plan for their next steps already formulated, and call the appropriate specialist ahead of time if you can.
Above all, it’s most important to let the patient be the one to direct their own care. Give them time to ask questions and answer them honestly and clearly. Ask them how much they want to know and help them to understand the complex change in their usual state of health.
Now, unless physicians are keeping a very close eye on their inbox, results are slipping out to patients in a void. The bad news conversations aren’t happening at all, or if they are, they’re happening at 8 p.m. on a phone call after an exhausted physician ends their shift but has to slog through their results bin, calling all the patients who shouldn’t have to find out their results in solitude.
Reaching out to these patients immediately is an honorable, kind thing to, but for a physician, knowing they need to beat the patient to opening an email creates anxiety. Plus, making these calls at whatever hour the results are released to a patient is another burden added to doctors’ already-full plates.
Interpreting results
None of us want to harm our patients. All of us want to be there for them. But this act stands in the way of delivering quality, humanizing medical care.
It is true that patients have a right to access their own medical information. It is also true that waiting anxiously on results can cause undue harm to a patient. But the across-the-board, breakneck speed of information release mandated in this act causes irreparable harm not only to patients, but to the patient-physician relationship.
No patient should find out their cancer recurred while checking their emails at their desk. No patient should first learn of a life-altering diagnosis by way of scrolling through their smartphone in bed. The role of a physician is more than just a healer – we should also be educators, interpreters, partners and, first and foremost, advocates for our patients’ needs.
Our patients are depending on us to stand up and speak out about necessary changes to this act. Result releases should be delayed until they are viewed by a physician. Our patients deserve the dignity and opportunity of a conversation with their medical provider about their test results, and physicians deserve the chance to interpret results and frame the conversation in a way which is conducive to patient understanding and healing.
Dr. Persampiere is a first-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece. You can contact them at fpnews@mdedge.com.
There is a sudden spill of icy anxiety down your spine as you pick up your phone in your shaking hands. It’s 6 p.m.; your doctor’s office is closed. You open the message, and your worst fears are confirmed ... the cancer is back.
Or is it? You’re not sure. The biopsy sure sounds bad. But you’re an English teacher, not a doctor, and you spend the rest of the night Googling words like “tubulovillous” and “high-grade dysplasia.” You sit awake, terrified in front of the computer screen desperately trying to make sense of the possibly life-changing results. You wish you knew someone who could help you understand; you consider calling your doctor’s emergency line, or your cousin who is an ophthalmologist – anybody who can help you make sense of the results.
Or imagine another scenario: you’re a trans teen who has asked your doctor to refer to you by your preferred pronouns. You’re still presenting as your birth sex, in part because your family would disown you if they knew, and you’re not financially or emotionally ready for that step. You feel proud of yourself for advocating for your needs to your long-time physician, and excited about the resources they’ve included in your after visit summary and the referrals they’d made to gender-confirming specialists.
When you get home, you are confronted with a terrible reality that your doctor’s notes, orders, and recommendations are immediately viewable to anybody with your MyChart login – your parents knew the second your doctor signed the note. They received the notification, logged on as your guardians, and you have effectively been “outed” by the physician who took and oath to care for you and who you trusted implicitly.
How the Cures Act is affecting patients
While these examples may sound extreme, they are becoming more and more commonplace thanks to a recently enacted 21st Century Cures Act. The act was originally written to improve communication between physicians and patients. Part of the act stipulates that nearly all medical information – from notes to biopsies to lab results – must be available within 24 hours, published to a patient portal and a notification be sent to the patient by phone.
Oftentimes, this occurs before the ordering physician has even seen the results, much less interpreted them and made a plan for the patient. What happens now, not long after its enactment date, when it has become clear that the Cures Act is causing extreme harm to our patients?
Take, for example, the real example of a physician whose patient found out about her own intrauterine fetal demise by way of an EMR text message alert of “new imaging results!” sent directly to her phone. Or a physician colleague who witnessed firsthand the intrusive unhelpfulness of the Cures Act when she was informed via patient portal releasing her imaging information that she had a large, possibly malignant breast mass. “No phone call,” she said. “No human being for questions or comfort. Just a notification on my phone.”
The stories about the impact of the Cures Act across the medical community are an endless stream of anxiety, hurt, and broken trust. The relationship between a physician and a patient should be sacred, bolstered by communication and mutual respect.
In many ways, the new act feels like a third party to the patient-physician relationship – a digital imposter, oftentimes blurting out personal and life-altering medical information without any of the finesse, context, and perspective of an experienced physician.
Breaking ‘bad news’ to a patient
In training, some residents are taught how to “break bad news” to a patient. Some good practices for doing this are to have information available for the patient, provide emotional support, have a plan for their next steps already formulated, and call the appropriate specialist ahead of time if you can.
Above all, it’s most important to let the patient be the one to direct their own care. Give them time to ask questions and answer them honestly and clearly. Ask them how much they want to know and help them to understand the complex change in their usual state of health.
Now, unless physicians are keeping a very close eye on their inbox, results are slipping out to patients in a void. The bad news conversations aren’t happening at all, or if they are, they’re happening at 8 p.m. on a phone call after an exhausted physician ends their shift but has to slog through their results bin, calling all the patients who shouldn’t have to find out their results in solitude.
Reaching out to these patients immediately is an honorable, kind thing to, but for a physician, knowing they need to beat the patient to opening an email creates anxiety. Plus, making these calls at whatever hour the results are released to a patient is another burden added to doctors’ already-full plates.
Interpreting results
None of us want to harm our patients. All of us want to be there for them. But this act stands in the way of delivering quality, humanizing medical care.
It is true that patients have a right to access their own medical information. It is also true that waiting anxiously on results can cause undue harm to a patient. But the across-the-board, breakneck speed of information release mandated in this act causes irreparable harm not only to patients, but to the patient-physician relationship.
No patient should find out their cancer recurred while checking their emails at their desk. No patient should first learn of a life-altering diagnosis by way of scrolling through their smartphone in bed. The role of a physician is more than just a healer – we should also be educators, interpreters, partners and, first and foremost, advocates for our patients’ needs.
Our patients are depending on us to stand up and speak out about necessary changes to this act. Result releases should be delayed until they are viewed by a physician. Our patients deserve the dignity and opportunity of a conversation with their medical provider about their test results, and physicians deserve the chance to interpret results and frame the conversation in a way which is conducive to patient understanding and healing.
Dr. Persampiere is a first-year resident in the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece. You can contact them at fpnews@mdedge.com.
Cellular senescence, skin aging, and cosmeceuticals
I just completed the third edition of my Cosmetic Dermatology textbook (McGraw Hill), which will come out later this year. Although writing it is a huge effort, I really enjoy all the basic science. While I was working on the book, I was most surprised by the .
Right now, it is too early, and we don’t know enough yet, to have cosmeceuticals that affect cellular senescence and autophagy. But, it’s not too early to learn about this research, to avoid falling prey to any pseudoscience that invariably ends up affecting cosmeceuticals on the market. The following is a brief primer on cellular senescence, skin aging, and cosmeceuticals; it represents what we currently know.
Cell phases
Keratinocytes and fibroblasts go through five different phases: stem, proliferation, differentiation, senescence, and apoptosis. The difference between apoptotic cells and senescent cells is that apoptotic cells are not viable and are eliminated, while senescent cells, even though they have gone into cell cycle arrest, remain functional and are not eliminated from the skin.
What are senescent cells?
Senescent cells have lost the ability to proliferate but have not undergone apoptosis. Senescent human skin fibroblasts in cell culture lose the youthful spindlelike shape and become enlarged and flattened.1 Their lysosomes and mitochondria lose functionality.2 The presence of senescent cells is associated with increased aging and seems to speed aging.
Senescent cells and skin aging
Senescent cells are increased in the age-related phenotype3 because of an age-related decline of senescent cell removal systems, such as the immune system4 and the autophagy-lysosomal pathway.5 Senescent cells are deleterious because they develop into a senescence-associated secretory phenotype (SASP), which is believed to be one of the major causes of aging. SASP cells communicate with nearby cells using proinflammatory cytokines, which include catabolic modulators such as Matrix metalloproteinases. They are known to release growth factors, cytokines, chemokines, matrix-modeling enzymes, lipids, and extracellular vesicles. The last are lipid bilayer-lined vesicles that can transport functional RNA and microRNA and facilitate other modes of communication between cells.6
The SASP is likely a natural tumor suppressive mode employed by cells to prevent cells with cancerous mutations from undergoing replication;7 however, when it comes to aging, the deleterious effects of SASP outweigh the beneficial effects. For example, SASP contributes to a prolonged state of inflammation, known as “inflammaging,”8 which is detrimental to the skin’s appearance. Human fibroblasts that have assumed the SASP secrete proinflammatory cytokines and MMPs and release reactive oxygen species,9,10 resulting in degradation of the surrounding extracellular matrix (ECM). Loss of the ECM leads to fibroblast compaction and reduced DNA synthesis, all caused by SASPs.9
What causes cellular senescence?
Activation of the nuclear factor-erythroid 2-related transcription factor 2 (NRF2) induces cellular senescence via direct targeting of certain ECM genes. NRF2 is a key regulator of the skin’s antioxidant defense system, which controls the transcription of genes encoding reactive oxygen species–detoxifying enzymes and various other antioxidant proteins.11 Loss of mitochondrial autophagy also induces senescence, as do activation of the TP53 gene, inactivity of SIRT-1, and short telomeres.
Cellular senescence and skin aging
Timely clearance of senescent cells before they create too much damage postpones the onset and severity of age-related diseases and extends the life span of mice.12,6 Antiaging treatments should focus on decreasing the number of senescent cells and reverting senescent cells to the more juvenile forms: proliferating or differentiating cells as an approach to prevent skin aging.13 Restoration of the lysosomal-mitochondrial axis has been shown to revert SASP back to a juvenile status. Normalization of the lysosomal-mitochondrial axis is a prerequisite to reverse senescence.14
Cellular senescence, autophagy, the lysosomal-mitochondrial axis, and cosmeceuticals
Autophagy is the important process of organelles, like mitochondria,15 self-digesting their cytoplasmic material into lysosomes for degradation. Mitochondrial autophagy is very important in slowing the aging process because damaged mitochondria generate free radicals. As you can imagine, much research is focused on this area, but it is too early for any research to translate to efficacious cosmeceuticals.
Conclusion
To summarize, activation of sirtuin-1 (SIRT-1) has been shown to extend the lifespan of mammals, as does caloric restriction.16 This extension occurs because SIRT-1 decreases senescence and activates autophagy.
Although we do not yet know whether topical skincare products could affect senescence or autophagy, there are data to show that oral resveratrol16 and melatonin17 activate SIRT-1 and increase autophagy. I am closely watching this research and will let you know if there are any similar data on topical cosmeceuticals targeting senescence or autophagy. Stay tuned!
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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Papadopoulou A et al. Biogerontology. 2020 Dec;21(6):695-708.
2. López-Otin C et al. Cell. 2013 June 6;153, 1194–217.
3. Yoon J E et al. Theranostics. 2018 Sep 9;8(17):4620-32.
4. Rodier F, Campisi J. J Cell Biol. 2011 Feb 21;192(4):547-56.
5. Dutta D et al. Circ Res. 2012 Apr 13;110(8):1125-38.
6. Terlecki-Zaniewicz L et al. J Invest Dermatol. 2019 Dec;139(12):2425-36.e5.
7. Campisi J et al. Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40.
8. Franceschi C and Campisi J. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
9. Nelson G et al. Aging Cell. 2012 Apr;11(2):345-9.
10. Passos JF et al. PLoS Biol. 2007 May;5(5):e110.
11. Hiebert P et al. Dev Cell. 2018 Jul 16;46(2):145-61.e10.
12. Baker DJ et al. Nature. 2016 Feb 11:530(7589):184-9.
13. Mavrogonatou E et al. Matrix Biol. 2019 Jan;75-76:27-42.
14. Park JT et al. Ageing Res Rev. 2018 Nov;47:176-82.
15. Levine B and Kroemer G. Cell. 2019 Jan 10;176(1-2):11-42.
16. Morselli E et al. Cell Death Dis. 2010;1(1):e10.
17. Lee JH et al. Oncotarget. 2016 Mar 15;7(11):12075-88.
I just completed the third edition of my Cosmetic Dermatology textbook (McGraw Hill), which will come out later this year. Although writing it is a huge effort, I really enjoy all the basic science. While I was working on the book, I was most surprised by the .
Right now, it is too early, and we don’t know enough yet, to have cosmeceuticals that affect cellular senescence and autophagy. But, it’s not too early to learn about this research, to avoid falling prey to any pseudoscience that invariably ends up affecting cosmeceuticals on the market. The following is a brief primer on cellular senescence, skin aging, and cosmeceuticals; it represents what we currently know.
Cell phases
Keratinocytes and fibroblasts go through five different phases: stem, proliferation, differentiation, senescence, and apoptosis. The difference between apoptotic cells and senescent cells is that apoptotic cells are not viable and are eliminated, while senescent cells, even though they have gone into cell cycle arrest, remain functional and are not eliminated from the skin.
What are senescent cells?
Senescent cells have lost the ability to proliferate but have not undergone apoptosis. Senescent human skin fibroblasts in cell culture lose the youthful spindlelike shape and become enlarged and flattened.1 Their lysosomes and mitochondria lose functionality.2 The presence of senescent cells is associated with increased aging and seems to speed aging.
Senescent cells and skin aging
Senescent cells are increased in the age-related phenotype3 because of an age-related decline of senescent cell removal systems, such as the immune system4 and the autophagy-lysosomal pathway.5 Senescent cells are deleterious because they develop into a senescence-associated secretory phenotype (SASP), which is believed to be one of the major causes of aging. SASP cells communicate with nearby cells using proinflammatory cytokines, which include catabolic modulators such as Matrix metalloproteinases. They are known to release growth factors, cytokines, chemokines, matrix-modeling enzymes, lipids, and extracellular vesicles. The last are lipid bilayer-lined vesicles that can transport functional RNA and microRNA and facilitate other modes of communication between cells.6
The SASP is likely a natural tumor suppressive mode employed by cells to prevent cells with cancerous mutations from undergoing replication;7 however, when it comes to aging, the deleterious effects of SASP outweigh the beneficial effects. For example, SASP contributes to a prolonged state of inflammation, known as “inflammaging,”8 which is detrimental to the skin’s appearance. Human fibroblasts that have assumed the SASP secrete proinflammatory cytokines and MMPs and release reactive oxygen species,9,10 resulting in degradation of the surrounding extracellular matrix (ECM). Loss of the ECM leads to fibroblast compaction and reduced DNA synthesis, all caused by SASPs.9
What causes cellular senescence?
Activation of the nuclear factor-erythroid 2-related transcription factor 2 (NRF2) induces cellular senescence via direct targeting of certain ECM genes. NRF2 is a key regulator of the skin’s antioxidant defense system, which controls the transcription of genes encoding reactive oxygen species–detoxifying enzymes and various other antioxidant proteins.11 Loss of mitochondrial autophagy also induces senescence, as do activation of the TP53 gene, inactivity of SIRT-1, and short telomeres.
Cellular senescence and skin aging
Timely clearance of senescent cells before they create too much damage postpones the onset and severity of age-related diseases and extends the life span of mice.12,6 Antiaging treatments should focus on decreasing the number of senescent cells and reverting senescent cells to the more juvenile forms: proliferating or differentiating cells as an approach to prevent skin aging.13 Restoration of the lysosomal-mitochondrial axis has been shown to revert SASP back to a juvenile status. Normalization of the lysosomal-mitochondrial axis is a prerequisite to reverse senescence.14
Cellular senescence, autophagy, the lysosomal-mitochondrial axis, and cosmeceuticals
Autophagy is the important process of organelles, like mitochondria,15 self-digesting their cytoplasmic material into lysosomes for degradation. Mitochondrial autophagy is very important in slowing the aging process because damaged mitochondria generate free radicals. As you can imagine, much research is focused on this area, but it is too early for any research to translate to efficacious cosmeceuticals.
Conclusion
To summarize, activation of sirtuin-1 (SIRT-1) has been shown to extend the lifespan of mammals, as does caloric restriction.16 This extension occurs because SIRT-1 decreases senescence and activates autophagy.
Although we do not yet know whether topical skincare products could affect senescence or autophagy, there are data to show that oral resveratrol16 and melatonin17 activate SIRT-1 and increase autophagy. I am closely watching this research and will let you know if there are any similar data on topical cosmeceuticals targeting senescence or autophagy. Stay tuned!
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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Papadopoulou A et al. Biogerontology. 2020 Dec;21(6):695-708.
2. López-Otin C et al. Cell. 2013 June 6;153, 1194–217.
3. Yoon J E et al. Theranostics. 2018 Sep 9;8(17):4620-32.
4. Rodier F, Campisi J. J Cell Biol. 2011 Feb 21;192(4):547-56.
5. Dutta D et al. Circ Res. 2012 Apr 13;110(8):1125-38.
6. Terlecki-Zaniewicz L et al. J Invest Dermatol. 2019 Dec;139(12):2425-36.e5.
7. Campisi J et al. Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40.
8. Franceschi C and Campisi J. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
9. Nelson G et al. Aging Cell. 2012 Apr;11(2):345-9.
10. Passos JF et al. PLoS Biol. 2007 May;5(5):e110.
11. Hiebert P et al. Dev Cell. 2018 Jul 16;46(2):145-61.e10.
12. Baker DJ et al. Nature. 2016 Feb 11:530(7589):184-9.
13. Mavrogonatou E et al. Matrix Biol. 2019 Jan;75-76:27-42.
14. Park JT et al. Ageing Res Rev. 2018 Nov;47:176-82.
15. Levine B and Kroemer G. Cell. 2019 Jan 10;176(1-2):11-42.
16. Morselli E et al. Cell Death Dis. 2010;1(1):e10.
17. Lee JH et al. Oncotarget. 2016 Mar 15;7(11):12075-88.
I just completed the third edition of my Cosmetic Dermatology textbook (McGraw Hill), which will come out later this year. Although writing it is a huge effort, I really enjoy all the basic science. While I was working on the book, I was most surprised by the .
Right now, it is too early, and we don’t know enough yet, to have cosmeceuticals that affect cellular senescence and autophagy. But, it’s not too early to learn about this research, to avoid falling prey to any pseudoscience that invariably ends up affecting cosmeceuticals on the market. The following is a brief primer on cellular senescence, skin aging, and cosmeceuticals; it represents what we currently know.
Cell phases
Keratinocytes and fibroblasts go through five different phases: stem, proliferation, differentiation, senescence, and apoptosis. The difference between apoptotic cells and senescent cells is that apoptotic cells are not viable and are eliminated, while senescent cells, even though they have gone into cell cycle arrest, remain functional and are not eliminated from the skin.
What are senescent cells?
Senescent cells have lost the ability to proliferate but have not undergone apoptosis. Senescent human skin fibroblasts in cell culture lose the youthful spindlelike shape and become enlarged and flattened.1 Their lysosomes and mitochondria lose functionality.2 The presence of senescent cells is associated with increased aging and seems to speed aging.
Senescent cells and skin aging
Senescent cells are increased in the age-related phenotype3 because of an age-related decline of senescent cell removal systems, such as the immune system4 and the autophagy-lysosomal pathway.5 Senescent cells are deleterious because they develop into a senescence-associated secretory phenotype (SASP), which is believed to be one of the major causes of aging. SASP cells communicate with nearby cells using proinflammatory cytokines, which include catabolic modulators such as Matrix metalloproteinases. They are known to release growth factors, cytokines, chemokines, matrix-modeling enzymes, lipids, and extracellular vesicles. The last are lipid bilayer-lined vesicles that can transport functional RNA and microRNA and facilitate other modes of communication between cells.6
The SASP is likely a natural tumor suppressive mode employed by cells to prevent cells with cancerous mutations from undergoing replication;7 however, when it comes to aging, the deleterious effects of SASP outweigh the beneficial effects. For example, SASP contributes to a prolonged state of inflammation, known as “inflammaging,”8 which is detrimental to the skin’s appearance. Human fibroblasts that have assumed the SASP secrete proinflammatory cytokines and MMPs and release reactive oxygen species,9,10 resulting in degradation of the surrounding extracellular matrix (ECM). Loss of the ECM leads to fibroblast compaction and reduced DNA synthesis, all caused by SASPs.9
What causes cellular senescence?
Activation of the nuclear factor-erythroid 2-related transcription factor 2 (NRF2) induces cellular senescence via direct targeting of certain ECM genes. NRF2 is a key regulator of the skin’s antioxidant defense system, which controls the transcription of genes encoding reactive oxygen species–detoxifying enzymes and various other antioxidant proteins.11 Loss of mitochondrial autophagy also induces senescence, as do activation of the TP53 gene, inactivity of SIRT-1, and short telomeres.
Cellular senescence and skin aging
Timely clearance of senescent cells before they create too much damage postpones the onset and severity of age-related diseases and extends the life span of mice.12,6 Antiaging treatments should focus on decreasing the number of senescent cells and reverting senescent cells to the more juvenile forms: proliferating or differentiating cells as an approach to prevent skin aging.13 Restoration of the lysosomal-mitochondrial axis has been shown to revert SASP back to a juvenile status. Normalization of the lysosomal-mitochondrial axis is a prerequisite to reverse senescence.14
Cellular senescence, autophagy, the lysosomal-mitochondrial axis, and cosmeceuticals
Autophagy is the important process of organelles, like mitochondria,15 self-digesting their cytoplasmic material into lysosomes for degradation. Mitochondrial autophagy is very important in slowing the aging process because damaged mitochondria generate free radicals. As you can imagine, much research is focused on this area, but it is too early for any research to translate to efficacious cosmeceuticals.
Conclusion
To summarize, activation of sirtuin-1 (SIRT-1) has been shown to extend the lifespan of mammals, as does caloric restriction.16 This extension occurs because SIRT-1 decreases senescence and activates autophagy.
Although we do not yet know whether topical skincare products could affect senescence or autophagy, there are data to show that oral resveratrol16 and melatonin17 activate SIRT-1 and increase autophagy. I am closely watching this research and will let you know if there are any similar data on topical cosmeceuticals targeting senescence or autophagy. Stay tuned!
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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Papadopoulou A et al. Biogerontology. 2020 Dec;21(6):695-708.
2. López-Otin C et al. Cell. 2013 June 6;153, 1194–217.
3. Yoon J E et al. Theranostics. 2018 Sep 9;8(17):4620-32.
4. Rodier F, Campisi J. J Cell Biol. 2011 Feb 21;192(4):547-56.
5. Dutta D et al. Circ Res. 2012 Apr 13;110(8):1125-38.
6. Terlecki-Zaniewicz L et al. J Invest Dermatol. 2019 Dec;139(12):2425-36.e5.
7. Campisi J et al. Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40.
8. Franceschi C and Campisi J. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
9. Nelson G et al. Aging Cell. 2012 Apr;11(2):345-9.
10. Passos JF et al. PLoS Biol. 2007 May;5(5):e110.
11. Hiebert P et al. Dev Cell. 2018 Jul 16;46(2):145-61.e10.
12. Baker DJ et al. Nature. 2016 Feb 11:530(7589):184-9.
13. Mavrogonatou E et al. Matrix Biol. 2019 Jan;75-76:27-42.
14. Park JT et al. Ageing Res Rev. 2018 Nov;47:176-82.
15. Levine B and Kroemer G. Cell. 2019 Jan 10;176(1-2):11-42.
16. Morselli E et al. Cell Death Dis. 2010;1(1):e10.
17. Lee JH et al. Oncotarget. 2016 Mar 15;7(11):12075-88.
Screaming for screens: Digital well-being in the 2020s
Charlie is a 15-year-old male whose medical history includes overweight and autism spectrum disorder. While his autism symptoms are stable and he is doing fairly well in school, your sense is that he is underperforming and unhappy. His screening for anxiety and depression is not outstanding and you wonder whether to leave well enough alone.
Historically, pediatrician queries about media use happen in a minority of visits,1 overcrowded by the multitude of screening and acute care needs, let alone the pressures of electronic health record prompts, billing, and documentation. Yet the COVID-19 pandemic has emphasized what was already getting louder: screen life is becoming a ubiquitous, increasing, and normative function of child development. Digital well-being exhibits bidirectional interactions with most of the core indicators of child health: sleep, nutrition, safety, mood, relationships, and many other aspects of physical and mental health.1
The pandemic unveiled the blessings and curses of digital life by shifting many into remote work and school situations where screen time became both necessary and uncontrollable. Reeling with changes in employment, health, finances, and more, families struggled to forge a new screen-life balance that could bridge academic, professional, and recreational use.
Research has wavered in producing a verdict on the effects of screen time, in part because of limitations in methodology and follow-up time,2 and exacerbated by the quickly changing nature of screen use. Screen time may put youth at risk for obesity and behavior problems,3 but the latter may be mediated in part by loss of sleep because of late-night digital activity.4 While survey data at the population level show little link between screen time and well-being impairments,5 zooming in on individuals may tell a different story. Twenge and Campbell show light use of digital media (compared with nonuse) is associated with greater well-being while heavy use is associated with lower well-being and a higher risk for depression and suicidal behavior – especially in girls.6,7 Largely cross-sectional data show a small detriment to psychological well-being associated with digital technology, though this may be bidirectional and does not clearly differentiate types of technology.2
Recent neuroscience suggests that, compared with active play, sedentary screen time after school reduced impulse control and increased brain activity in regions associated with craving.8 This may explain some of the link between screen time and obesity. Brain imaging of preschoolers showed that greater screen time correlated with lower reading readiness as well as less integrity of white-matter tracts involved in language and executive function,9 whereas nurturing home reading practices were protective for language development and white matter integrity.10
Returning to the care of Charlie, providers may benefit from taking time to reflect on their own digital environment. What does the patient-side view of your office look like? Many offices use telephone reminders and patient portals, fill prescriptions electronically, and have waiting rooms with WiFi or devices for children’s use. Office visits share space with providers’ desktops, laptops, and smartphones, with EMRs guiding the visit. EMRs may come home for evening documentation. How does this affect provider digital well-being? How do you start the conversation with families about digital well-being?
The American Academy of Pediatrics recommends media screening be incorporated into routine pediatric care, with several tools available to support this. Adapting the HEADSSS model for psychosocial check-ins, Clark and colleagues propose an additional “S” to capture screen time.11 Their model queries which apps and social media are used, quantity of use, effects on self-confidence, and whether cyberbullying or sexting are occurring. Smartphones themselves provide an eye-opening and accessible dataset, with built-in features (for example, Screen Time for iOS) tracking not just daily duration of use, but also how frequently the phone is picked up and which apps get more use. Screening may be followed by motivational coaching, emphasizing nonjudgment, curiosity, empathy, and flexibility — for patient and provider.12
In Charlie’s case, screening reveals heavy use of social Internet games that connect him with like-minded peers. While he describes an inclusiveness and level of socialization that he has not found outside the home, the quantity of use is interfering with sleep, schoolwork, and physical activity.
Significant problematic Internet use may lead to intervention or referral – addictive behaviors and mental health symptoms may warrant connection with mental health providers. Cyberbullying or unsafe behaviors may additionally benefit from parental and school-based support. There is early and limited evidence that psychological and educational interventions may be of benefit for problematic Internet use.13
When digital life is not so dramatically affecting well-being, providers may begin by working with families on a media use plan. The AAP offers its own website to support this. Other well-researched and well-designed sites include Digital Wellness Lab For Parents, with developmentally staged information and plentiful research, and Common Sense Media, which reviews apps, movies, and more; plus they have a knowledge/advice section under “Parents Need to Know.” Keep in mind that digital media can also support youth in managing psychiatric problems, e.g., a digital intervention promoting positive psychology practices looked very helpful for young people with psychosis.14
For Charlie, a health coaching approach is adopted. Using Gabrielli’s TECH parenting rubric,15 Charlie’s parents are coached to make space to talk about and coview media and apps, as well as creating a Family Media Use Plan for everyone – parents included. Alongside setting limits on screen time; health promotion activities like exercise, reading, and schoolwork are also rewarded with extra screen time. When Charlie returns 3 months later, the family reports that, in recognition of their collective digital overload, they preserved dinnertime and after 10 p.m. as screen-free downtime. While they still have concerns about Charlie’s gaming and social life, his sleep is somewhat improved and family tension is lower.
Attention to digital well-being stands to benefit provider and patient alike, and over time may gain from the scaffolding of handouts, standardized assessments, and health coaching providers that may be in place to support other important domains like sleep hygiene, food security, and parenting.
Dr. Rosenfeld is assistant professor, University of Vermont, Vermont Center for Children, Youth, and Families, Burlington. He has no relevant disclosures.
References
1. Chassiakos YR et al. Pediatrics. 2016;138(5)e20162593.
2. Orben A. Soc Psychiatry Psych Epi. 2020;55(4):407.
3. Fang K et al. Child Care Health Dev. 2019;45(5):744-53.
4. Janssen X et al. Sleep Med Rev. 2020;49:101226.
5. George MJ et al. J Ped. 2020;219:180.
6. Twenge JM and Campbell WK. Psychiatry Q. 2019;90(2):311-31.
7. Twenge JM and Martin GN. J Adolesc. 2020;79:91.
8. Efraim M et al. Brain Imaging Behav. 2021;15(1):177-89.
9. Hutton JS et al. JAMA Pediatr. 2020;174(1):e193869.
10. Hutton JS et al. Acta Paediatr. 2020;109(7):1376-86.
11. Clark DL et al. Pediatrics. 2018;141(6).
12. Jericho M and Elliot A. Clin Child Psychol Psychiatry. 2020;25(3):662.
13. Malinauskas R and Malinauskine V. J Behav Addict. 2019;8(4):613.
14. Lim MH et al. Soc Psychiatry Psychiatr Epi. 2020;55(7):877-89.
15. Gabrielli J et al. Pediatrics. 2018;142(1)e20173718.
Charlie is a 15-year-old male whose medical history includes overweight and autism spectrum disorder. While his autism symptoms are stable and he is doing fairly well in school, your sense is that he is underperforming and unhappy. His screening for anxiety and depression is not outstanding and you wonder whether to leave well enough alone.
Historically, pediatrician queries about media use happen in a minority of visits,1 overcrowded by the multitude of screening and acute care needs, let alone the pressures of electronic health record prompts, billing, and documentation. Yet the COVID-19 pandemic has emphasized what was already getting louder: screen life is becoming a ubiquitous, increasing, and normative function of child development. Digital well-being exhibits bidirectional interactions with most of the core indicators of child health: sleep, nutrition, safety, mood, relationships, and many other aspects of physical and mental health.1
The pandemic unveiled the blessings and curses of digital life by shifting many into remote work and school situations where screen time became both necessary and uncontrollable. Reeling with changes in employment, health, finances, and more, families struggled to forge a new screen-life balance that could bridge academic, professional, and recreational use.
Research has wavered in producing a verdict on the effects of screen time, in part because of limitations in methodology and follow-up time,2 and exacerbated by the quickly changing nature of screen use. Screen time may put youth at risk for obesity and behavior problems,3 but the latter may be mediated in part by loss of sleep because of late-night digital activity.4 While survey data at the population level show little link between screen time and well-being impairments,5 zooming in on individuals may tell a different story. Twenge and Campbell show light use of digital media (compared with nonuse) is associated with greater well-being while heavy use is associated with lower well-being and a higher risk for depression and suicidal behavior – especially in girls.6,7 Largely cross-sectional data show a small detriment to psychological well-being associated with digital technology, though this may be bidirectional and does not clearly differentiate types of technology.2
Recent neuroscience suggests that, compared with active play, sedentary screen time after school reduced impulse control and increased brain activity in regions associated with craving.8 This may explain some of the link between screen time and obesity. Brain imaging of preschoolers showed that greater screen time correlated with lower reading readiness as well as less integrity of white-matter tracts involved in language and executive function,9 whereas nurturing home reading practices were protective for language development and white matter integrity.10
Returning to the care of Charlie, providers may benefit from taking time to reflect on their own digital environment. What does the patient-side view of your office look like? Many offices use telephone reminders and patient portals, fill prescriptions electronically, and have waiting rooms with WiFi or devices for children’s use. Office visits share space with providers’ desktops, laptops, and smartphones, with EMRs guiding the visit. EMRs may come home for evening documentation. How does this affect provider digital well-being? How do you start the conversation with families about digital well-being?
The American Academy of Pediatrics recommends media screening be incorporated into routine pediatric care, with several tools available to support this. Adapting the HEADSSS model for psychosocial check-ins, Clark and colleagues propose an additional “S” to capture screen time.11 Their model queries which apps and social media are used, quantity of use, effects on self-confidence, and whether cyberbullying or sexting are occurring. Smartphones themselves provide an eye-opening and accessible dataset, with built-in features (for example, Screen Time for iOS) tracking not just daily duration of use, but also how frequently the phone is picked up and which apps get more use. Screening may be followed by motivational coaching, emphasizing nonjudgment, curiosity, empathy, and flexibility — for patient and provider.12
In Charlie’s case, screening reveals heavy use of social Internet games that connect him with like-minded peers. While he describes an inclusiveness and level of socialization that he has not found outside the home, the quantity of use is interfering with sleep, schoolwork, and physical activity.
Significant problematic Internet use may lead to intervention or referral – addictive behaviors and mental health symptoms may warrant connection with mental health providers. Cyberbullying or unsafe behaviors may additionally benefit from parental and school-based support. There is early and limited evidence that psychological and educational interventions may be of benefit for problematic Internet use.13
When digital life is not so dramatically affecting well-being, providers may begin by working with families on a media use plan. The AAP offers its own website to support this. Other well-researched and well-designed sites include Digital Wellness Lab For Parents, with developmentally staged information and plentiful research, and Common Sense Media, which reviews apps, movies, and more; plus they have a knowledge/advice section under “Parents Need to Know.” Keep in mind that digital media can also support youth in managing psychiatric problems, e.g., a digital intervention promoting positive psychology practices looked very helpful for young people with psychosis.14
For Charlie, a health coaching approach is adopted. Using Gabrielli’s TECH parenting rubric,15 Charlie’s parents are coached to make space to talk about and coview media and apps, as well as creating a Family Media Use Plan for everyone – parents included. Alongside setting limits on screen time; health promotion activities like exercise, reading, and schoolwork are also rewarded with extra screen time. When Charlie returns 3 months later, the family reports that, in recognition of their collective digital overload, they preserved dinnertime and after 10 p.m. as screen-free downtime. While they still have concerns about Charlie’s gaming and social life, his sleep is somewhat improved and family tension is lower.
Attention to digital well-being stands to benefit provider and patient alike, and over time may gain from the scaffolding of handouts, standardized assessments, and health coaching providers that may be in place to support other important domains like sleep hygiene, food security, and parenting.
Dr. Rosenfeld is assistant professor, University of Vermont, Vermont Center for Children, Youth, and Families, Burlington. He has no relevant disclosures.
References
1. Chassiakos YR et al. Pediatrics. 2016;138(5)e20162593.
2. Orben A. Soc Psychiatry Psych Epi. 2020;55(4):407.
3. Fang K et al. Child Care Health Dev. 2019;45(5):744-53.
4. Janssen X et al. Sleep Med Rev. 2020;49:101226.
5. George MJ et al. J Ped. 2020;219:180.
6. Twenge JM and Campbell WK. Psychiatry Q. 2019;90(2):311-31.
7. Twenge JM and Martin GN. J Adolesc. 2020;79:91.
8. Efraim M et al. Brain Imaging Behav. 2021;15(1):177-89.
9. Hutton JS et al. JAMA Pediatr. 2020;174(1):e193869.
10. Hutton JS et al. Acta Paediatr. 2020;109(7):1376-86.
11. Clark DL et al. Pediatrics. 2018;141(6).
12. Jericho M and Elliot A. Clin Child Psychol Psychiatry. 2020;25(3):662.
13. Malinauskas R and Malinauskine V. J Behav Addict. 2019;8(4):613.
14. Lim MH et al. Soc Psychiatry Psychiatr Epi. 2020;55(7):877-89.
15. Gabrielli J et al. Pediatrics. 2018;142(1)e20173718.
Charlie is a 15-year-old male whose medical history includes overweight and autism spectrum disorder. While his autism symptoms are stable and he is doing fairly well in school, your sense is that he is underperforming and unhappy. His screening for anxiety and depression is not outstanding and you wonder whether to leave well enough alone.
Historically, pediatrician queries about media use happen in a minority of visits,1 overcrowded by the multitude of screening and acute care needs, let alone the pressures of electronic health record prompts, billing, and documentation. Yet the COVID-19 pandemic has emphasized what was already getting louder: screen life is becoming a ubiquitous, increasing, and normative function of child development. Digital well-being exhibits bidirectional interactions with most of the core indicators of child health: sleep, nutrition, safety, mood, relationships, and many other aspects of physical and mental health.1
The pandemic unveiled the blessings and curses of digital life by shifting many into remote work and school situations where screen time became both necessary and uncontrollable. Reeling with changes in employment, health, finances, and more, families struggled to forge a new screen-life balance that could bridge academic, professional, and recreational use.
Research has wavered in producing a verdict on the effects of screen time, in part because of limitations in methodology and follow-up time,2 and exacerbated by the quickly changing nature of screen use. Screen time may put youth at risk for obesity and behavior problems,3 but the latter may be mediated in part by loss of sleep because of late-night digital activity.4 While survey data at the population level show little link between screen time and well-being impairments,5 zooming in on individuals may tell a different story. Twenge and Campbell show light use of digital media (compared with nonuse) is associated with greater well-being while heavy use is associated with lower well-being and a higher risk for depression and suicidal behavior – especially in girls.6,7 Largely cross-sectional data show a small detriment to psychological well-being associated with digital technology, though this may be bidirectional and does not clearly differentiate types of technology.2
Recent neuroscience suggests that, compared with active play, sedentary screen time after school reduced impulse control and increased brain activity in regions associated with craving.8 This may explain some of the link between screen time and obesity. Brain imaging of preschoolers showed that greater screen time correlated with lower reading readiness as well as less integrity of white-matter tracts involved in language and executive function,9 whereas nurturing home reading practices were protective for language development and white matter integrity.10
Returning to the care of Charlie, providers may benefit from taking time to reflect on their own digital environment. What does the patient-side view of your office look like? Many offices use telephone reminders and patient portals, fill prescriptions electronically, and have waiting rooms with WiFi or devices for children’s use. Office visits share space with providers’ desktops, laptops, and smartphones, with EMRs guiding the visit. EMRs may come home for evening documentation. How does this affect provider digital well-being? How do you start the conversation with families about digital well-being?
The American Academy of Pediatrics recommends media screening be incorporated into routine pediatric care, with several tools available to support this. Adapting the HEADSSS model for psychosocial check-ins, Clark and colleagues propose an additional “S” to capture screen time.11 Their model queries which apps and social media are used, quantity of use, effects on self-confidence, and whether cyberbullying or sexting are occurring. Smartphones themselves provide an eye-opening and accessible dataset, with built-in features (for example, Screen Time for iOS) tracking not just daily duration of use, but also how frequently the phone is picked up and which apps get more use. Screening may be followed by motivational coaching, emphasizing nonjudgment, curiosity, empathy, and flexibility — for patient and provider.12
In Charlie’s case, screening reveals heavy use of social Internet games that connect him with like-minded peers. While he describes an inclusiveness and level of socialization that he has not found outside the home, the quantity of use is interfering with sleep, schoolwork, and physical activity.
Significant problematic Internet use may lead to intervention or referral – addictive behaviors and mental health symptoms may warrant connection with mental health providers. Cyberbullying or unsafe behaviors may additionally benefit from parental and school-based support. There is early and limited evidence that psychological and educational interventions may be of benefit for problematic Internet use.13
When digital life is not so dramatically affecting well-being, providers may begin by working with families on a media use plan. The AAP offers its own website to support this. Other well-researched and well-designed sites include Digital Wellness Lab For Parents, with developmentally staged information and plentiful research, and Common Sense Media, which reviews apps, movies, and more; plus they have a knowledge/advice section under “Parents Need to Know.” Keep in mind that digital media can also support youth in managing psychiatric problems, e.g., a digital intervention promoting positive psychology practices looked very helpful for young people with psychosis.14
For Charlie, a health coaching approach is adopted. Using Gabrielli’s TECH parenting rubric,15 Charlie’s parents are coached to make space to talk about and coview media and apps, as well as creating a Family Media Use Plan for everyone – parents included. Alongside setting limits on screen time; health promotion activities like exercise, reading, and schoolwork are also rewarded with extra screen time. When Charlie returns 3 months later, the family reports that, in recognition of their collective digital overload, they preserved dinnertime and after 10 p.m. as screen-free downtime. While they still have concerns about Charlie’s gaming and social life, his sleep is somewhat improved and family tension is lower.
Attention to digital well-being stands to benefit provider and patient alike, and over time may gain from the scaffolding of handouts, standardized assessments, and health coaching providers that may be in place to support other important domains like sleep hygiene, food security, and parenting.
Dr. Rosenfeld is assistant professor, University of Vermont, Vermont Center for Children, Youth, and Families, Burlington. He has no relevant disclosures.
References
1. Chassiakos YR et al. Pediatrics. 2016;138(5)e20162593.
2. Orben A. Soc Psychiatry Psych Epi. 2020;55(4):407.
3. Fang K et al. Child Care Health Dev. 2019;45(5):744-53.
4. Janssen X et al. Sleep Med Rev. 2020;49:101226.
5. George MJ et al. J Ped. 2020;219:180.
6. Twenge JM and Campbell WK. Psychiatry Q. 2019;90(2):311-31.
7. Twenge JM and Martin GN. J Adolesc. 2020;79:91.
8. Efraim M et al. Brain Imaging Behav. 2021;15(1):177-89.
9. Hutton JS et al. JAMA Pediatr. 2020;174(1):e193869.
10. Hutton JS et al. Acta Paediatr. 2020;109(7):1376-86.
11. Clark DL et al. Pediatrics. 2018;141(6).
12. Jericho M and Elliot A. Clin Child Psychol Psychiatry. 2020;25(3):662.
13. Malinauskas R and Malinauskine V. J Behav Addict. 2019;8(4):613.
14. Lim MH et al. Soc Psychiatry Psychiatr Epi. 2020;55(7):877-89.
15. Gabrielli J et al. Pediatrics. 2018;142(1)e20173718.
Is your patient having an existential crisis?
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.
Reporting Biopsy Margin Status for Cutaneous Basal Cell Carcinoma: To Do or Not to Do
To the Editor:
In an interesting analysis, Brady and Hossler1 (Cutis. 2020;106:315-317) highlighted the limitations of histopathologic biopsy margin evaluation for cutaneous basal cell carcinoma (BCC). Taking into consideration the high prevalence of BCC and its medical and economic impact on the health care system, the issue raised by the authors is an important one. They proposed that pathologists may omit reporting margins or clarify the limitations in their reports. It is a valid suggestion; however, in practice, margin evaluation is not always a simple process and is influenced by a number of factors.
The subject of optimum margins for BCC has been debated over decades now; however, ambiguity and lack of definitive guidelines on certain aspects still remain, leading to a lack of standardization and variability in reporting, which opens potential for error. In anatomical pathology, the biopsies for malignancies are interpreted to confirm diagnosis and perform risk assessment, with evaluation of margins generally reserved for subsequent definitive resections. Typically, margins are not required by clinicians or reported by pathologists in common endoscopic (eg, stomach, colon) or needle core (eg, prostate, breast) biopsies. Skin holds a rather unique position in which margin evaluation is not just limited to excisions. With the exception of samples generated from electrodesiccation and curettage, it is common practice by some laboratories to report margins on most specimens of cutaneous malignancies.
In simple terms, when margins are labeled negative there should be no residual disease, and when they are deemed positive there should be disease still persisting in the patient. Margin evaluation for BCC on biopsies falls short on both fronts. In one analysis, 24% (34/143) of shave biopsies reported with negative margins displayed residual BCC in ensuing re-excisions (negative predictive value: 76%).2 Standard bread-loafing, en-face margins and inking for orientation utilized to provide a thorough margin evaluation of excisions cannot be optimally achieved on small skin biopsies. Microscopic sections for analysis are 2-dimensional representations of 3-dimensional structures. Slides prepared can miss deeply embedded outermost margins, positioned parallel to the plane of sectioning, thereby creating blind spots where margins cannot be precisely assessed and generating an inherent limitation in evaluation. Exhaustive deeper levels done routinely can address this issue to a certain degree; however, it can be an impractical solution with cost implications and delay in turnaround time.
Conversely, it also is common to encounter absence of residual BCC in re-excisions in which the original biopsy margins were labeled positive. In one analysis, 49% of BCC patients (n=100) with positive biopsy margins did not display residual neoplasm on following re-excisions.3 Localized biopsy site immune response as a cause of postbiopsy regression of residual tumor has been hypothesized to produce this phenomenon. Moreover, initial biopsies may eliminate the majority of the tumor with only minimal disease persisting. Re-excisions submitted in toto allow for a systematic examination; however, areas in between sections still remain where minute residual tumor may hide. Searching for such occult foci generally is not aggressively pursued via deeper levels unless the margins of re-excision are in question.
Superficial-type BCC (or superficial multifocal BCC) is a major factor in precluding precise biopsy margin evaluation. In a study where initial biopsies reported with negative margins displayed residual BCC in subsequent re-excisions, 91% (31/34) of residual BCCs were of superficial variety.2 Clinically, superficial BCC frequently has indistinct borders with subtle subclinical peripheral progression. It has a tendency to expand radially, with the clinical appearance deceptively smaller than its true extent. In a plane of histopathologic section, superficial BCC may exhibit skip zones within the epidermis. Even though the margin may seem uninvolved on the slide, a noncontiguous focus may still emerge beyond the “negative” margin. Because superficial pattern is not unusual as one of the components of mixed histology (composite) BCC, this issue is not just limited to tumors specifically designated as superficial type.4
The intent of a procedure is important to recognize. If a biopsy is done with the intention of diagnosis only, the pathologic assessment can be limited to tumor identification and core data elements, with margin evaluation reserved for excisions done with therapeutic intent. However, the intent is not always clear, which adds to ambiguity on when to report margins. It is not uncommon to find saucerization shaves or large punch biopsies for BCC carried out with a therapeutic intent. The status of margin is desired in such samples; however, the intent is not always clearly communicated on requisitions. To avoid any gaps in communication, some pathologists may err on the side of caution and start routinely reporting margins on biopsies.
Taking into account the inaccuracy of margin assessment in biopsies, an argument for omitting margin reporting is plausible. Although dermatologists are the major contributors of skin samples, pathology laboratories cater to a broader clientele. Other physicians from different surgical and medical specialities also perform skin biopsies, and catering to a variety of specialities adds another layer of complexity. A dermatologist may appreciate the debate regarding reliability of margins; however, a physician from another speciality who is not as familiar with the diseases of the integument may lack proper understanding. Omitting margin reporting may lead to misinterpretations or false assumptions, such as, “The margins must be uninvolved, otherwise the pathologist would have said something.” This also can generate additional phone or email inquiries and second review requests. Rather than completely omitting them, another strategy can be to report margins in more quantitative terms. One reporting approach is to have 3 categories of involved, uninvolved, and uninvolved but close for margins less than 1 mm. The cases in the third category may require greater scrutiny by deeper levels or an added caveat in the comment addressing the limitation. If the status of margins is not reported due to a certain reason, a short comment can be added to explain the reason.
In sum, clinicians should recognize that “margin negative” on skin biopsy does not always equate to “completely excised.” Margin status on biopsies is a data item that essentially provides a probability of margin clearance. Completely omitting the margin status on all biopsies may not be the most prudent approach; however, improved guidelines and modifications to enhance the reporting are definitely required.
References
- Brady MC, Hossler EW. Reliability of biopsy margin status for basal cell carcinoma: a retrospective study. Cutis. 2020;106:315-317.
- Willardson HB, Lombardo J, Raines M, et al. Predictive value of basal cell carcinoma biopsies with negative margins: a retrospective cohort study. J Am Acad Dermatol. 2018;79:42-46.
- Yuan Y, Duff ML, Sammons DL, et al. Retrospective chart review of skin cancer presence in the wide excisions. World J Clin Cases. 2014;2:52-56.
- Cohen PR, Schulze KE, Nelson BR. Basal cell carcinoma with mixed histology: a possible pathogenesis for recurrent skin cancer. Dermatol Surg. 2006;32:542-551.
Continue to: Author's Response...
Authors’ Response
We appreciate the thorough and thoughtful comments in the Letter to the Editor. We agree with the author’s assertion that negative margins on skin specimens does not equate to “completely excised” and that the intent of the clinician is not always clear, even when the pathologist has ready access to the clinician’s notes, as was the case for the majority of specimens included in our study.
There is already variability in how pathologists report margins, including the specific verbiage used, at least for melanocytic lesions.1 The choice of whether or not to report margins and the meaning of those margins is complex due to the uncertainty inherent in margin assessment. Quantifying this uncertainty was the main reason for our study. Ultimately, the pathologist’s decision on whether and how to report margins should be focused on improving patient outcomes. There are benefits and drawbacks to all approaches, and our goal is to provide more information for clinicians and pathologists so that they may better care for their patients. Understanding the limitations of margins on submitted skin specimens—whether margins are reported or not—can only serve to guide improve clinical decision-making.
We also agree that the breadth of specialties of submitting clinicians make reporting of margins difficult, and there is likely similar breadth in their understanding of the nuances of margin assessment and reports. The solution to this problem is adequate education regarding the limitations of a pathology report, and specifically what is meant when margins are (or are not) reported on skin specimens. How to best educate the myriad clinicians who submit biopsies is, of course, the ultimate challenge.
We hope that our study adds information to this ongoing debate regarding margin status reporting, and we appreciate the discussion points raised by the author.
Eric Hossler, MD; Mary Brady, MD
From the Department of Dermatology, Geisinger Health System, Danville, Pennsylvania.
The authors report no conflict of interest.
Reference
- Sellheyer K, Bergfeld WF, Stewart E, et al. Evaluation of surgical margins in melanocytic lesions: a survey among 152 dermatopathologists.J Cutan Pathol. 2005;32:293-299.
To the Editor:
In an interesting analysis, Brady and Hossler1 (Cutis. 2020;106:315-317) highlighted the limitations of histopathologic biopsy margin evaluation for cutaneous basal cell carcinoma (BCC). Taking into consideration the high prevalence of BCC and its medical and economic impact on the health care system, the issue raised by the authors is an important one. They proposed that pathologists may omit reporting margins or clarify the limitations in their reports. It is a valid suggestion; however, in practice, margin evaluation is not always a simple process and is influenced by a number of factors.
The subject of optimum margins for BCC has been debated over decades now; however, ambiguity and lack of definitive guidelines on certain aspects still remain, leading to a lack of standardization and variability in reporting, which opens potential for error. In anatomical pathology, the biopsies for malignancies are interpreted to confirm diagnosis and perform risk assessment, with evaluation of margins generally reserved for subsequent definitive resections. Typically, margins are not required by clinicians or reported by pathologists in common endoscopic (eg, stomach, colon) or needle core (eg, prostate, breast) biopsies. Skin holds a rather unique position in which margin evaluation is not just limited to excisions. With the exception of samples generated from electrodesiccation and curettage, it is common practice by some laboratories to report margins on most specimens of cutaneous malignancies.
In simple terms, when margins are labeled negative there should be no residual disease, and when they are deemed positive there should be disease still persisting in the patient. Margin evaluation for BCC on biopsies falls short on both fronts. In one analysis, 24% (34/143) of shave biopsies reported with negative margins displayed residual BCC in ensuing re-excisions (negative predictive value: 76%).2 Standard bread-loafing, en-face margins and inking for orientation utilized to provide a thorough margin evaluation of excisions cannot be optimally achieved on small skin biopsies. Microscopic sections for analysis are 2-dimensional representations of 3-dimensional structures. Slides prepared can miss deeply embedded outermost margins, positioned parallel to the plane of sectioning, thereby creating blind spots where margins cannot be precisely assessed and generating an inherent limitation in evaluation. Exhaustive deeper levels done routinely can address this issue to a certain degree; however, it can be an impractical solution with cost implications and delay in turnaround time.
Conversely, it also is common to encounter absence of residual BCC in re-excisions in which the original biopsy margins were labeled positive. In one analysis, 49% of BCC patients (n=100) with positive biopsy margins did not display residual neoplasm on following re-excisions.3 Localized biopsy site immune response as a cause of postbiopsy regression of residual tumor has been hypothesized to produce this phenomenon. Moreover, initial biopsies may eliminate the majority of the tumor with only minimal disease persisting. Re-excisions submitted in toto allow for a systematic examination; however, areas in between sections still remain where minute residual tumor may hide. Searching for such occult foci generally is not aggressively pursued via deeper levels unless the margins of re-excision are in question.
Superficial-type BCC (or superficial multifocal BCC) is a major factor in precluding precise biopsy margin evaluation. In a study where initial biopsies reported with negative margins displayed residual BCC in subsequent re-excisions, 91% (31/34) of residual BCCs were of superficial variety.2 Clinically, superficial BCC frequently has indistinct borders with subtle subclinical peripheral progression. It has a tendency to expand radially, with the clinical appearance deceptively smaller than its true extent. In a plane of histopathologic section, superficial BCC may exhibit skip zones within the epidermis. Even though the margin may seem uninvolved on the slide, a noncontiguous focus may still emerge beyond the “negative” margin. Because superficial pattern is not unusual as one of the components of mixed histology (composite) BCC, this issue is not just limited to tumors specifically designated as superficial type.4
The intent of a procedure is important to recognize. If a biopsy is done with the intention of diagnosis only, the pathologic assessment can be limited to tumor identification and core data elements, with margin evaluation reserved for excisions done with therapeutic intent. However, the intent is not always clear, which adds to ambiguity on when to report margins. It is not uncommon to find saucerization shaves or large punch biopsies for BCC carried out with a therapeutic intent. The status of margin is desired in such samples; however, the intent is not always clearly communicated on requisitions. To avoid any gaps in communication, some pathologists may err on the side of caution and start routinely reporting margins on biopsies.
Taking into account the inaccuracy of margin assessment in biopsies, an argument for omitting margin reporting is plausible. Although dermatologists are the major contributors of skin samples, pathology laboratories cater to a broader clientele. Other physicians from different surgical and medical specialities also perform skin biopsies, and catering to a variety of specialities adds another layer of complexity. A dermatologist may appreciate the debate regarding reliability of margins; however, a physician from another speciality who is not as familiar with the diseases of the integument may lack proper understanding. Omitting margin reporting may lead to misinterpretations or false assumptions, such as, “The margins must be uninvolved, otherwise the pathologist would have said something.” This also can generate additional phone or email inquiries and second review requests. Rather than completely omitting them, another strategy can be to report margins in more quantitative terms. One reporting approach is to have 3 categories of involved, uninvolved, and uninvolved but close for margins less than 1 mm. The cases in the third category may require greater scrutiny by deeper levels or an added caveat in the comment addressing the limitation. If the status of margins is not reported due to a certain reason, a short comment can be added to explain the reason.
In sum, clinicians should recognize that “margin negative” on skin biopsy does not always equate to “completely excised.” Margin status on biopsies is a data item that essentially provides a probability of margin clearance. Completely omitting the margin status on all biopsies may not be the most prudent approach; however, improved guidelines and modifications to enhance the reporting are definitely required.
References
- Brady MC, Hossler EW. Reliability of biopsy margin status for basal cell carcinoma: a retrospective study. Cutis. 2020;106:315-317.
- Willardson HB, Lombardo J, Raines M, et al. Predictive value of basal cell carcinoma biopsies with negative margins: a retrospective cohort study. J Am Acad Dermatol. 2018;79:42-46.
- Yuan Y, Duff ML, Sammons DL, et al. Retrospective chart review of skin cancer presence in the wide excisions. World J Clin Cases. 2014;2:52-56.
- Cohen PR, Schulze KE, Nelson BR. Basal cell carcinoma with mixed histology: a possible pathogenesis for recurrent skin cancer. Dermatol Surg. 2006;32:542-551.
Continue to: Author's Response...
Authors’ Response
We appreciate the thorough and thoughtful comments in the Letter to the Editor. We agree with the author’s assertion that negative margins on skin specimens does not equate to “completely excised” and that the intent of the clinician is not always clear, even when the pathologist has ready access to the clinician’s notes, as was the case for the majority of specimens included in our study.
There is already variability in how pathologists report margins, including the specific verbiage used, at least for melanocytic lesions.1 The choice of whether or not to report margins and the meaning of those margins is complex due to the uncertainty inherent in margin assessment. Quantifying this uncertainty was the main reason for our study. Ultimately, the pathologist’s decision on whether and how to report margins should be focused on improving patient outcomes. There are benefits and drawbacks to all approaches, and our goal is to provide more information for clinicians and pathologists so that they may better care for their patients. Understanding the limitations of margins on submitted skin specimens—whether margins are reported or not—can only serve to guide improve clinical decision-making.
We also agree that the breadth of specialties of submitting clinicians make reporting of margins difficult, and there is likely similar breadth in their understanding of the nuances of margin assessment and reports. The solution to this problem is adequate education regarding the limitations of a pathology report, and specifically what is meant when margins are (or are not) reported on skin specimens. How to best educate the myriad clinicians who submit biopsies is, of course, the ultimate challenge.
We hope that our study adds information to this ongoing debate regarding margin status reporting, and we appreciate the discussion points raised by the author.
Eric Hossler, MD; Mary Brady, MD
From the Department of Dermatology, Geisinger Health System, Danville, Pennsylvania.
The authors report no conflict of interest.
Reference
- Sellheyer K, Bergfeld WF, Stewart E, et al. Evaluation of surgical margins in melanocytic lesions: a survey among 152 dermatopathologists.J Cutan Pathol. 2005;32:293-299.
To the Editor:
In an interesting analysis, Brady and Hossler1 (Cutis. 2020;106:315-317) highlighted the limitations of histopathologic biopsy margin evaluation for cutaneous basal cell carcinoma (BCC). Taking into consideration the high prevalence of BCC and its medical and economic impact on the health care system, the issue raised by the authors is an important one. They proposed that pathologists may omit reporting margins or clarify the limitations in their reports. It is a valid suggestion; however, in practice, margin evaluation is not always a simple process and is influenced by a number of factors.
The subject of optimum margins for BCC has been debated over decades now; however, ambiguity and lack of definitive guidelines on certain aspects still remain, leading to a lack of standardization and variability in reporting, which opens potential for error. In anatomical pathology, the biopsies for malignancies are interpreted to confirm diagnosis and perform risk assessment, with evaluation of margins generally reserved for subsequent definitive resections. Typically, margins are not required by clinicians or reported by pathologists in common endoscopic (eg, stomach, colon) or needle core (eg, prostate, breast) biopsies. Skin holds a rather unique position in which margin evaluation is not just limited to excisions. With the exception of samples generated from electrodesiccation and curettage, it is common practice by some laboratories to report margins on most specimens of cutaneous malignancies.
In simple terms, when margins are labeled negative there should be no residual disease, and when they are deemed positive there should be disease still persisting in the patient. Margin evaluation for BCC on biopsies falls short on both fronts. In one analysis, 24% (34/143) of shave biopsies reported with negative margins displayed residual BCC in ensuing re-excisions (negative predictive value: 76%).2 Standard bread-loafing, en-face margins and inking for orientation utilized to provide a thorough margin evaluation of excisions cannot be optimally achieved on small skin biopsies. Microscopic sections for analysis are 2-dimensional representations of 3-dimensional structures. Slides prepared can miss deeply embedded outermost margins, positioned parallel to the plane of sectioning, thereby creating blind spots where margins cannot be precisely assessed and generating an inherent limitation in evaluation. Exhaustive deeper levels done routinely can address this issue to a certain degree; however, it can be an impractical solution with cost implications and delay in turnaround time.
Conversely, it also is common to encounter absence of residual BCC in re-excisions in which the original biopsy margins were labeled positive. In one analysis, 49% of BCC patients (n=100) with positive biopsy margins did not display residual neoplasm on following re-excisions.3 Localized biopsy site immune response as a cause of postbiopsy regression of residual tumor has been hypothesized to produce this phenomenon. Moreover, initial biopsies may eliminate the majority of the tumor with only minimal disease persisting. Re-excisions submitted in toto allow for a systematic examination; however, areas in between sections still remain where minute residual tumor may hide. Searching for such occult foci generally is not aggressively pursued via deeper levels unless the margins of re-excision are in question.
Superficial-type BCC (or superficial multifocal BCC) is a major factor in precluding precise biopsy margin evaluation. In a study where initial biopsies reported with negative margins displayed residual BCC in subsequent re-excisions, 91% (31/34) of residual BCCs were of superficial variety.2 Clinically, superficial BCC frequently has indistinct borders with subtle subclinical peripheral progression. It has a tendency to expand radially, with the clinical appearance deceptively smaller than its true extent. In a plane of histopathologic section, superficial BCC may exhibit skip zones within the epidermis. Even though the margin may seem uninvolved on the slide, a noncontiguous focus may still emerge beyond the “negative” margin. Because superficial pattern is not unusual as one of the components of mixed histology (composite) BCC, this issue is not just limited to tumors specifically designated as superficial type.4
The intent of a procedure is important to recognize. If a biopsy is done with the intention of diagnosis only, the pathologic assessment can be limited to tumor identification and core data elements, with margin evaluation reserved for excisions done with therapeutic intent. However, the intent is not always clear, which adds to ambiguity on when to report margins. It is not uncommon to find saucerization shaves or large punch biopsies for BCC carried out with a therapeutic intent. The status of margin is desired in such samples; however, the intent is not always clearly communicated on requisitions. To avoid any gaps in communication, some pathologists may err on the side of caution and start routinely reporting margins on biopsies.
Taking into account the inaccuracy of margin assessment in biopsies, an argument for omitting margin reporting is plausible. Although dermatologists are the major contributors of skin samples, pathology laboratories cater to a broader clientele. Other physicians from different surgical and medical specialities also perform skin biopsies, and catering to a variety of specialities adds another layer of complexity. A dermatologist may appreciate the debate regarding reliability of margins; however, a physician from another speciality who is not as familiar with the diseases of the integument may lack proper understanding. Omitting margin reporting may lead to misinterpretations or false assumptions, such as, “The margins must be uninvolved, otherwise the pathologist would have said something.” This also can generate additional phone or email inquiries and second review requests. Rather than completely omitting them, another strategy can be to report margins in more quantitative terms. One reporting approach is to have 3 categories of involved, uninvolved, and uninvolved but close for margins less than 1 mm. The cases in the third category may require greater scrutiny by deeper levels or an added caveat in the comment addressing the limitation. If the status of margins is not reported due to a certain reason, a short comment can be added to explain the reason.
In sum, clinicians should recognize that “margin negative” on skin biopsy does not always equate to “completely excised.” Margin status on biopsies is a data item that essentially provides a probability of margin clearance. Completely omitting the margin status on all biopsies may not be the most prudent approach; however, improved guidelines and modifications to enhance the reporting are definitely required.
References
- Brady MC, Hossler EW. Reliability of biopsy margin status for basal cell carcinoma: a retrospective study. Cutis. 2020;106:315-317.
- Willardson HB, Lombardo J, Raines M, et al. Predictive value of basal cell carcinoma biopsies with negative margins: a retrospective cohort study. J Am Acad Dermatol. 2018;79:42-46.
- Yuan Y, Duff ML, Sammons DL, et al. Retrospective chart review of skin cancer presence in the wide excisions. World J Clin Cases. 2014;2:52-56.
- Cohen PR, Schulze KE, Nelson BR. Basal cell carcinoma with mixed histology: a possible pathogenesis for recurrent skin cancer. Dermatol Surg. 2006;32:542-551.
Continue to: Author's Response...
Authors’ Response
We appreciate the thorough and thoughtful comments in the Letter to the Editor. We agree with the author’s assertion that negative margins on skin specimens does not equate to “completely excised” and that the intent of the clinician is not always clear, even when the pathologist has ready access to the clinician’s notes, as was the case for the majority of specimens included in our study.
There is already variability in how pathologists report margins, including the specific verbiage used, at least for melanocytic lesions.1 The choice of whether or not to report margins and the meaning of those margins is complex due to the uncertainty inherent in margin assessment. Quantifying this uncertainty was the main reason for our study. Ultimately, the pathologist’s decision on whether and how to report margins should be focused on improving patient outcomes. There are benefits and drawbacks to all approaches, and our goal is to provide more information for clinicians and pathologists so that they may better care for their patients. Understanding the limitations of margins on submitted skin specimens—whether margins are reported or not—can only serve to guide improve clinical decision-making.
We also agree that the breadth of specialties of submitting clinicians make reporting of margins difficult, and there is likely similar breadth in their understanding of the nuances of margin assessment and reports. The solution to this problem is adequate education regarding the limitations of a pathology report, and specifically what is meant when margins are (or are not) reported on skin specimens. How to best educate the myriad clinicians who submit biopsies is, of course, the ultimate challenge.
We hope that our study adds information to this ongoing debate regarding margin status reporting, and we appreciate the discussion points raised by the author.
Eric Hossler, MD; Mary Brady, MD
From the Department of Dermatology, Geisinger Health System, Danville, Pennsylvania.
The authors report no conflict of interest.
Reference
- Sellheyer K, Bergfeld WF, Stewart E, et al. Evaluation of surgical margins in melanocytic lesions: a survey among 152 dermatopathologists.J Cutan Pathol. 2005;32:293-299.
Updates in clinical practice guidelines for Lyme disease
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
Mistrust and Mandates: COVID-19 Vaccination in the Military
It is June and most of us are looking forward to a more normal summer than the one we had in 2020. Many Americans have been vaccinated and states are rolling back some (or all) masking requirements and restrictions on gatherings. In many sectors, including the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA), worries from public health officials about vaccine supply and how to ethically allocate demand have given way to a new set of concerns: We have the shots, but for widespread protection we have to get them into arms.
The reluctance to roll up the sleeve is known as vaccine hesitancy. The National Academies of Science comments on vaccine hesitancy in its report on COVID-19 vaccination allocation. “Potential consequences of vaccine hesitancy—which the committee views as an attitude, preference, or motivational state—are the behaviors of vaccine refusal or delay.”2
On that count, there was encouraging albeit unexpected news in waning days of May. Media reported a sharp increase in the COVID-vaccination of military personnel. Unnamed DoD officials indicated, they had seen a 55% increase in the vaccination of active-duty service members over the previous month. This news represents a dramatic turnaround in a trend of vaccine hesitancy among military members that has persisted since the vaccine became available.3 Even last month, this would have been a very different column. The DoD has not disclosed the exact number of service members who have declined COVID-19 vaccination but multiple news outlets have documented that there was widespread and significant vaccine hesitancy among military personnel. In February, Military News reported that one-third of troops who were offered the vaccine declined it; and in April, USA Today stated that 40% of Marines had refused vaccination.4,5
Still, it is worth examining the data on vaccination among active duty service members. From December 2020 through March 2021, the military conducted the first study to evaluate rates of vaccine initiation and completion in the military in general and for service members from racial/ethnic minorities in particular. Black military personnel were 28% less likely than non-Hispanic White service members to initiate vaccination against coronavirus even after adjusting for other possible confounders. Just 29% of White, 25.5% of Hispanic, and 18.7% of Black service members had initiated the vaccine process in the survey.6
The authors suggest that in part, vaccine hesitancy explains the findings.4 Vaccine hesitancy among racial and ethnic minorities is even more tragic because these same already disadvantaged cohorts have disproportionately suffered from COVID-19 throughout the pandemic with higher rates of infection, serious illness requiring hospitalization, and infection-related morbidity.7
Vaccine hesitancy, delay, or refusal in Black Americans whether military or civilian often is attributed to the historical abuses like the Tuskegee syphilis experiments or the more recent example of cancer cell lines taken from Henrietta Lacks without consent.8 Such government sponsored betrayals no doubt are the soil in which hesitancy grows but recent commentators have opined that focusing solely on these infamous examples may ignore current systemic racism that is pervasively feeding Black Americans reluctance to consider or accept COVID-19 vaccination.9 Blaming infamous research also provides a convenient excuse for confronting contemporary racial discrimination in health care and taking responsibility as health care practitioners for reversing it. “Framing the conversation about distrust in COVID vaccines in terms of everyday racism rather than historical atrocities may increase underserved communities’ willingness to be vaccinated,” Bajaj and Stanford wrote in a recent recent New England Journal of Medicine commentary. “When we hyperfocus on Sims, Lacks, and Tuskegee, we ascribe the current Black health experience to past racism, rooting our present in immovable historical occurrences and undermining efforts to combat mistrust. Everyday racism, by contrast, can be tackled in the present.”9
The study of racial/ethnic disparities in COVID-19 vaccination in active-duty service members was a work product of the Armed Forces Health Surveillance Division. The authors underscore several factors that support the connection between discrimination and vaccine hesitancy in the military. Lack of access to and ability to obtain COVID-19 vaccination continues to be a major barrier that disadvantaged populations must overcome.10 The COVID-19 vaccine is widely available, easily obtained, and free of charge for all military personnel. Yet the vaccine hesitancy in the military parallels that of the civilian sector. This led the study authors to opine that, “forces external to the U.S. Military, such as interpersonal and societal factors also contribute to vaccine hesitancy among military service members.”6
Obviously, any unvaccinated active-duty service member reduces the combat readiness of the fighting force a consideration that led some in Congress to call for mandating vaccination. The vaccine is currently being administered under an emergency use authorization (EUA), which prevents even the military from mandating it.11 Even if President Joseph Biden obtained a waiver to make the vaccine mandatory, the implications of forcing service members who have volunteered to serve their country is ethically problematic. Those problems are exponentially amplified when applied to members of ethnic and racial minorities who have a past and present of health disparities and discrimination. Respecting the decision of those in uniform to decline COVID-19 vaccination is the first and perhaps most important step to rebuilding the trust that is the most promising means of reducing vaccine hesitancy.
Part of the accountability we all bear for health care inequity and racism is to continue the work of this landmark study to better understand vaccine hesitancy among military and veteran cohorts, develop counseling and education that target those attitudes, beliefs, and motivations with education, counseling, and support. All of us can in some small measure follow the ethical mandate “to dispel rumors and provide facts to people” of Secretary Austin, a Black retired 4-star Army general.1
1. Garmone J. Secretary of Defense Addresses Vaccine Hesitancy in the Military. Published February 25, 2021. Accessed May 26, 2021. https://www.defense.gov/Explore/News/Article/Article/2516511/secretary-of-defense-addresses-vaccine-hesitancy-in-military/
2. National Academies of Sciences, Engineering, and Medicine. Framework for Equitable Allocation of COVID-19 Vaccine . The National Academies of Science; 2020:188. doi:10.17226/25917
3. Liebermann O. US military sees 55% jump in COVID-19 vaccinations over last month. Published May 20, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/05/20/politics/us-military-covid-vaccinations/index.html
4. Kime P. Almost one-third of us troops are refusing COVID-19 vaccines, officials Say. Published February 17, 2021. Accessed May 26, 2021. https://www.military.com/daily-news/2021/02/17/almost-one-third-of-us-troops-are-refusing-covid-vaccines-officials-say.html
5. Elbeshbishi S. Nearly 40% of Marines decline COVID-19 vaccine, prompting some Democrats to urge Biden to set mandate for the military. USA Today. April 10, 2021. Accessed May 26, 2021. https://www.usatoday.com/story/news/politics/2021/04/10/covid-vaccine-nearly-forty-percent-us-marines-decline/7173918002/
6. Lang MA, Stahlman S, Wells NY, et al. Disparities in COVID-19 vaccine initiation and completion among active component service members and health care personnel, 11 December 2020-12 March 2021. MSMR. 2021;28(4):2-9.
7. Webb Hooper M, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA . 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598
8. Kum D. Fueled by a history of mistreatment, Black Americans distrust the new COVID-19 vaccines. TIME. December 8, 2020. Accessed May 26, 2021.https://time.com/5925074/black-americans-covid-19-vaccine-distrust/
9. Bajaj SS, Stanford FC. Beyond Tuskegee - Vaccine Distrust and Everyday Racism. N Engl J Med. 2021;384(5):e12. doi:10.1056/NEJMpv2035827
10. Feldman N. Why Black and Latino people still lag on COVID-19 vaccines-and how to fix it. NPR. April 26, 2021. Accessed May 26, 2021. https://www.npr.org/sections/health-shots/2021/04/26/989962041/why-black-and-latino-people-still-lag-on-covid-vaccines-and-how-to-fix-it
11. Kaufman E. Lawmakers ask Biden to issue waiver to make COVID-19 vaccination mandatory of members of the military. Updated March 24, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/03/24/politics/congress-letter-military-vaccine/index.html
It is June and most of us are looking forward to a more normal summer than the one we had in 2020. Many Americans have been vaccinated and states are rolling back some (or all) masking requirements and restrictions on gatherings. In many sectors, including the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA), worries from public health officials about vaccine supply and how to ethically allocate demand have given way to a new set of concerns: We have the shots, but for widespread protection we have to get them into arms.
The reluctance to roll up the sleeve is known as vaccine hesitancy. The National Academies of Science comments on vaccine hesitancy in its report on COVID-19 vaccination allocation. “Potential consequences of vaccine hesitancy—which the committee views as an attitude, preference, or motivational state—are the behaviors of vaccine refusal or delay.”2
On that count, there was encouraging albeit unexpected news in waning days of May. Media reported a sharp increase in the COVID-vaccination of military personnel. Unnamed DoD officials indicated, they had seen a 55% increase in the vaccination of active-duty service members over the previous month. This news represents a dramatic turnaround in a trend of vaccine hesitancy among military members that has persisted since the vaccine became available.3 Even last month, this would have been a very different column. The DoD has not disclosed the exact number of service members who have declined COVID-19 vaccination but multiple news outlets have documented that there was widespread and significant vaccine hesitancy among military personnel. In February, Military News reported that one-third of troops who were offered the vaccine declined it; and in April, USA Today stated that 40% of Marines had refused vaccination.4,5
Still, it is worth examining the data on vaccination among active duty service members. From December 2020 through March 2021, the military conducted the first study to evaluate rates of vaccine initiation and completion in the military in general and for service members from racial/ethnic minorities in particular. Black military personnel were 28% less likely than non-Hispanic White service members to initiate vaccination against coronavirus even after adjusting for other possible confounders. Just 29% of White, 25.5% of Hispanic, and 18.7% of Black service members had initiated the vaccine process in the survey.6
The authors suggest that in part, vaccine hesitancy explains the findings.4 Vaccine hesitancy among racial and ethnic minorities is even more tragic because these same already disadvantaged cohorts have disproportionately suffered from COVID-19 throughout the pandemic with higher rates of infection, serious illness requiring hospitalization, and infection-related morbidity.7
Vaccine hesitancy, delay, or refusal in Black Americans whether military or civilian often is attributed to the historical abuses like the Tuskegee syphilis experiments or the more recent example of cancer cell lines taken from Henrietta Lacks without consent.8 Such government sponsored betrayals no doubt are the soil in which hesitancy grows but recent commentators have opined that focusing solely on these infamous examples may ignore current systemic racism that is pervasively feeding Black Americans reluctance to consider or accept COVID-19 vaccination.9 Blaming infamous research also provides a convenient excuse for confronting contemporary racial discrimination in health care and taking responsibility as health care practitioners for reversing it. “Framing the conversation about distrust in COVID vaccines in terms of everyday racism rather than historical atrocities may increase underserved communities’ willingness to be vaccinated,” Bajaj and Stanford wrote in a recent recent New England Journal of Medicine commentary. “When we hyperfocus on Sims, Lacks, and Tuskegee, we ascribe the current Black health experience to past racism, rooting our present in immovable historical occurrences and undermining efforts to combat mistrust. Everyday racism, by contrast, can be tackled in the present.”9
The study of racial/ethnic disparities in COVID-19 vaccination in active-duty service members was a work product of the Armed Forces Health Surveillance Division. The authors underscore several factors that support the connection between discrimination and vaccine hesitancy in the military. Lack of access to and ability to obtain COVID-19 vaccination continues to be a major barrier that disadvantaged populations must overcome.10 The COVID-19 vaccine is widely available, easily obtained, and free of charge for all military personnel. Yet the vaccine hesitancy in the military parallels that of the civilian sector. This led the study authors to opine that, “forces external to the U.S. Military, such as interpersonal and societal factors also contribute to vaccine hesitancy among military service members.”6
Obviously, any unvaccinated active-duty service member reduces the combat readiness of the fighting force a consideration that led some in Congress to call for mandating vaccination. The vaccine is currently being administered under an emergency use authorization (EUA), which prevents even the military from mandating it.11 Even if President Joseph Biden obtained a waiver to make the vaccine mandatory, the implications of forcing service members who have volunteered to serve their country is ethically problematic. Those problems are exponentially amplified when applied to members of ethnic and racial minorities who have a past and present of health disparities and discrimination. Respecting the decision of those in uniform to decline COVID-19 vaccination is the first and perhaps most important step to rebuilding the trust that is the most promising means of reducing vaccine hesitancy.
Part of the accountability we all bear for health care inequity and racism is to continue the work of this landmark study to better understand vaccine hesitancy among military and veteran cohorts, develop counseling and education that target those attitudes, beliefs, and motivations with education, counseling, and support. All of us can in some small measure follow the ethical mandate “to dispel rumors and provide facts to people” of Secretary Austin, a Black retired 4-star Army general.1
It is June and most of us are looking forward to a more normal summer than the one we had in 2020. Many Americans have been vaccinated and states are rolling back some (or all) masking requirements and restrictions on gatherings. In many sectors, including the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA), worries from public health officials about vaccine supply and how to ethically allocate demand have given way to a new set of concerns: We have the shots, but for widespread protection we have to get them into arms.
The reluctance to roll up the sleeve is known as vaccine hesitancy. The National Academies of Science comments on vaccine hesitancy in its report on COVID-19 vaccination allocation. “Potential consequences of vaccine hesitancy—which the committee views as an attitude, preference, or motivational state—are the behaviors of vaccine refusal or delay.”2
On that count, there was encouraging albeit unexpected news in waning days of May. Media reported a sharp increase in the COVID-vaccination of military personnel. Unnamed DoD officials indicated, they had seen a 55% increase in the vaccination of active-duty service members over the previous month. This news represents a dramatic turnaround in a trend of vaccine hesitancy among military members that has persisted since the vaccine became available.3 Even last month, this would have been a very different column. The DoD has not disclosed the exact number of service members who have declined COVID-19 vaccination but multiple news outlets have documented that there was widespread and significant vaccine hesitancy among military personnel. In February, Military News reported that one-third of troops who were offered the vaccine declined it; and in April, USA Today stated that 40% of Marines had refused vaccination.4,5
Still, it is worth examining the data on vaccination among active duty service members. From December 2020 through March 2021, the military conducted the first study to evaluate rates of vaccine initiation and completion in the military in general and for service members from racial/ethnic minorities in particular. Black military personnel were 28% less likely than non-Hispanic White service members to initiate vaccination against coronavirus even after adjusting for other possible confounders. Just 29% of White, 25.5% of Hispanic, and 18.7% of Black service members had initiated the vaccine process in the survey.6
The authors suggest that in part, vaccine hesitancy explains the findings.4 Vaccine hesitancy among racial and ethnic minorities is even more tragic because these same already disadvantaged cohorts have disproportionately suffered from COVID-19 throughout the pandemic with higher rates of infection, serious illness requiring hospitalization, and infection-related morbidity.7
Vaccine hesitancy, delay, or refusal in Black Americans whether military or civilian often is attributed to the historical abuses like the Tuskegee syphilis experiments or the more recent example of cancer cell lines taken from Henrietta Lacks without consent.8 Such government sponsored betrayals no doubt are the soil in which hesitancy grows but recent commentators have opined that focusing solely on these infamous examples may ignore current systemic racism that is pervasively feeding Black Americans reluctance to consider or accept COVID-19 vaccination.9 Blaming infamous research also provides a convenient excuse for confronting contemporary racial discrimination in health care and taking responsibility as health care practitioners for reversing it. “Framing the conversation about distrust in COVID vaccines in terms of everyday racism rather than historical atrocities may increase underserved communities’ willingness to be vaccinated,” Bajaj and Stanford wrote in a recent recent New England Journal of Medicine commentary. “When we hyperfocus on Sims, Lacks, and Tuskegee, we ascribe the current Black health experience to past racism, rooting our present in immovable historical occurrences and undermining efforts to combat mistrust. Everyday racism, by contrast, can be tackled in the present.”9
The study of racial/ethnic disparities in COVID-19 vaccination in active-duty service members was a work product of the Armed Forces Health Surveillance Division. The authors underscore several factors that support the connection between discrimination and vaccine hesitancy in the military. Lack of access to and ability to obtain COVID-19 vaccination continues to be a major barrier that disadvantaged populations must overcome.10 The COVID-19 vaccine is widely available, easily obtained, and free of charge for all military personnel. Yet the vaccine hesitancy in the military parallels that of the civilian sector. This led the study authors to opine that, “forces external to the U.S. Military, such as interpersonal and societal factors also contribute to vaccine hesitancy among military service members.”6
Obviously, any unvaccinated active-duty service member reduces the combat readiness of the fighting force a consideration that led some in Congress to call for mandating vaccination. The vaccine is currently being administered under an emergency use authorization (EUA), which prevents even the military from mandating it.11 Even if President Joseph Biden obtained a waiver to make the vaccine mandatory, the implications of forcing service members who have volunteered to serve their country is ethically problematic. Those problems are exponentially amplified when applied to members of ethnic and racial minorities who have a past and present of health disparities and discrimination. Respecting the decision of those in uniform to decline COVID-19 vaccination is the first and perhaps most important step to rebuilding the trust that is the most promising means of reducing vaccine hesitancy.
Part of the accountability we all bear for health care inequity and racism is to continue the work of this landmark study to better understand vaccine hesitancy among military and veteran cohorts, develop counseling and education that target those attitudes, beliefs, and motivations with education, counseling, and support. All of us can in some small measure follow the ethical mandate “to dispel rumors and provide facts to people” of Secretary Austin, a Black retired 4-star Army general.1
1. Garmone J. Secretary of Defense Addresses Vaccine Hesitancy in the Military. Published February 25, 2021. Accessed May 26, 2021. https://www.defense.gov/Explore/News/Article/Article/2516511/secretary-of-defense-addresses-vaccine-hesitancy-in-military/
2. National Academies of Sciences, Engineering, and Medicine. Framework for Equitable Allocation of COVID-19 Vaccine . The National Academies of Science; 2020:188. doi:10.17226/25917
3. Liebermann O. US military sees 55% jump in COVID-19 vaccinations over last month. Published May 20, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/05/20/politics/us-military-covid-vaccinations/index.html
4. Kime P. Almost one-third of us troops are refusing COVID-19 vaccines, officials Say. Published February 17, 2021. Accessed May 26, 2021. https://www.military.com/daily-news/2021/02/17/almost-one-third-of-us-troops-are-refusing-covid-vaccines-officials-say.html
5. Elbeshbishi S. Nearly 40% of Marines decline COVID-19 vaccine, prompting some Democrats to urge Biden to set mandate for the military. USA Today. April 10, 2021. Accessed May 26, 2021. https://www.usatoday.com/story/news/politics/2021/04/10/covid-vaccine-nearly-forty-percent-us-marines-decline/7173918002/
6. Lang MA, Stahlman S, Wells NY, et al. Disparities in COVID-19 vaccine initiation and completion among active component service members and health care personnel, 11 December 2020-12 March 2021. MSMR. 2021;28(4):2-9.
7. Webb Hooper M, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA . 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598
8. Kum D. Fueled by a history of mistreatment, Black Americans distrust the new COVID-19 vaccines. TIME. December 8, 2020. Accessed May 26, 2021.https://time.com/5925074/black-americans-covid-19-vaccine-distrust/
9. Bajaj SS, Stanford FC. Beyond Tuskegee - Vaccine Distrust and Everyday Racism. N Engl J Med. 2021;384(5):e12. doi:10.1056/NEJMpv2035827
10. Feldman N. Why Black and Latino people still lag on COVID-19 vaccines-and how to fix it. NPR. April 26, 2021. Accessed May 26, 2021. https://www.npr.org/sections/health-shots/2021/04/26/989962041/why-black-and-latino-people-still-lag-on-covid-vaccines-and-how-to-fix-it
11. Kaufman E. Lawmakers ask Biden to issue waiver to make COVID-19 vaccination mandatory of members of the military. Updated March 24, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/03/24/politics/congress-letter-military-vaccine/index.html
1. Garmone J. Secretary of Defense Addresses Vaccine Hesitancy in the Military. Published February 25, 2021. Accessed May 26, 2021. https://www.defense.gov/Explore/News/Article/Article/2516511/secretary-of-defense-addresses-vaccine-hesitancy-in-military/
2. National Academies of Sciences, Engineering, and Medicine. Framework for Equitable Allocation of COVID-19 Vaccine . The National Academies of Science; 2020:188. doi:10.17226/25917
3. Liebermann O. US military sees 55% jump in COVID-19 vaccinations over last month. Published May 20, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/05/20/politics/us-military-covid-vaccinations/index.html
4. Kime P. Almost one-third of us troops are refusing COVID-19 vaccines, officials Say. Published February 17, 2021. Accessed May 26, 2021. https://www.military.com/daily-news/2021/02/17/almost-one-third-of-us-troops-are-refusing-covid-vaccines-officials-say.html
5. Elbeshbishi S. Nearly 40% of Marines decline COVID-19 vaccine, prompting some Democrats to urge Biden to set mandate for the military. USA Today. April 10, 2021. Accessed May 26, 2021. https://www.usatoday.com/story/news/politics/2021/04/10/covid-vaccine-nearly-forty-percent-us-marines-decline/7173918002/
6. Lang MA, Stahlman S, Wells NY, et al. Disparities in COVID-19 vaccine initiation and completion among active component service members and health care personnel, 11 December 2020-12 March 2021. MSMR. 2021;28(4):2-9.
7. Webb Hooper M, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA . 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598
8. Kum D. Fueled by a history of mistreatment, Black Americans distrust the new COVID-19 vaccines. TIME. December 8, 2020. Accessed May 26, 2021.https://time.com/5925074/black-americans-covid-19-vaccine-distrust/
9. Bajaj SS, Stanford FC. Beyond Tuskegee - Vaccine Distrust and Everyday Racism. N Engl J Med. 2021;384(5):e12. doi:10.1056/NEJMpv2035827
10. Feldman N. Why Black and Latino people still lag on COVID-19 vaccines-and how to fix it. NPR. April 26, 2021. Accessed May 26, 2021. https://www.npr.org/sections/health-shots/2021/04/26/989962041/why-black-and-latino-people-still-lag-on-covid-vaccines-and-how-to-fix-it
11. Kaufman E. Lawmakers ask Biden to issue waiver to make COVID-19 vaccination mandatory of members of the military. Updated March 24, 2021. Accessed May 26, 2021. https://www.cnn.com/2021/03/24/politics/congress-letter-military-vaccine/index.html
COVID-19 Vaccine Reactions in Dermatology: “Filling” in the Gaps
As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.1 Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.
Cutaneous Vaccine Reactions and Facial Fillers
As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.2 The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.4
Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.5 A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.6 The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.7
After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.9 The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.9
The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.3
Counseling Patients and Reducing Risks
As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.3
Managing Vaccine Reactions
If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,9 but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.
If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.2 In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.
Final Thoughts
As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.
- Ritchie H, Ortiz-Ospina E, Beltekian D, et al. Coronavirus (COVID-19) vaccinations. Our World in Data website. Accessed May 10, 2021. https://ourworldindata.org/covid-vaccinations
- McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases [published online April 7, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.092
- Rice SM, Ferree SD, Mesinkovska NA, et al. The art of prevention: COVID-19 vaccine preparedness for the dermatologist. Int J Womens Dermatol. 2021;7:209-212. doi:10.1016/j.ijwd.2021.01.007
- Rice SM, Siegel JA, Libby T, et al. Zooming into cosmetic procedures during the COVID-19 pandemic: the provider’s perspective. Int J Womens Dermatol. 2021;7:213-216.
- FDA Briefing Document: Moderna COVID-19 Vaccine. US Department of Health and Human Services; 2020. Accessed May 11, 2021. https://www.fda.gov/media/144434/download
- Moderna’s COVID-19 vaccine may cause swelling, inflammation in those with facial fillers. American Society of Plastic Surgeons website. Published December 27, 2020. Accessed May 11, 2021. http://www.plasticsurgery.org/for-medical-professionals/publications/psn-extra/news/modernas-covid19-vaccine-may-cause-swelling-inflammation-in-those-with-facial-fillers
- Munavalli GG, Guthridge R, Knutsen-Larson S, et al. COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment [published online February 9, 2021]. Arch Dermatol Res. doi:10.1007/s00403-021-02190-6
- Schlessinger J. Update on COVID-19 vaccines and dermal fillers. Practical Dermatol. February 2021:46-47. Accessed May 10, 2021. https://practicaldermatology.com/articles/2021-feb/update-on-covid-19-vaccines-and-dermal-fillers/pdf
- Munavalli GG, Knutsen-Larson S, Lupo MP, et al. Oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following COVID-19 vaccination—a model for inhibition of angiotensin II-induced cutaneous inflammation. JAAD Case Rep. 2021;10:63-68. doi:10.1016/j.jdcr.2021.02.018
As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.1 Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.
Cutaneous Vaccine Reactions and Facial Fillers
As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.2 The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.4
Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.5 A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.6 The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.7
After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.9 The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.9
The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.3
Counseling Patients and Reducing Risks
As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.3
Managing Vaccine Reactions
If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,9 but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.
If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.2 In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.
Final Thoughts
As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.
As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.1 Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.
Cutaneous Vaccine Reactions and Facial Fillers
As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.2 The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.4
Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.5 A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.6 The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.7
After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.9 The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.9
The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.3
Counseling Patients and Reducing Risks
As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.3
Managing Vaccine Reactions
If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,9 but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.
If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.2 In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.
Final Thoughts
As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.
- Ritchie H, Ortiz-Ospina E, Beltekian D, et al. Coronavirus (COVID-19) vaccinations. Our World in Data website. Accessed May 10, 2021. https://ourworldindata.org/covid-vaccinations
- McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases [published online April 7, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.092
- Rice SM, Ferree SD, Mesinkovska NA, et al. The art of prevention: COVID-19 vaccine preparedness for the dermatologist. Int J Womens Dermatol. 2021;7:209-212. doi:10.1016/j.ijwd.2021.01.007
- Rice SM, Siegel JA, Libby T, et al. Zooming into cosmetic procedures during the COVID-19 pandemic: the provider’s perspective. Int J Womens Dermatol. 2021;7:213-216.
- FDA Briefing Document: Moderna COVID-19 Vaccine. US Department of Health and Human Services; 2020. Accessed May 11, 2021. https://www.fda.gov/media/144434/download
- Moderna’s COVID-19 vaccine may cause swelling, inflammation in those with facial fillers. American Society of Plastic Surgeons website. Published December 27, 2020. Accessed May 11, 2021. http://www.plasticsurgery.org/for-medical-professionals/publications/psn-extra/news/modernas-covid19-vaccine-may-cause-swelling-inflammation-in-those-with-facial-fillers
- Munavalli GG, Guthridge R, Knutsen-Larson S, et al. COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment [published online February 9, 2021]. Arch Dermatol Res. doi:10.1007/s00403-021-02190-6
- Schlessinger J. Update on COVID-19 vaccines and dermal fillers. Practical Dermatol. February 2021:46-47. Accessed May 10, 2021. https://practicaldermatology.com/articles/2021-feb/update-on-covid-19-vaccines-and-dermal-fillers/pdf
- Munavalli GG, Knutsen-Larson S, Lupo MP, et al. Oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following COVID-19 vaccination—a model for inhibition of angiotensin II-induced cutaneous inflammation. JAAD Case Rep. 2021;10:63-68. doi:10.1016/j.jdcr.2021.02.018
- Ritchie H, Ortiz-Ospina E, Beltekian D, et al. Coronavirus (COVID-19) vaccinations. Our World in Data website. Accessed May 10, 2021. https://ourworldindata.org/covid-vaccinations
- McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases [published online April 7, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.092
- Rice SM, Ferree SD, Mesinkovska NA, et al. The art of prevention: COVID-19 vaccine preparedness for the dermatologist. Int J Womens Dermatol. 2021;7:209-212. doi:10.1016/j.ijwd.2021.01.007
- Rice SM, Siegel JA, Libby T, et al. Zooming into cosmetic procedures during the COVID-19 pandemic: the provider’s perspective. Int J Womens Dermatol. 2021;7:213-216.
- FDA Briefing Document: Moderna COVID-19 Vaccine. US Department of Health and Human Services; 2020. Accessed May 11, 2021. https://www.fda.gov/media/144434/download
- Moderna’s COVID-19 vaccine may cause swelling, inflammation in those with facial fillers. American Society of Plastic Surgeons website. Published December 27, 2020. Accessed May 11, 2021. http://www.plasticsurgery.org/for-medical-professionals/publications/psn-extra/news/modernas-covid19-vaccine-may-cause-swelling-inflammation-in-those-with-facial-fillers
- Munavalli GG, Guthridge R, Knutsen-Larson S, et al. COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment [published online February 9, 2021]. Arch Dermatol Res. doi:10.1007/s00403-021-02190-6
- Schlessinger J. Update on COVID-19 vaccines and dermal fillers. Practical Dermatol. February 2021:46-47. Accessed May 10, 2021. https://practicaldermatology.com/articles/2021-feb/update-on-covid-19-vaccines-and-dermal-fillers/pdf
- Munavalli GG, Knutsen-Larson S, Lupo MP, et al. Oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following COVID-19 vaccination—a model for inhibition of angiotensin II-induced cutaneous inflammation. JAAD Case Rep. 2021;10:63-68. doi:10.1016/j.jdcr.2021.02.018
Not your ordinary neuropathy
She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?
A. Vitamin B12 deficiency
B. Diabetic neuropathy
C. Insulin neuritis
D. Charcot-Marie-Tooth disease
The most likely cause
In this case, certainly considering vitamin B12 deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B12 levels, and the American Diabetes Association has advised that regular monitoring of vitamin B12 levels should be done on patients who are on long-term metformin.1
Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
Research on TIN
Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.2 All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.
Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.3
A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.
A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.
Siddique and colleagues reported on three cases with very different clinical presentations of TIN.4 One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.
Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.2
Pearl
Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.
2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.
3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.
4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.
She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?
A. Vitamin B12 deficiency
B. Diabetic neuropathy
C. Insulin neuritis
D. Charcot-Marie-Tooth disease
The most likely cause
In this case, certainly considering vitamin B12 deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B12 levels, and the American Diabetes Association has advised that regular monitoring of vitamin B12 levels should be done on patients who are on long-term metformin.1
Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
Research on TIN
Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.2 All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.
Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.3
A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.
A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.
Siddique and colleagues reported on three cases with very different clinical presentations of TIN.4 One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.
Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.2
Pearl
Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.
2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.
3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.
4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.
She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?
A. Vitamin B12 deficiency
B. Diabetic neuropathy
C. Insulin neuritis
D. Charcot-Marie-Tooth disease
The most likely cause
In this case, certainly considering vitamin B12 deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B12 levels, and the American Diabetes Association has advised that regular monitoring of vitamin B12 levels should be done on patients who are on long-term metformin.1
Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
Research on TIN
Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.2 All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.
Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.3
A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.
A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.
Siddique and colleagues reported on three cases with very different clinical presentations of TIN.4 One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.
Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.2
Pearl
Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.
2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.
3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.
4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.