CASE

A 51-year-old man presents to your office to discuss lung cancer screening. He has a history of hypertension and prediabetes. His father died of lung cancer 5 years ago, at age 77. The patient stopped smoking soon thereafter; prior to that, he smoked 1 pack of cigarettes per day for 20 years. He wants to know if he should be screened for lung cancer.

The relative lack of symptoms during the early stages of lung cancer frequently results in a delayed diagnosis. This, and the speed at which the disease progresses, underscores the need for an effective screening modality. More than half of people with lung cancer die within 1 year of diagnosis.¹ Excluding skin cancer, lung cancer is the second most commonly diagnosed cancer, and more people die of lung cancer than of colon, breast, and prostate cancers combined.² In 2022, it was estimated that there would be 236,740 new cases of lung cancer and 130,180 deaths from lung cancer.^1,2 The average age at diagnosis is 70 years.²

Screening modalities: Only 1 has demonstrated mortality benefit

In 1968, Wilson and Junger³ outlined the characteristics of the ideal screening test for the World Health Organization: it should limit risk to the patient, be sensitive for detecting the disease early in its course, limit false-positive results, be acceptable to the patient, and be inexpensive to the health system.³ For decades, several screening modalities for lung cancer were trialed to fit the above guidance, but many of them fell short of the most important outcome: the impact on mortality.

Sputum cytology. The use of sputum cytology, either in combination with or without chest radiography, is not recommended. Several randomized controlled trials (RCTs) have failed to demonstrate improved lung cancer detection or mortality reduction in patients screened with this modality.⁴

Chest radiography (CXR). Several studies have assessed the efficacy of CXR as a screening modality. The best known was the Prostate, Lung, Colon, Ovarian (PLCO) Trial.⁵ This multicenter RCT enrolled more than 154,000 participants, half of whom received CXR at baseline and then annually for 3 years; the other half continued usual care (no screening). After 13 years of follow-up, there were no significant differences in lung cancer detection or mortality rates between the 2 groups.⁵

Low-dose computed tomography (LDCT). Several major medical societies recommend LDCT to screen high-risk individuals for lung cancer (TABLE 1^6-10). Results from 2 major RCTs have guided these recommendations.

At this time, low-dose computed tomography is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality.

The National Lung Screening Trial (NLST) was a multicenter RCT comparing 2 screening tests for lung cancer.¹¹ Approximately 54,000 high-risk participants were enrolled between 2002 and 2004 and were randomized to receive annual screening with either LDCT or single-view CXR. The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the LDCT group vs the CXR group.¹² This equates to 3 fewer deaths for every 1000 people screened with LDCT vs CXR. There was also a 6% reduction in all-cause mortality noted in the LDCT vs the CXR group.¹²

Continue to: The NELSON trial...

The NELSON trial, conducted between 2005 and 2015, studied more than 15,000 current or former smokers ages 50 to 74 years and compared LDCT screening at various intervals to no screening.¹³ After 10 years, lung cancer–related mortality was reduced by 24% (or 1 less death per 1000 person-years) in men who were screened vs their unscreened counterparts.¹³ In contrast to the NLST, in the NELSON trial, no significant difference in all-cause mortality was observed. Subgroup analysis of the relatively small population of women included in the NELSON trial suggested a 33% reduction in 10-year mortality; however, the difference was nonsignificant between the screened and unscreened groups.¹³

Each of these landmark studies had characteristics that could limit the results' generalizability to the US population. In the NELSON trial, more than 80% of the study participants were male. In both trials, there was significant underrepresentation of Black, Asian, Hispanic, and other non-White people.^12,13 Furthermore, participants in these studies were of higher socioeconomic status than the general US screening-eligible population.

At this time, LDCT is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality, in the populations that were studied. Based on the NLST, the number needed to screen (NNS) with LDCT to prevent 1 lung cancer–related death is 308. The NNS to prevent 1 death from any cause is 219.⁶

Updated evidence has led to a consensus on screening criteria

Many national societies endorse annual screening with LDCT in high-risk individuals (TABLE 1^6-10). Risk assessment for the purpose of lung cancer screening includes a detailed review of smoking history and age. The risk of lung cancer increases with advancing age and with cumulative quantity and duration of smoking, but decreases with increasing time since quitting. Therefore, a detailed smoking history should include total number of pack-years, current smoking status, and, if applicable, when smoking cessation occurred.

In 2021, the US Preventive Services Task Force (USPSTF) updated their 2013 lung cancer screening recommendations, expanding the screening age range and lowering the smoking history threshold for triggering initiation of screening.⁶ The impetus for the update was emerging evidence from systematic reviews, RCTs, and the Cancer Intervention and Surveillance Modeling Network ­(CISNET) that could help to determine the optimal age for screening and identify high-risk groups. For example, the NELSON trial, combined with results from CISNET modeling data, showed an empirical benefit for screening those ages 50 to 55 years.⁶

Continue to: As a result...

As a result, the USPSTF now recommends annual lung cancer screening with LDCT for any adult ages 50 to 80 years who has a 20-pack-year smoking history and currently smokes or has quit within the past 15 years.⁶ Screening should be discontinued once a person has not smoked for 15 years, develops a health problem that substantially limits life expectancy, or is not willing to have curative lung surgery.⁶

Expanding the screening eligibility may also address racial and gender disparities in health care. Black people and women who smoke have a higher risk for lung cancer at a lower intensity of smoking.⁶

Following the USPSTF update, the American College of Chest Physicians and the Centers for Medicare and Medicaid Services published updated guidance that aligns with USPSTF’s recommendations to lower the age and pack-year qualifications for initiating screening.^7,10 The American Cancer Society is currently reviewing its 2018 guidelines on lung cancer screening.¹⁴TABLE 1^6-10 summarizes the guidance on lung cancer screening from these medical societies.

Effective screening could save lives (and money)

A smoker’s risk for lung cancer is 20 times higher than that of a nonsmoker^15,16; 55% of lung cancer deaths in women and 70% in men are attributed to smoking.¹⁷ Once diagnosed with lung cancer, more than 50% of people will die within 1 year.¹ This underpins the need for a lung cancer screening modality that reduces mortality. Large RCTs, including the NLST and NELSONtrials, have shown that screening high-risk individuals with LDCT can significantly reduce lung cancer–related death when compared to no screening or screening with CXR alone.^11,13

There is controversy surrounding the cost benefit of implementing a nationwide lung cancer screening program. However, recent use of microsimulation models has shown LDCT to be a cost-effective strategy, with an average cost of $81,000 per quality-adjusted life-year, which is below the threshold of $100,000 to be considered cost effective.¹⁸ Expanding the upper age limit for screening leads to a greater reduction in mortality but increases treatment costs and overdiagnosis rates, and overall does not improve quality-adjusted life-years.¹⁸

Continue to: Potential harms

Potential harms: False-positives and related complications

Screening for lung cancer is not without its risks. Harms from screening typically result from false-positive test results leading to over­diagnosis, anxiety and distress, unnecessary invasive tests or procedures, and increased costs.¹⁹TABLE 2^6,19-23 lists specific complications from lung cancer screening with LDCT.

The false-positive rate is not trivial. For every 1000 patients screened, 250 people will have a positive LDCT finding but will not have lung cancer.¹⁹ Furthermore, about 1 in every 2000 individuals who screen positive, but who do not have lung cancer, die as a result of complications from the ensuing work-up.⁶

Annual LDCT screening increases the risk of radiation-induced cancer by approximately 0.05% over 10 years.²¹ The absolute risk is generally low but not insignificant. However, the mortality benefits previously outlined are significantly more robust in both absolute and relative terms vs the 10-year risk of radiation-induced cancer.

The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the lowdose computed tomography group vs the chest x-ray group.

Lastly, it is important to note that the NELSON trial and NLST included a limited number of LDCT scans. Current guidelines for lung cancer screening with LDCT, including those from the USPSTF, recommend screening annually. We do not know the cumulative harm of annual LDCT over a 20- or 30-year period for those who would qualify (ie, current smokers).

If you screen, you must be able to act on the results

Effective screening programs should extend beyond the LDCT scan itself. The studies that have shown a benefit of LDCT were done at large academic centers that had the appropriate radiologic, pathologic, and surgical infrastructure to interpret and act on results and offer further diagnostic or treatment procedures.

Continue to: Prior to screening...

Prior to screening for lung cancer with LDCT, documentation of shared decision-making between the patient and the clinician is necessary.⁷ This discussion should include the potential benefits and harms of screening, potential results and likelihood of follow-up diagnostic testing, the false-positive rate of LDCT lung cancer screening, and cumulative radiation exposure. In addition, screening should be considered only if the patient is willing to be screened annually, is willing to pursue follow-up scans and procedures (including lung biopsy) if deemed necessary, and does not have comorbid conditions that significantly limit life expectancy.

Smoking cessation: The most important change to make

Smoking cessation is the single most important risk-modifying behavior to reduce one’s chance of developing lung cancer. At age 40, smokers have a 2-fold increase in all-cause mortality compared to age-matched nonsmokers. This rises to a 3-fold increase by the age of 70.¹⁶

Smoking cessation reduces the risk of lung cancer by 20% after 5 years, 30% to 50% after 10 years, and up to 70% after 15 years.²⁴ In its guidelines, the American Thoracic Society recommends varenicline (Chantix) for all smokers to assist with smoking cessation.²⁵

CASE

This 51-year-old patient with at least a 20-pack-year history of smoking should be commended for giving up smoking. Based on the USPSTF recommendations, he should be screened annually with LDCT for the next 10 years.

Screening to save more lives

The results of 2 large multicenter RCTs have led to the recent recommendation for lung cancer screening of high-risk adults with the use of LDCT. Screening with LDCT has been shown to reduce disease-related mortality and likely be cost effective in the long term.

Screening with LDCT should be part of a multidisciplinary system that has the infrastructure not only to perform the screening, but also to diagnose and appropriately follow up and treat patients whose results are concerning. The risk of false-positive results leading to increased anxiety, overdiagnosis, and unnecessary procedures points to the importance of proper patient selection, counseling, and shared decision-making. Smoking cessation remains the most important disease-modifying behavior one can make to reduce their risk for lung cancer.

CORRESPONDENCE
Carlton J. Covey, MD, 101 Bodin Circle, David Grant Medical Center, Travis Air Force Base, Fairfield, CA, 94545; [email protected]

CASE

A 51-year-old man presents to your office to discuss lung cancer screening. He has a history of hypertension and prediabetes. His father died of lung cancer 5 years ago, at age 77. The patient stopped smoking soon thereafter; prior to that, he smoked 1 pack of cigarettes per day for 20 years. He wants to know if he should be screened for lung cancer.

The relative lack of symptoms during the early stages of lung cancer frequently results in a delayed diagnosis. This, and the speed at which the disease progresses, underscores the need for an effective screening modality. More than half of people with lung cancer die within 1 year of diagnosis.¹ Excluding skin cancer, lung cancer is the second most commonly diagnosed cancer, and more people die of lung cancer than of colon, breast, and prostate cancers combined.² In 2022, it was estimated that there would be 236,740 new cases of lung cancer and 130,180 deaths from lung cancer.^1,2 The average age at diagnosis is 70 years.²

Screening modalities: Only 1 has demonstrated mortality benefit

In 1968, Wilson and Junger³ outlined the characteristics of the ideal screening test for the World Health Organization: it should limit risk to the patient, be sensitive for detecting the disease early in its course, limit false-positive results, be acceptable to the patient, and be inexpensive to the health system.³ For decades, several screening modalities for lung cancer were trialed to fit the above guidance, but many of them fell short of the most important outcome: the impact on mortality.

Sputum cytology. The use of sputum cytology, either in combination with or without chest radiography, is not recommended. Several randomized controlled trials (RCTs) have failed to demonstrate improved lung cancer detection or mortality reduction in patients screened with this modality.⁴

Chest radiography (CXR). Several studies have assessed the efficacy of CXR as a screening modality. The best known was the Prostate, Lung, Colon, Ovarian (PLCO) Trial.⁵ This multicenter RCT enrolled more than 154,000 participants, half of whom received CXR at baseline and then annually for 3 years; the other half continued usual care (no screening). After 13 years of follow-up, there were no significant differences in lung cancer detection or mortality rates between the 2 groups.⁵

Low-dose computed tomography (LDCT). Several major medical societies recommend LDCT to screen high-risk individuals for lung cancer (TABLE 1^6-10). Results from 2 major RCTs have guided these recommendations.

At this time, low-dose computed tomography is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality.

The National Lung Screening Trial (NLST) was a multicenter RCT comparing 2 screening tests for lung cancer.¹¹ Approximately 54,000 high-risk participants were enrolled between 2002 and 2004 and were randomized to receive annual screening with either LDCT or single-view CXR. The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the LDCT group vs the CXR group.¹² This equates to 3 fewer deaths for every 1000 people screened with LDCT vs CXR. There was also a 6% reduction in all-cause mortality noted in the LDCT vs the CXR group.¹²

Continue to: The NELSON trial...

The NELSON trial, conducted between 2005 and 2015, studied more than 15,000 current or former smokers ages 50 to 74 years and compared LDCT screening at various intervals to no screening.¹³ After 10 years, lung cancer–related mortality was reduced by 24% (or 1 less death per 1000 person-years) in men who were screened vs their unscreened counterparts.¹³ In contrast to the NLST, in the NELSON trial, no significant difference in all-cause mortality was observed. Subgroup analysis of the relatively small population of women included in the NELSON trial suggested a 33% reduction in 10-year mortality; however, the difference was nonsignificant between the screened and unscreened groups.¹³

Each of these landmark studies had characteristics that could limit the results' generalizability to the US population. In the NELSON trial, more than 80% of the study participants were male. In both trials, there was significant underrepresentation of Black, Asian, Hispanic, and other non-White people.^12,13 Furthermore, participants in these studies were of higher socioeconomic status than the general US screening-eligible population.

At this time, LDCT is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality, in the populations that were studied. Based on the NLST, the number needed to screen (NNS) with LDCT to prevent 1 lung cancer–related death is 308. The NNS to prevent 1 death from any cause is 219.⁶

Updated evidence has led to a consensus on screening criteria

Many national societies endorse annual screening with LDCT in high-risk individuals (TABLE 1^6-10). Risk assessment for the purpose of lung cancer screening includes a detailed review of smoking history and age. The risk of lung cancer increases with advancing age and with cumulative quantity and duration of smoking, but decreases with increasing time since quitting. Therefore, a detailed smoking history should include total number of pack-years, current smoking status, and, if applicable, when smoking cessation occurred.

In 2021, the US Preventive Services Task Force (USPSTF) updated their 2013 lung cancer screening recommendations, expanding the screening age range and lowering the smoking history threshold for triggering initiation of screening.⁶ The impetus for the update was emerging evidence from systematic reviews, RCTs, and the Cancer Intervention and Surveillance Modeling Network ­(CISNET) that could help to determine the optimal age for screening and identify high-risk groups. For example, the NELSON trial, combined with results from CISNET modeling data, showed an empirical benefit for screening those ages 50 to 55 years.⁶

Continue to: As a result...

As a result, the USPSTF now recommends annual lung cancer screening with LDCT for any adult ages 50 to 80 years who has a 20-pack-year smoking history and currently smokes or has quit within the past 15 years.⁶ Screening should be discontinued once a person has not smoked for 15 years, develops a health problem that substantially limits life expectancy, or is not willing to have curative lung surgery.⁶

Expanding the screening eligibility may also address racial and gender disparities in health care. Black people and women who smoke have a higher risk for lung cancer at a lower intensity of smoking.⁶

Following the USPSTF update, the American College of Chest Physicians and the Centers for Medicare and Medicaid Services published updated guidance that aligns with USPSTF’s recommendations to lower the age and pack-year qualifications for initiating screening.^7,10 The American Cancer Society is currently reviewing its 2018 guidelines on lung cancer screening.¹⁴TABLE 1^6-10 summarizes the guidance on lung cancer screening from these medical societies.

Effective screening could save lives (and money)

A smoker’s risk for lung cancer is 20 times higher than that of a nonsmoker^15,16; 55% of lung cancer deaths in women and 70% in men are attributed to smoking.¹⁷ Once diagnosed with lung cancer, more than 50% of people will die within 1 year.¹ This underpins the need for a lung cancer screening modality that reduces mortality. Large RCTs, including the NLST and NELSONtrials, have shown that screening high-risk individuals with LDCT can significantly reduce lung cancer–related death when compared to no screening or screening with CXR alone.^11,13

There is controversy surrounding the cost benefit of implementing a nationwide lung cancer screening program. However, recent use of microsimulation models has shown LDCT to be a cost-effective strategy, with an average cost of $81,000 per quality-adjusted life-year, which is below the threshold of $100,000 to be considered cost effective.¹⁸ Expanding the upper age limit for screening leads to a greater reduction in mortality but increases treatment costs and overdiagnosis rates, and overall does not improve quality-adjusted life-years.¹⁸

Continue to: Potential harms

Potential harms: False-positives and related complications

Screening for lung cancer is not without its risks. Harms from screening typically result from false-positive test results leading to over­diagnosis, anxiety and distress, unnecessary invasive tests or procedures, and increased costs.¹⁹TABLE 2^6,19-23 lists specific complications from lung cancer screening with LDCT.

The false-positive rate is not trivial. For every 1000 patients screened, 250 people will have a positive LDCT finding but will not have lung cancer.¹⁹ Furthermore, about 1 in every 2000 individuals who screen positive, but who do not have lung cancer, die as a result of complications from the ensuing work-up.⁶

Annual LDCT screening increases the risk of radiation-induced cancer by approximately 0.05% over 10 years.²¹ The absolute risk is generally low but not insignificant. However, the mortality benefits previously outlined are significantly more robust in both absolute and relative terms vs the 10-year risk of radiation-induced cancer.

The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the lowdose computed tomography group vs the chest x-ray group.

Lastly, it is important to note that the NELSON trial and NLST included a limited number of LDCT scans. Current guidelines for lung cancer screening with LDCT, including those from the USPSTF, recommend screening annually. We do not know the cumulative harm of annual LDCT over a 20- or 30-year period for those who would qualify (ie, current smokers).

If you screen, you must be able to act on the results

Effective screening programs should extend beyond the LDCT scan itself. The studies that have shown a benefit of LDCT were done at large academic centers that had the appropriate radiologic, pathologic, and surgical infrastructure to interpret and act on results and offer further diagnostic or treatment procedures.

Continue to: Prior to screening...

Prior to screening for lung cancer with LDCT, documentation of shared decision-making between the patient and the clinician is necessary.⁷ This discussion should include the potential benefits and harms of screening, potential results and likelihood of follow-up diagnostic testing, the false-positive rate of LDCT lung cancer screening, and cumulative radiation exposure. In addition, screening should be considered only if the patient is willing to be screened annually, is willing to pursue follow-up scans and procedures (including lung biopsy) if deemed necessary, and does not have comorbid conditions that significantly limit life expectancy.

Smoking cessation: The most important change to make

Smoking cessation is the single most important risk-modifying behavior to reduce one’s chance of developing lung cancer. At age 40, smokers have a 2-fold increase in all-cause mortality compared to age-matched nonsmokers. This rises to a 3-fold increase by the age of 70.¹⁶

Smoking cessation reduces the risk of lung cancer by 20% after 5 years, 30% to 50% after 10 years, and up to 70% after 15 years.²⁴ In its guidelines, the American Thoracic Society recommends varenicline (Chantix) for all smokers to assist with smoking cessation.²⁵

CASE

This 51-year-old patient with at least a 20-pack-year history of smoking should be commended for giving up smoking. Based on the USPSTF recommendations, he should be screened annually with LDCT for the next 10 years.

Screening to save more lives

The results of 2 large multicenter RCTs have led to the recent recommendation for lung cancer screening of high-risk adults with the use of LDCT. Screening with LDCT has been shown to reduce disease-related mortality and likely be cost effective in the long term.

Screening with LDCT should be part of a multidisciplinary system that has the infrastructure not only to perform the screening, but also to diagnose and appropriately follow up and treat patients whose results are concerning. The risk of false-positive results leading to increased anxiety, overdiagnosis, and unnecessary procedures points to the importance of proper patient selection, counseling, and shared decision-making. Smoking cessation remains the most important disease-modifying behavior one can make to reduce their risk for lung cancer.

CORRESPONDENCE
Carlton J. Covey, MD, 101 Bodin Circle, David Grant Medical Center, Travis Air Force Base, Fairfield, CA, 94545; [email protected]

CASE

A 51-year-old man presents to your office to discuss lung cancer screening. He has a history of hypertension and prediabetes. His father died of lung cancer 5 years ago, at age 77. The patient stopped smoking soon thereafter; prior to that, he smoked 1 pack of cigarettes per day for 20 years. He wants to know if he should be screened for lung cancer.

The relative lack of symptoms during the early stages of lung cancer frequently results in a delayed diagnosis. This, and the speed at which the disease progresses, underscores the need for an effective screening modality. More than half of people with lung cancer die within 1 year of diagnosis.¹ Excluding skin cancer, lung cancer is the second most commonly diagnosed cancer, and more people die of lung cancer than of colon, breast, and prostate cancers combined.² In 2022, it was estimated that there would be 236,740 new cases of lung cancer and 130,180 deaths from lung cancer.^1,2 The average age at diagnosis is 70 years.²

Screening modalities: Only 1 has demonstrated mortality benefit

In 1968, Wilson and Junger³ outlined the characteristics of the ideal screening test for the World Health Organization: it should limit risk to the patient, be sensitive for detecting the disease early in its course, limit false-positive results, be acceptable to the patient, and be inexpensive to the health system.³ For decades, several screening modalities for lung cancer were trialed to fit the above guidance, but many of them fell short of the most important outcome: the impact on mortality.

Sputum cytology. The use of sputum cytology, either in combination with or without chest radiography, is not recommended. Several randomized controlled trials (RCTs) have failed to demonstrate improved lung cancer detection or mortality reduction in patients screened with this modality.⁴

Chest radiography (CXR). Several studies have assessed the efficacy of CXR as a screening modality. The best known was the Prostate, Lung, Colon, Ovarian (PLCO) Trial.⁵ This multicenter RCT enrolled more than 154,000 participants, half of whom received CXR at baseline and then annually for 3 years; the other half continued usual care (no screening). After 13 years of follow-up, there were no significant differences in lung cancer detection or mortality rates between the 2 groups.⁵

Low-dose computed tomography (LDCT). Several major medical societies recommend LDCT to screen high-risk individuals for lung cancer (TABLE 1^6-10). Results from 2 major RCTs have guided these recommendations.

At this time, low-dose computed tomography is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality.

The National Lung Screening Trial (NLST) was a multicenter RCT comparing 2 screening tests for lung cancer.¹¹ Approximately 54,000 high-risk participants were enrolled between 2002 and 2004 and were randomized to receive annual screening with either LDCT or single-view CXR. The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the LDCT group vs the CXR group.¹² This equates to 3 fewer deaths for every 1000 people screened with LDCT vs CXR. There was also a 6% reduction in all-cause mortality noted in the LDCT vs the CXR group.¹²

Continue to: The NELSON trial...

The NELSON trial, conducted between 2005 and 2015, studied more than 15,000 current or former smokers ages 50 to 74 years and compared LDCT screening at various intervals to no screening.¹³ After 10 years, lung cancer–related mortality was reduced by 24% (or 1 less death per 1000 person-years) in men who were screened vs their unscreened counterparts.¹³ In contrast to the NLST, in the NELSON trial, no significant difference in all-cause mortality was observed. Subgroup analysis of the relatively small population of women included in the NELSON trial suggested a 33% reduction in 10-year mortality; however, the difference was nonsignificant between the screened and unscreened groups.¹³

Each of these landmark studies had characteristics that could limit the results' generalizability to the US population. In the NELSON trial, more than 80% of the study participants were male. In both trials, there was significant underrepresentation of Black, Asian, Hispanic, and other non-White people.^12,13 Furthermore, participants in these studies were of higher socioeconomic status than the general US screening-eligible population.

At this time, LDCT is the only lung cancer screening modality that has shown benefit for both disease-related and all-cause mortality, in the populations that were studied. Based on the NLST, the number needed to screen (NNS) with LDCT to prevent 1 lung cancer–related death is 308. The NNS to prevent 1 death from any cause is 219.⁶

Updated evidence has led to a consensus on screening criteria

Many national societies endorse annual screening with LDCT in high-risk individuals (TABLE 1^6-10). Risk assessment for the purpose of lung cancer screening includes a detailed review of smoking history and age. The risk of lung cancer increases with advancing age and with cumulative quantity and duration of smoking, but decreases with increasing time since quitting. Therefore, a detailed smoking history should include total number of pack-years, current smoking status, and, if applicable, when smoking cessation occurred.

In 2021, the US Preventive Services Task Force (USPSTF) updated their 2013 lung cancer screening recommendations, expanding the screening age range and lowering the smoking history threshold for triggering initiation of screening.⁶ The impetus for the update was emerging evidence from systematic reviews, RCTs, and the Cancer Intervention and Surveillance Modeling Network ­(CISNET) that could help to determine the optimal age for screening and identify high-risk groups. For example, the NELSON trial, combined with results from CISNET modeling data, showed an empirical benefit for screening those ages 50 to 55 years.⁶

Continue to: As a result...

As a result, the USPSTF now recommends annual lung cancer screening with LDCT for any adult ages 50 to 80 years who has a 20-pack-year smoking history and currently smokes or has quit within the past 15 years.⁶ Screening should be discontinued once a person has not smoked for 15 years, develops a health problem that substantially limits life expectancy, or is not willing to have curative lung surgery.⁶

Expanding the screening eligibility may also address racial and gender disparities in health care. Black people and women who smoke have a higher risk for lung cancer at a lower intensity of smoking.⁶

Following the USPSTF update, the American College of Chest Physicians and the Centers for Medicare and Medicaid Services published updated guidance that aligns with USPSTF’s recommendations to lower the age and pack-year qualifications for initiating screening.^7,10 The American Cancer Society is currently reviewing its 2018 guidelines on lung cancer screening.¹⁴TABLE 1^6-10 summarizes the guidance on lung cancer screening from these medical societies.

Effective screening could save lives (and money)

A smoker’s risk for lung cancer is 20 times higher than that of a nonsmoker^15,16; 55% of lung cancer deaths in women and 70% in men are attributed to smoking.¹⁷ Once diagnosed with lung cancer, more than 50% of people will die within 1 year.¹ This underpins the need for a lung cancer screening modality that reduces mortality. Large RCTs, including the NLST and NELSONtrials, have shown that screening high-risk individuals with LDCT can significantly reduce lung cancer–related death when compared to no screening or screening with CXR alone.^11,13

There is controversy surrounding the cost benefit of implementing a nationwide lung cancer screening program. However, recent use of microsimulation models has shown LDCT to be a cost-effective strategy, with an average cost of $81,000 per quality-adjusted life-year, which is below the threshold of $100,000 to be considered cost effective.¹⁸ Expanding the upper age limit for screening leads to a greater reduction in mortality but increases treatment costs and overdiagnosis rates, and overall does not improve quality-adjusted life-years.¹⁸

Continue to: Potential harms

Potential harms: False-positives and related complications

Screening for lung cancer is not without its risks. Harms from screening typically result from false-positive test results leading to over­diagnosis, anxiety and distress, unnecessary invasive tests or procedures, and increased costs.¹⁹TABLE 2^6,19-23 lists specific complications from lung cancer screening with LDCT.

The false-positive rate is not trivial. For every 1000 patients screened, 250 people will have a positive LDCT finding but will not have lung cancer.¹⁹ Furthermore, about 1 in every 2000 individuals who screen positive, but who do not have lung cancer, die as a result of complications from the ensuing work-up.⁶

Annual LDCT screening increases the risk of radiation-induced cancer by approximately 0.05% over 10 years.²¹ The absolute risk is generally low but not insignificant. However, the mortality benefits previously outlined are significantly more robust in both absolute and relative terms vs the 10-year risk of radiation-induced cancer.

The trial was discontinued prematurely when investigators noted a 20% reduction in lung cancer mortality in the lowdose computed tomography group vs the chest x-ray group.

Lastly, it is important to note that the NELSON trial and NLST included a limited number of LDCT scans. Current guidelines for lung cancer screening with LDCT, including those from the USPSTF, recommend screening annually. We do not know the cumulative harm of annual LDCT over a 20- or 30-year period for those who would qualify (ie, current smokers).

If you screen, you must be able to act on the results

Effective screening programs should extend beyond the LDCT scan itself. The studies that have shown a benefit of LDCT were done at large academic centers that had the appropriate radiologic, pathologic, and surgical infrastructure to interpret and act on results and offer further diagnostic or treatment procedures.

Continue to: Prior to screening...

Prior to screening for lung cancer with LDCT, documentation of shared decision-making between the patient and the clinician is necessary.⁷ This discussion should include the potential benefits and harms of screening, potential results and likelihood of follow-up diagnostic testing, the false-positive rate of LDCT lung cancer screening, and cumulative radiation exposure. In addition, screening should be considered only if the patient is willing to be screened annually, is willing to pursue follow-up scans and procedures (including lung biopsy) if deemed necessary, and does not have comorbid conditions that significantly limit life expectancy.

Smoking cessation: The most important change to make

Smoking cessation is the single most important risk-modifying behavior to reduce one’s chance of developing lung cancer. At age 40, smokers have a 2-fold increase in all-cause mortality compared to age-matched nonsmokers. This rises to a 3-fold increase by the age of 70.¹⁶

Smoking cessation reduces the risk of lung cancer by 20% after 5 years, 30% to 50% after 10 years, and up to 70% after 15 years.²⁴ In its guidelines, the American Thoracic Society recommends varenicline (Chantix) for all smokers to assist with smoking cessation.²⁵

CASE

This 51-year-old patient with at least a 20-pack-year history of smoking should be commended for giving up smoking. Based on the USPSTF recommendations, he should be screened annually with LDCT for the next 10 years.

Screening to save more lives

The results of 2 large multicenter RCTs have led to the recent recommendation for lung cancer screening of high-risk adults with the use of LDCT. Screening with LDCT has been shown to reduce disease-related mortality and likely be cost effective in the long term.

Screening with LDCT should be part of a multidisciplinary system that has the infrastructure not only to perform the screening, but also to diagnose and appropriately follow up and treat patients whose results are concerning. The risk of false-positive results leading to increased anxiety, overdiagnosis, and unnecessary procedures points to the importance of proper patient selection, counseling, and shared decision-making. Smoking cessation remains the most important disease-modifying behavior one can make to reduce their risk for lung cancer.

CORRESPONDENCE
Carlton J. Covey, MD, 101 Bodin Circle, David Grant Medical Center, Travis Air Force Base, Fairfield, CA, 94545; [email protected]

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Undiagnosed atrial fibrillation (AFib) was significantly more common among adults with obstructive sleep apnea (OSA), compared with controls, based on data from 303 individuals.

OSA has become a common chronic disease, and cardiovascular diseases including AFib also are known independent risk factors associated with OSA, Anna Hojager, MD, of Zealand University Hospital, Roskilde, Denmark, and colleagues wrote. Previous studies have shown a significant increase in AFib risk in OSA patients with severe disease, but the prevalence of undiagnosed AFib in OSA patients has not been explored.

In a study published in Sleep Medicine, the researchers enrolled 238 adults with severe OSA (based on apnea-hypopnea index of 15 or higher) and 65 with mild or no OSA (based on an AHI of less than 15). The mean AHI across all participants was 34.2, and ranged from 0.2 to 115.8.

Participants underwent heart rhythm monitoring using a home system or standard ECG for 7 days; they were instructed to carry the device at all times except when showering or sweating heavily. The primary outcome was the detection of AFib, defined as at least one period of 30 seconds or longer with an irregular heart rhythm but without detectable evidence of another diagnosis. Sleep was assessed for one night using a portable sleep monitoring device. All participants were examined at baseline and measured for blood pressure, body mass index, waist-to-hip ratio, and ECG.

Overall, AFib occurred in 21 patients with moderate to severe OSA and 1 patient with mild/no OSA (8.8% vs. 1.5%, P = .045). The majority of patients across both groups had hypertension (66%) and dyslipidemia (77.6%), but the severe OSA group was more likely to be dysregulated and to have unknown prediabetes. Participants who were deemed candidates for anticoagulation therapy were referred for additional treatment. None of the 22 total patients with AFib had heart failure with reduced ejection fraction, and 68.2% had normal ejection fraction and ventricle function.

The researchers noted that no guidelines currently exist for systematic opportunistic screening for comorbidities in OSA patients, although the American Academy of Sleep Medicine recommends patient education as part of a multidisciplinary chronic disease management strategy. The high prevalence of AFib in OSA patients, as seen in the current study, “might warrant a recommendation of screening for paroxysmal [AFib] and could be valuable in the management of modifiable cardiovascular risk factors in patients with OSA,” they wrote.

The study findings were limited by several factors including the observational design and absence of polysomnography to assess OSA, the researchers noted. However, the study has the highest known prevalence of silent AFib in patients with moderate to severe OSA, and supports the value of screening and management for known comorbidities of OSA.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Dr. Neil Skolnik. Today we’re going to talk about the consensus report by the American Diabetes Association and the European Association for the Study of Diabetes on the management of hyperglycemia.

A lot has changed in this consensus statement. It covers a lot of ground. We’re going to focus today on pharmacologic management.

After lifestyle modifications, metformin is no longer the go-to drug for every patient in the management of hyperglycemia. It is recommended that we assess each patient’s personal characteristics in deciding what medication to prescribe. For patients at high cardiorenal risk, refer to the left side of the algorithm and to the right side for all other patients.

American Diabetes Association

• Very high efficacy for glucose lowering: dulaglutide at a high dose, semaglutide, tirzepatide, insulin, or combination injectable agents (GLP-1 receptor agonist/insulin combinations).
• High glucose-lowering efficacy: a GLP-1 receptor agonist not already mentioned, metformin, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones.
• Intermediate glucose lowering efficacy: dipeptidyl peptidase 4 (DPP-4) inhibitors.

Weight management. For weight management, lifestyle modification (diet and exercise) is important. If lifestyle modification alone is insufficient, consider either a medication that specifically helps with weight management or metabolic surgery.

We particularly want to focus on weight management in patients who have complications from obesity. What would those complications be? Sleep apnea, hip or knee pain from arthritis, back pain – that is, biomechanical complications of obesity or nonalcoholic fatty liver disease. Medications for weight loss are listed by degree of efficacy:

• Very high efficacy for weight loss: semaglutide, tirzepatide.
• High efficacy for weight loss: dulaglutide and liraglutide.
• Intermediate for weight loss: GLP-1 receptor agonist (not listed above), SGLT-2 inhibitor.
• Neutral for weight loss: DPP-4 inhibitors and metformin.

Where does insulin fit in? If patients present with a very high A1c, if they are on other medications and their A1c is still not to goal, or if they are catabolic and losing weight because of their diabetes, then insulin has an important place in management.

These are incredibly important guidelines that provide a clear algorithm for a personalized approach to diabetes management.
 

Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He reported conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. A version of this article first appeared on Medscape.com.

The respiratory illness RSV causes 1 in 50 deaths in children under age 5, mostly in low-income and middle-income countries, a new study says.

But RSV – formally known as respiratory syncytial virus – is also a problem in high-income nations. In those countries, 1 in 56 otherwise healthy babies are hospitalized with RSV during their first year of life, said the study, which was published in the Lancet Respiratory Medicine.

Researchers looked at the health records of 9,154 infants born between July 1, 2017, and July 31, 2020, who were treated at health centers across Europe. Previous studies have concentrated on babies with preexisting conditions, but this one looked at otherwise healthy children, researchers said.

“This is the lowest-risk baby who is being hospitalized for this, so really, numbers are really much higher than I think some people would have guessed,” said study coauthor Louis Bont, MD, a professor of pediatric infectious diseases at Wilhelmina Children’s Hospital at University Medical Center Utrecht in the Netherlands, according to CNN. He is also chairman of the ReSViNET foundation, which aims to reduce RSV infection globally.

The study said more than 97% of deaths from RSV occur in low-income and middle-income countries. The study concluded that “maternal vaccination and passive [immunization] could have a profound impact on the RSV burden.”

In developed nations, children who get RSV usually survive because they have access to ventilators and other health care equipment. Still, just being treated for RSV can have long-range negative effects on a child’s health, Kristina Deeter, MD, chair of pediatrics at the University of Nevada, Reno, told CNN.

“Whether that is just traumatic psychosocial, emotional issues after hospitalization or even having more vulnerable lungs – you can develop asthma later on, for instance, if you’ve had a really severe infection at a young age – it can damage your lungs permanently,” she said of the study. “It’s still an important virus in our world and something that we really focus on.”

The Lancet study was published days after the CDC warned public health officials that respiratory viruses, including RSV, are surging among children across the country.

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

The respiratory illness RSV causes 1 in 50 deaths in children under age 5, mostly in low-income and middle-income countries, a new study says.

But RSV – formally known as respiratory syncytial virus – is also a problem in high-income nations. In those countries, 1 in 56 otherwise healthy babies are hospitalized with RSV during their first year of life, said the study, which was published in the Lancet Respiratory Medicine.

Researchers looked at the health records of 9,154 infants born between July 1, 2017, and July 31, 2020, who were treated at health centers across Europe. Previous studies have concentrated on babies with preexisting conditions, but this one looked at otherwise healthy children, researchers said.

“This is the lowest-risk baby who is being hospitalized for this, so really, numbers are really much higher than I think some people would have guessed,” said study coauthor Louis Bont, MD, a professor of pediatric infectious diseases at Wilhelmina Children’s Hospital at University Medical Center Utrecht in the Netherlands, according to CNN. He is also chairman of the ReSViNET foundation, which aims to reduce RSV infection globally.

The study said more than 97% of deaths from RSV occur in low-income and middle-income countries. The study concluded that “maternal vaccination and passive [immunization] could have a profound impact on the RSV burden.”

In developed nations, children who get RSV usually survive because they have access to ventilators and other health care equipment. Still, just being treated for RSV can have long-range negative effects on a child’s health, Kristina Deeter, MD, chair of pediatrics at the University of Nevada, Reno, told CNN.

“Whether that is just traumatic psychosocial, emotional issues after hospitalization or even having more vulnerable lungs – you can develop asthma later on, for instance, if you’ve had a really severe infection at a young age – it can damage your lungs permanently,” she said of the study. “It’s still an important virus in our world and something that we really focus on.”

The Lancet study was published days after the CDC warned public health officials that respiratory viruses, including RSV, are surging among children across the country.

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

The respiratory illness RSV causes 1 in 50 deaths in children under age 5, mostly in low-income and middle-income countries, a new study says.

But RSV – formally known as respiratory syncytial virus – is also a problem in high-income nations. In those countries, 1 in 56 otherwise healthy babies are hospitalized with RSV during their first year of life, said the study, which was published in the Lancet Respiratory Medicine.

Researchers looked at the health records of 9,154 infants born between July 1, 2017, and July 31, 2020, who were treated at health centers across Europe. Previous studies have concentrated on babies with preexisting conditions, but this one looked at otherwise healthy children, researchers said.

“This is the lowest-risk baby who is being hospitalized for this, so really, numbers are really much higher than I think some people would have guessed,” said study coauthor Louis Bont, MD, a professor of pediatric infectious diseases at Wilhelmina Children’s Hospital at University Medical Center Utrecht in the Netherlands, according to CNN. He is also chairman of the ReSViNET foundation, which aims to reduce RSV infection globally.

The study said more than 97% of deaths from RSV occur in low-income and middle-income countries. The study concluded that “maternal vaccination and passive [immunization] could have a profound impact on the RSV burden.”

In developed nations, children who get RSV usually survive because they have access to ventilators and other health care equipment. Still, just being treated for RSV can have long-range negative effects on a child’s health, Kristina Deeter, MD, chair of pediatrics at the University of Nevada, Reno, told CNN.

“Whether that is just traumatic psychosocial, emotional issues after hospitalization or even having more vulnerable lungs – you can develop asthma later on, for instance, if you’ve had a really severe infection at a young age – it can damage your lungs permanently,” she said of the study. “It’s still an important virus in our world and something that we really focus on.”

The Lancet study was published days after the CDC warned public health officials that respiratory viruses, including RSV, are surging among children across the country.

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

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

Mindfulness-based stress reduction (MBSR) is as effective at reducing anxiety as the antidepressant escitalopram, a first-line pharmaceutical treatment, new research shows.

“I would encourage clinicians to list meditation training as one possible treatment option for patients who are diagnosed with anxiety disorders. Doctors should feel comfortable recommending in-person, group-based meditation classes,” study investigator Elizabeth A. Hoge, MD, director, Anxiety Disorders Research Program, Georgetown University Medical Center, Washington, told this news organization.

The findings were published online  in JAMA Psychiatry.
 

Screening recommended

Anxiety disorders, including generalized anxiety, social anxiety, panic disorder, and agoraphobia, are the most common type of mental disorder, affecting an estimated 301 million people worldwide. Owing to their high prevalence, the United States Preventive Services Task Force recommends screening for anxiety disorders.

Effective treatments for anxiety disorders include medications and cognitive-behavioral therapy. However, not all patients have access to these interventions, respond to them, or are comfortable seeking care in a psychiatric setting.

Mindfulness meditation, which has risen in popularity in recent years, may help people experiencing intrusive, anxious thoughts. “By practicing mindfulness meditation, people learn not to be overwhelmed by those thoughts,” said Dr. Hoge.

The study included 276 adult patients with an anxiety disorder, mostly generalized anxiety or social anxiety. The mean age of the study population was 33 years; 75% were women, 59% were White, 15% were Black, and 20% were Asian.

Researchers randomly assigned 136 patients to receive MBSR and 140 to receive the selective serotonin reuptake inhibitor escitalopram, a first-line medication for treating anxiety disorders.

The MBSR intervention included a weekly 2.5-hour class and a day-long weekend class. Participants also completed daily 45-minute guided meditation sessions at home. They learned mindfulness meditation exercises, including breath awareness, body scanning, and mindful movement.

Those in the escitalopram group initially received 10 mg of the oral drug daily. The dose was increased to 20 mg daily at week 2 if well tolerated.

The primary outcome was the score on the Clinical Global Impression of Severity (CGI-S) scale for anxiety, assessed by clinicians blinded to treatment allocation. This instrument measures overall symptom severity on a scale from 1 (not at all ill) to 7 (most extremely ill) and can be used to assess different types of anxiety disorders, said Dr. Hoge.

Among the 208 participants who completed the study, the baseline mean CGI-S score was 4.44 for MBSR and 4.51 for escitalopram. At week 8, on the CGI-S scale, the MBSR group’s score improved by a mean of 1.35 points, and the escitalopram group’s score improved by 1.43 points (difference of –0.07; 95% CI, –0.38 to 0.23; P = .65).

The lower end of the confidence interval (–0.38) was smaller than the prespecified noninferiority margin of –0.495, indicating noninferiority of MBSR, compared with escitalopram.
 

Remarkable results

“What was remarkable was that the medication worked great, like it always does, but the meditation also worked great; we saw about a 30% drop in symptoms for both groups,” said Dr. Hoge. “That helps us know that meditation, and in particular mindfulness meditation, could be useful as a first-line treatment for patients with anxiety disorders.”

The patient-reported outcome of the Overall Anxiety Severity and Impairment Scale also showed no significant group differences. “It’s important to have the self-reports, because that gives us two ways to look at the information,” said Dr. Hoge.

Anecdotally, participants noted that the meditation helped with their personal relationships and with being “kinder to themselves,” said Dr. Hoge. “In meditation, there’s an implicit teaching to be accepting and nonjudgmental towards your own thoughts, and that teaches people to be more self-compassionate.”

Just over 78% of patients in the escitalopram group had at least one treatment-related adverse event (AE), which included sleep disturbances, nausea, fatigue, and headache, compared with 15.4% in the MBSR group.

The most common AE in the meditation group was anxiety, which is “counterintuitive” but represents “a momentary anxiety,” said Dr. Hoge. “People who are meditating have feelings come up that maybe they didn’t pay attention to before. This gives them an opportunity to process through those emotions.”

Fatigue was the next most common AE for meditators, which “makes sense,” since they’re putting away their phones and not being stimulated, said Dr. Hoge.

MBSR was delivered in person, which limits extrapolation to mindfulness apps or programs delivered over the internet. Dr. Hoge believes apps would likely be less effective because they don’t have the face-to-face component, instructors available for consultation, or fellow participants contributing group support.

But online classes might work if “the exact same class,” including all its components, is moved online, she said.

MBSR is available in all major U.S. cities, doesn’t require finding a therapist, and is available outside a mental health environment – for example, at yoga centers and some places of employment. Anyone can learn MBSR, although it takes time and commitment, said Dr. Hoge.
 

A time-tested intervention

Commenting on the study, psychiatrist Gregory Scott Brown, MD, affiliate faculty, University of Texas Dell Medical School, and author of “The Self-Healing Mind: An Essential Five-Step Practice for Overcoming Anxiety and Depression and Revitalizing Your Life,” said the results aren’t surprising inasmuch as mindfulness, including spirituality, breath work, and meditation, is a “time-tested and evidence-based” intervention.

“I’m encouraged by the fact studies like this are now being conducted and there’s more evidence that supports these mindfulness-based interventions, so they can start to make their way into standard-of-care treatments.” he said.

He noted that mindfulness can produce “long-term, sustainable improvements” and that the 45-minute daily home exercise included in the study “is not a huge time commitment when you talk about benefits you can potentially glean from incorporating that time.”

Because most study participants were women and “men are anxious too,” Dr. Brown said he would like to see the study replicated “with a more diverse pool of participants.”

The study was supported by the Patient-Centered Outcomes Research Institute. Dr. Hoge and Dr. Brown have reported no relevant financial relationships.

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

Trauma-related dissociation consists of several subtypes, with unique brain signatures depending on type of dissociative disorders, new research suggests.

Results from a neuroimaging study showed that different dissociative symptoms were linked to hyperconnectivity within several key regions of the brain, including the central executive, default, and salience networks as well as decreased connectivity of the central executive and salience networks with other brain areas.

Depersonalization/derealization showed a different brain signature than partially dissociated intrusions, and participants with posttraumatic stress disorder showed a different brain signature, compared with those who had dissociative identity disorder (DID).

“Dissociation is a complex, subjective set of symptoms that are largely experienced internally and, contrary to media portrayal, are not usually overtly observable,” lead author Lauren Lebois, PhD, director of the Dissociative Disorders and Trauma Research Program, McLean Hospital, Belmont, Mass., and assistant professor of psychiatry at Harvard Medical School, Boston, told this news organization.

“However, we have shown that you can objectively measure dissociation and link it to robust brain signatures. We hope these results will encourage clinicians to screen for dissociation and approach reports of these experiences seriously, empathetically, and with awareness that they can be treated effectively,” Dr. Lebois said.

The findings were published online  in Neuropsychopharmacology.
 

Detachment, discontinuity

Pathological dissociation is “the experience of detachment from or discontinuity in one’s internal experience, sense of self, or surroundings” and is common in the aftermath of trauma, the investigators write.

Previous research into trauma-related pathological dissociation suggests it encompasses a range of experiences or “subtypes,” some of which frequently occur in PTSD and DID.

“Depersonalization and derealization involve feelings of detachment or disconnection from one’s sense of self, body, and environment,” the current researchers write. “Individuals report feeling like their body or surroundings are unreal or like they are in a movie.”

Dissociation also includes “experiences of self-alteration common in DID, in which people lose a sense of agency and ownership over their thoughts, emotions, actions, and body [and] experience some thoughts, emotions, etc. as partially dissociated intrusions,” Dr. Lebois said.

She added that dissociative symptoms are “common and disabling.” And dissociation and severe dissociative disorders such as DID “remain at best underappreciated and, at worst, frequently go undiagnosed or misdiagnosed,” with a high cost of stigmatization and misunderstanding preventing individuals from accessing effective treatment.

In addition, “given that DID disproportionately affects women, gender disparity is an important issue in this context,” Dr. Lebois noted.

Her team was motivated to conduct the study “to learn more about how different types of dissociation manifest in brain activity and to help combat the stigma around dissociation and DID.”
 

Filling the gap

The investigators drew on the “Triple Network” model of psychopathology, which “offers an integrative framework based in systems neuroscience for understanding cognitive and affective dysfunction across psychiatric conditions,” they write.

This model “implicates altered intrinsic organization and interactions between three large-scale brain networks across disorders,” they add.

The brain networks included in the study were the right-lateralized central executive network (rCEN), with the lateral frontoparietal brain region; the medial temporal subnetwork of the default network (tDN), with the medial frontoparietal brain region; and the cingulo-opercular subnetwork (cSN), with the midcingulo-insular brain region.

Previous neuroimaging research into dissociative disorders has implicated altered connectivity in these regions. However, although previous studies covered dissociation subtypes, they did not directly compare these subtypes. This study was designed to fill that gap, the investigators note.

They assessed 91 women with and without a history of childhood trauma, current PTSD, and with varying degrees of dissociation.

This included 19 with conventional PTSD (mean age, 33.4 years), 18 with PTSD dissociative subtype (mean age, 29.5 years), 26 with DID (mean age, 37.4 years), and 28 who acted as the healthy control group (mean age, 32 years).

Participants completed several scales regarding symptoms of PTSD, dissociation, and childhood trauma. They also underwent functional magnetic resonance imaging. Covariates included age, childhood maltreatment, and PTSD severity.
 

Connectivity alterations

Results showed the rCEN was “most impacted” by pathological dissociation, with 39 clusters linked to connectivity alterations.

Ten clusters within tDN exhibited within-network hyperconnectivity related to dissociation but only of the depersonalization/derealization subtype.

Eight clusters within cSN were linked to dissociation – specifically, within-network hyperconnectivity and decreased connectivity between regions in rCEN with cSN, with “no significant unique contributions of dissociation subtypes,” the researchers report.

“Depersonalization and derealization symptoms were associated with increased communication between a brain network involved in reasoning, attention, inhibition, and working memory and a brain region implicated in out-of-body experiences. This may, in part, contribute to depersonalization/derealization feelings of detachment, strangeness or unreality experienced with your body and surroundings,” Dr. Lebois said.

“In contrast, partially dissociated intrusion symptoms central to DID were linked to increased communication between a brain network involved in autobiographical memory and your sense of self and a brain network involved in reasoning, attention, inhibition, and working memory,” she added.

She noted that this matches how patients with DID describe their mental experiences: as sometimes feeling as if they lost a sense of ownership over their own thoughts and feelings, which can “intrude into their mental landscape.”

In the future, Dr. Lebois hopes that “we may be able to monitor dissociative brain signatures during psychotherapy to help assess recovery or relapse, or we could target brain activity directly with neurofeedback or neuromodulatory techniques as a dissociation treatment in and of itself.”
 

A first step?

Commenting on the study, Richard Loewenstein, MD, adjunct professor, department of psychiatry, University of Maryland School of Medicine, Baltimore, called the paper a “first step in more sophisticated studies of pathological dissociation using cutting-edge concepts of brain connectivity, methodology based on naturalistic, dimensional symptoms categories, and innovative statistical methods.”

Dr. Loewenstein, who was not involved with the current study, added that there is an “oversimplified conflation of hallucinations and other symptoms of dissociation with psychosis.” So studies may “incorrectly relate phenomena such as racism-based trauma to psychosis, rather than pathological dissociation and racism-based PTSD,” he said.

He noted that the implications are “profound, as pathological dissociation is not treatable with antipsychotic medications and requires treatment with psychotherapy specifically targeting symptoms of pathological dissociation.”

The study was funded by the Julia Kasparian Fund for Neuroscience Research and the National Institute of Mental Health. Dr. Lebois reported unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation, grant support from the NIMH and the Julia Kasparian Fund for Neuroscience Research, and spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals unrelated to the present work. The other investigators’ disclosures are listed in the original paper. Dr. Loewenstein has disclosed no relevant financial relationships.

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

Trauma-related dissociation consists of several subtypes, with unique brain signatures depending on type of dissociative disorders, new research suggests.

Results from a neuroimaging study showed that different dissociative symptoms were linked to hyperconnectivity within several key regions of the brain, including the central executive, default, and salience networks as well as decreased connectivity of the central executive and salience networks with other brain areas.

Depersonalization/derealization showed a different brain signature than partially dissociated intrusions, and participants with posttraumatic stress disorder showed a different brain signature, compared with those who had dissociative identity disorder (DID).

“Dissociation is a complex, subjective set of symptoms that are largely experienced internally and, contrary to media portrayal, are not usually overtly observable,” lead author Lauren Lebois, PhD, director of the Dissociative Disorders and Trauma Research Program, McLean Hospital, Belmont, Mass., and assistant professor of psychiatry at Harvard Medical School, Boston, told this news organization.

“However, we have shown that you can objectively measure dissociation and link it to robust brain signatures. We hope these results will encourage clinicians to screen for dissociation and approach reports of these experiences seriously, empathetically, and with awareness that they can be treated effectively,” Dr. Lebois said.

The findings were published online  in Neuropsychopharmacology.
 

Detachment, discontinuity

Pathological dissociation is “the experience of detachment from or discontinuity in one’s internal experience, sense of self, or surroundings” and is common in the aftermath of trauma, the investigators write.

Previous research into trauma-related pathological dissociation suggests it encompasses a range of experiences or “subtypes,” some of which frequently occur in PTSD and DID.

“Depersonalization and derealization involve feelings of detachment or disconnection from one’s sense of self, body, and environment,” the current researchers write. “Individuals report feeling like their body or surroundings are unreal or like they are in a movie.”

Dissociation also includes “experiences of self-alteration common in DID, in which people lose a sense of agency and ownership over their thoughts, emotions, actions, and body [and] experience some thoughts, emotions, etc. as partially dissociated intrusions,” Dr. Lebois said.

She added that dissociative symptoms are “common and disabling.” And dissociation and severe dissociative disorders such as DID “remain at best underappreciated and, at worst, frequently go undiagnosed or misdiagnosed,” with a high cost of stigmatization and misunderstanding preventing individuals from accessing effective treatment.

In addition, “given that DID disproportionately affects women, gender disparity is an important issue in this context,” Dr. Lebois noted.

Her team was motivated to conduct the study “to learn more about how different types of dissociation manifest in brain activity and to help combat the stigma around dissociation and DID.”
 

Filling the gap

The investigators drew on the “Triple Network” model of psychopathology, which “offers an integrative framework based in systems neuroscience for understanding cognitive and affective dysfunction across psychiatric conditions,” they write.

This model “implicates altered intrinsic organization and interactions between three large-scale brain networks across disorders,” they add.

The brain networks included in the study were the right-lateralized central executive network (rCEN), with the lateral frontoparietal brain region; the medial temporal subnetwork of the default network (tDN), with the medial frontoparietal brain region; and the cingulo-opercular subnetwork (cSN), with the midcingulo-insular brain region.

Previous neuroimaging research into dissociative disorders has implicated altered connectivity in these regions. However, although previous studies covered dissociation subtypes, they did not directly compare these subtypes. This study was designed to fill that gap, the investigators note.

They assessed 91 women with and without a history of childhood trauma, current PTSD, and with varying degrees of dissociation.

This included 19 with conventional PTSD (mean age, 33.4 years), 18 with PTSD dissociative subtype (mean age, 29.5 years), 26 with DID (mean age, 37.4 years), and 28 who acted as the healthy control group (mean age, 32 years).

Participants completed several scales regarding symptoms of PTSD, dissociation, and childhood trauma. They also underwent functional magnetic resonance imaging. Covariates included age, childhood maltreatment, and PTSD severity.
 

Connectivity alterations

Results showed the rCEN was “most impacted” by pathological dissociation, with 39 clusters linked to connectivity alterations.

Ten clusters within tDN exhibited within-network hyperconnectivity related to dissociation but only of the depersonalization/derealization subtype.

Eight clusters within cSN were linked to dissociation – specifically, within-network hyperconnectivity and decreased connectivity between regions in rCEN with cSN, with “no significant unique contributions of dissociation subtypes,” the researchers report.

“Depersonalization and derealization symptoms were associated with increased communication between a brain network involved in reasoning, attention, inhibition, and working memory and a brain region implicated in out-of-body experiences. This may, in part, contribute to depersonalization/derealization feelings of detachment, strangeness or unreality experienced with your body and surroundings,” Dr. Lebois said.

“In contrast, partially dissociated intrusion symptoms central to DID were linked to increased communication between a brain network involved in autobiographical memory and your sense of self and a brain network involved in reasoning, attention, inhibition, and working memory,” she added.

She noted that this matches how patients with DID describe their mental experiences: as sometimes feeling as if they lost a sense of ownership over their own thoughts and feelings, which can “intrude into their mental landscape.”

In the future, Dr. Lebois hopes that “we may be able to monitor dissociative brain signatures during psychotherapy to help assess recovery or relapse, or we could target brain activity directly with neurofeedback or neuromodulatory techniques as a dissociation treatment in and of itself.”
 

A first step?

Commenting on the study, Richard Loewenstein, MD, adjunct professor, department of psychiatry, University of Maryland School of Medicine, Baltimore, called the paper a “first step in more sophisticated studies of pathological dissociation using cutting-edge concepts of brain connectivity, methodology based on naturalistic, dimensional symptoms categories, and innovative statistical methods.”

Dr. Loewenstein, who was not involved with the current study, added that there is an “oversimplified conflation of hallucinations and other symptoms of dissociation with psychosis.” So studies may “incorrectly relate phenomena such as racism-based trauma to psychosis, rather than pathological dissociation and racism-based PTSD,” he said.

He noted that the implications are “profound, as pathological dissociation is not treatable with antipsychotic medications and requires treatment with psychotherapy specifically targeting symptoms of pathological dissociation.”

The study was funded by the Julia Kasparian Fund for Neuroscience Research and the National Institute of Mental Health. Dr. Lebois reported unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation, grant support from the NIMH and the Julia Kasparian Fund for Neuroscience Research, and spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals unrelated to the present work. The other investigators’ disclosures are listed in the original paper. Dr. Loewenstein has disclosed no relevant financial relationships.

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

Trauma-related dissociation consists of several subtypes, with unique brain signatures depending on type of dissociative disorders, new research suggests.

Results from a neuroimaging study showed that different dissociative symptoms were linked to hyperconnectivity within several key regions of the brain, including the central executive, default, and salience networks as well as decreased connectivity of the central executive and salience networks with other brain areas.

Depersonalization/derealization showed a different brain signature than partially dissociated intrusions, and participants with posttraumatic stress disorder showed a different brain signature, compared with those who had dissociative identity disorder (DID).

“Dissociation is a complex, subjective set of symptoms that are largely experienced internally and, contrary to media portrayal, are not usually overtly observable,” lead author Lauren Lebois, PhD, director of the Dissociative Disorders and Trauma Research Program, McLean Hospital, Belmont, Mass., and assistant professor of psychiatry at Harvard Medical School, Boston, told this news organization.

“However, we have shown that you can objectively measure dissociation and link it to robust brain signatures. We hope these results will encourage clinicians to screen for dissociation and approach reports of these experiences seriously, empathetically, and with awareness that they can be treated effectively,” Dr. Lebois said.

The findings were published online  in Neuropsychopharmacology.
 

Detachment, discontinuity

Pathological dissociation is “the experience of detachment from or discontinuity in one’s internal experience, sense of self, or surroundings” and is common in the aftermath of trauma, the investigators write.

Previous research into trauma-related pathological dissociation suggests it encompasses a range of experiences or “subtypes,” some of which frequently occur in PTSD and DID.

“Depersonalization and derealization involve feelings of detachment or disconnection from one’s sense of self, body, and environment,” the current researchers write. “Individuals report feeling like their body or surroundings are unreal or like they are in a movie.”

Dissociation also includes “experiences of self-alteration common in DID, in which people lose a sense of agency and ownership over their thoughts, emotions, actions, and body [and] experience some thoughts, emotions, etc. as partially dissociated intrusions,” Dr. Lebois said.

She added that dissociative symptoms are “common and disabling.” And dissociation and severe dissociative disorders such as DID “remain at best underappreciated and, at worst, frequently go undiagnosed or misdiagnosed,” with a high cost of stigmatization and misunderstanding preventing individuals from accessing effective treatment.

In addition, “given that DID disproportionately affects women, gender disparity is an important issue in this context,” Dr. Lebois noted.

Her team was motivated to conduct the study “to learn more about how different types of dissociation manifest in brain activity and to help combat the stigma around dissociation and DID.”
 

Filling the gap

The investigators drew on the “Triple Network” model of psychopathology, which “offers an integrative framework based in systems neuroscience for understanding cognitive and affective dysfunction across psychiatric conditions,” they write.

This model “implicates altered intrinsic organization and interactions between three large-scale brain networks across disorders,” they add.

The brain networks included in the study were the right-lateralized central executive network (rCEN), with the lateral frontoparietal brain region; the medial temporal subnetwork of the default network (tDN), with the medial frontoparietal brain region; and the cingulo-opercular subnetwork (cSN), with the midcingulo-insular brain region.

Previous neuroimaging research into dissociative disorders has implicated altered connectivity in these regions. However, although previous studies covered dissociation subtypes, they did not directly compare these subtypes. This study was designed to fill that gap, the investigators note.

They assessed 91 women with and without a history of childhood trauma, current PTSD, and with varying degrees of dissociation.

This included 19 with conventional PTSD (mean age, 33.4 years), 18 with PTSD dissociative subtype (mean age, 29.5 years), 26 with DID (mean age, 37.4 years), and 28 who acted as the healthy control group (mean age, 32 years).

Participants completed several scales regarding symptoms of PTSD, dissociation, and childhood trauma. They also underwent functional magnetic resonance imaging. Covariates included age, childhood maltreatment, and PTSD severity.
 

Connectivity alterations

Results showed the rCEN was “most impacted” by pathological dissociation, with 39 clusters linked to connectivity alterations.

Ten clusters within tDN exhibited within-network hyperconnectivity related to dissociation but only of the depersonalization/derealization subtype.

Eight clusters within cSN were linked to dissociation – specifically, within-network hyperconnectivity and decreased connectivity between regions in rCEN with cSN, with “no significant unique contributions of dissociation subtypes,” the researchers report.

“Depersonalization and derealization symptoms were associated with increased communication between a brain network involved in reasoning, attention, inhibition, and working memory and a brain region implicated in out-of-body experiences. This may, in part, contribute to depersonalization/derealization feelings of detachment, strangeness or unreality experienced with your body and surroundings,” Dr. Lebois said.

“In contrast, partially dissociated intrusion symptoms central to DID were linked to increased communication between a brain network involved in autobiographical memory and your sense of self and a brain network involved in reasoning, attention, inhibition, and working memory,” she added.

She noted that this matches how patients with DID describe their mental experiences: as sometimes feeling as if they lost a sense of ownership over their own thoughts and feelings, which can “intrude into their mental landscape.”

In the future, Dr. Lebois hopes that “we may be able to monitor dissociative brain signatures during psychotherapy to help assess recovery or relapse, or we could target brain activity directly with neurofeedback or neuromodulatory techniques as a dissociation treatment in and of itself.”
 

A first step?

Commenting on the study, Richard Loewenstein, MD, adjunct professor, department of psychiatry, University of Maryland School of Medicine, Baltimore, called the paper a “first step in more sophisticated studies of pathological dissociation using cutting-edge concepts of brain connectivity, methodology based on naturalistic, dimensional symptoms categories, and innovative statistical methods.”

Dr. Loewenstein, who was not involved with the current study, added that there is an “oversimplified conflation of hallucinations and other symptoms of dissociation with psychosis.” So studies may “incorrectly relate phenomena such as racism-based trauma to psychosis, rather than pathological dissociation and racism-based PTSD,” he said.

He noted that the implications are “profound, as pathological dissociation is not treatable with antipsychotic medications and requires treatment with psychotherapy specifically targeting symptoms of pathological dissociation.”

The study was funded by the Julia Kasparian Fund for Neuroscience Research and the National Institute of Mental Health. Dr. Lebois reported unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation, grant support from the NIMH and the Julia Kasparian Fund for Neuroscience Research, and spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals unrelated to the present work. The other investigators’ disclosures are listed in the original paper. Dr. Loewenstein has disclosed no relevant financial relationships.

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

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

The terms Microtox, MicroBotox, Mesotox, and MesoBotox have been thrown around in the dermatology literature, clinical medicine, and the media, leaving patients confused about what they treat and physicians confused about what patients want when they mention one of these terms.

Let’s settle the nomenclature confusion. In this column, I define and outline suggested terminology based on studies and my 15 years of experience using neuromodulators. If any readers or colleagues disagree, please write to me and we can discuss the alternatives in a subsequent article; if you agree, please also write to me so we can collaboratively correct the discrepancies in the literature accordingly.

The term mesotherapy, originating from the Greek “mesos” referring to the early embryonic mesoderm, was identified in the 1950’s by Dr. Michel Pistor, a French physician who administered drugs intradermally. The term was defined as a minimally invasive technique by which drugs or bioactive substances are given in small quantities through dermal micropunctures. Drugs administered intradermally diffuse very slowly and therefore, stay in the tissue longer than those administered intramuscularly.

Thus, Mesotox is defined not by the concentration of the neuromodulator or location, but by the depth of injection in the superficial dermis. It can be delivered through individual injections or through a microneedling pen.

Microtox refers to the dilution of the neuromodulator at concentrations below the proposed dilution guidelines of the manufacturer: Less than 2.5 U per 0.1 mL for onabotulinumtoxinA (OBA), incobotulinumtoxinA (IBA), and prabotulinumtoxinA (PBA); and less than 10 U per 0.1 mL for abobotulinumtoxinA (ABO), This method allows for the injection of superficial cutaneous muscles softening the dynamic rhytids without complete paralysis.

Mesotox is widely used off label for facial lifting, reduction in skin laxity or crepiness, flushing of rosacea, acne, hyperhidrosis of the face, keloids, seborrhea, neck rejuvenation, contouring of the mandibular border, and scalp oiliness. Based on a review of articles using this technique, dilution methods were less than 2.5 U per 1 mL (OBA, IBA) and less than 10 U per 0.1 mL (ABO) depth of injection was the superficial to mid-dermis with injection points 0.5 cm to 1 cm apart.

In a study by Atwa and colleagues, 25 patients with mild facial skin laxity received intradermal Botox-A on one side and saline on the other. This split face study showed a highly significant difference with facial lifting on the treated side. Mesotox injection points vary based on the clinical indication and area being treated.

The treatment of dynamic muscles using standard neuromodulator dosing protocols include the treatment of the glabella, crow’s feet, forehead lines, masseter hypertrophy, bunny lines, gummy smile, perioral lines, mentalis hypertonia, platysmal bands, and marionette lines.

However, hyperdilute neuromodulators or Microtox can effectively be used alone or in combination with standard dosing for the following off-label uses. Used in combination with standard dosing of the forehead lines, I use Microtox in the lateral brow to soften the frontalis muscle without dropping the brow in patients with a low-set brow or lid laxity. I also use it for the jelly roll of the eyes and to open the aperture of the eyes. Along the nose, Microtox can also be used to treat a sagging nasal tip, decrease the width of the ala, and treat overactive facial muscles adjacent to the nose resulting in an overactive nasolabial fold.

Similarly, Microtox can be used to treat lateral smile lines and downward extensions of the crow’s feet. In all of the aforementioned treatment areas, I recommend approximately 0.5-1 U of toxin in each area divided at 1-cm intervals.Mesotox and Microtox are both highly effective strategies to treat the aging face. However, the nomenclature is not interchangeable. I propose that the term Mesotox be used only to articulate or define the superficial injection of a neuromodulator for the improvement of the skin that does not involve the injection into or paralysis of a cutaneous muscle (“tox” being used generically for all neuromodulators). I also propose that the term Microtox should be used to define the dilution of a neuromodulator beyond the manufacturer-recommended dilution protocols – used for the paralysis of a cutaneous muscle. In addition, I recommend that the terms MicroBotox and MesoBotox no longer be used. These procedures all have risks, and adverse events associated with Microtox and Mesotox are similar to those of any neuromodulator injection at FDA-recommended maximum doses, and dilution and storage protocols and proper injection techniques need to be followed. Expertise and training is crucial and treatment by a board-certified dermatologist or plastic surgeon is imperative.

 

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to her at [email protected]. Dr. Talakoub had no relevant disclosures.

References

Awaida CJ et al. Plast Reconstr Surg. 2018 Sep;142(3):640-9.

Calvani F et al. Plast Surg (Oakv). 2019 May;27(2):156-61.

Iranmanesh B et al. J Cosmet Dermatol. 2022 Oct;21(10):4160-70.

Kandhari R et al. J Cutan Aesthet Surg. 2022 Apr-Jun;15(2):101-7.

Lewandowski M et al. Molecules. 2022 May 13;27(10):3143.

Mammucari M et al. Eur Rev Med Pharmacol Sci. 2011 Jun;15(6):682-94.

Park KY et al. Ann Dermatol. 2018 Dec;30(6):688-93.

Pistor M. Chir Dent Fr. 1976;46:59-60.

Rho NK, Gil YC. Toxins (Basel). 2021 Nov 19;13(11):817.

Wu WTL. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):92S-100S.

Zhang H et al. Clin Cosmet Investig Dermatol. 2021 Apr 30;14:407-17.
 

The terms Microtox, MicroBotox, Mesotox, and MesoBotox have been thrown around in the dermatology literature, clinical medicine, and the media, leaving patients confused about what they treat and physicians confused about what patients want when they mention one of these terms.

Let’s settle the nomenclature confusion. In this column, I define and outline suggested terminology based on studies and my 15 years of experience using neuromodulators. If any readers or colleagues disagree, please write to me and we can discuss the alternatives in a subsequent article; if you agree, please also write to me so we can collaboratively correct the discrepancies in the literature accordingly.

The term mesotherapy, originating from the Greek “mesos” referring to the early embryonic mesoderm, was identified in the 1950’s by Dr. Michel Pistor, a French physician who administered drugs intradermally. The term was defined as a minimally invasive technique by which drugs or bioactive substances are given in small quantities through dermal micropunctures. Drugs administered intradermally diffuse very slowly and therefore, stay in the tissue longer than those administered intramuscularly.

Thus, Mesotox is defined not by the concentration of the neuromodulator or location, but by the depth of injection in the superficial dermis. It can be delivered through individual injections or through a microneedling pen.

Microtox refers to the dilution of the neuromodulator at concentrations below the proposed dilution guidelines of the manufacturer: Less than 2.5 U per 0.1 mL for onabotulinumtoxinA (OBA), incobotulinumtoxinA (IBA), and prabotulinumtoxinA (PBA); and less than 10 U per 0.1 mL for abobotulinumtoxinA (ABO), This method allows for the injection of superficial cutaneous muscles softening the dynamic rhytids without complete paralysis.

Mesotox is widely used off label for facial lifting, reduction in skin laxity or crepiness, flushing of rosacea, acne, hyperhidrosis of the face, keloids, seborrhea, neck rejuvenation, contouring of the mandibular border, and scalp oiliness. Based on a review of articles using this technique, dilution methods were less than 2.5 U per 1 mL (OBA, IBA) and less than 10 U per 0.1 mL (ABO) depth of injection was the superficial to mid-dermis with injection points 0.5 cm to 1 cm apart.

In a study by Atwa and colleagues, 25 patients with mild facial skin laxity received intradermal Botox-A on one side and saline on the other. This split face study showed a highly significant difference with facial lifting on the treated side. Mesotox injection points vary based on the clinical indication and area being treated.

The treatment of dynamic muscles using standard neuromodulator dosing protocols include the treatment of the glabella, crow’s feet, forehead lines, masseter hypertrophy, bunny lines, gummy smile, perioral lines, mentalis hypertonia, platysmal bands, and marionette lines.

However, hyperdilute neuromodulators or Microtox can effectively be used alone or in combination with standard dosing for the following off-label uses. Used in combination with standard dosing of the forehead lines, I use Microtox in the lateral brow to soften the frontalis muscle without dropping the brow in patients with a low-set brow or lid laxity. I also use it for the jelly roll of the eyes and to open the aperture of the eyes. Along the nose, Microtox can also be used to treat a sagging nasal tip, decrease the width of the ala, and treat overactive facial muscles adjacent to the nose resulting in an overactive nasolabial fold.

Similarly, Microtox can be used to treat lateral smile lines and downward extensions of the crow’s feet. In all of the aforementioned treatment areas, I recommend approximately 0.5-1 U of toxin in each area divided at 1-cm intervals.Mesotox and Microtox are both highly effective strategies to treat the aging face. However, the nomenclature is not interchangeable. I propose that the term Mesotox be used only to articulate or define the superficial injection of a neuromodulator for the improvement of the skin that does not involve the injection into or paralysis of a cutaneous muscle (“tox” being used generically for all neuromodulators). I also propose that the term Microtox should be used to define the dilution of a neuromodulator beyond the manufacturer-recommended dilution protocols – used for the paralysis of a cutaneous muscle. In addition, I recommend that the terms MicroBotox and MesoBotox no longer be used. These procedures all have risks, and adverse events associated with Microtox and Mesotox are similar to those of any neuromodulator injection at FDA-recommended maximum doses, and dilution and storage protocols and proper injection techniques need to be followed. Expertise and training is crucial and treatment by a board-certified dermatologist or plastic surgeon is imperative.

 

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to her at [email protected]. Dr. Talakoub had no relevant disclosures.

References

Awaida CJ et al. Plast Reconstr Surg. 2018 Sep;142(3):640-9.

Calvani F et al. Plast Surg (Oakv). 2019 May;27(2):156-61.

Iranmanesh B et al. J Cosmet Dermatol. 2022 Oct;21(10):4160-70.

Kandhari R et al. J Cutan Aesthet Surg. 2022 Apr-Jun;15(2):101-7.

Lewandowski M et al. Molecules. 2022 May 13;27(10):3143.

Mammucari M et al. Eur Rev Med Pharmacol Sci. 2011 Jun;15(6):682-94.

Park KY et al. Ann Dermatol. 2018 Dec;30(6):688-93.

Pistor M. Chir Dent Fr. 1976;46:59-60.

Rho NK, Gil YC. Toxins (Basel). 2021 Nov 19;13(11):817.

Wu WTL. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):92S-100S.

Zhang H et al. Clin Cosmet Investig Dermatol. 2021 Apr 30;14:407-17.
 

The terms Microtox, MicroBotox, Mesotox, and MesoBotox have been thrown around in the dermatology literature, clinical medicine, and the media, leaving patients confused about what they treat and physicians confused about what patients want when they mention one of these terms.

Let’s settle the nomenclature confusion. In this column, I define and outline suggested terminology based on studies and my 15 years of experience using neuromodulators. If any readers or colleagues disagree, please write to me and we can discuss the alternatives in a subsequent article; if you agree, please also write to me so we can collaboratively correct the discrepancies in the literature accordingly.

The term mesotherapy, originating from the Greek “mesos” referring to the early embryonic mesoderm, was identified in the 1950’s by Dr. Michel Pistor, a French physician who administered drugs intradermally. The term was defined as a minimally invasive technique by which drugs or bioactive substances are given in small quantities through dermal micropunctures. Drugs administered intradermally diffuse very slowly and therefore, stay in the tissue longer than those administered intramuscularly.

Thus, Mesotox is defined not by the concentration of the neuromodulator or location, but by the depth of injection in the superficial dermis. It can be delivered through individual injections or through a microneedling pen.

Microtox refers to the dilution of the neuromodulator at concentrations below the proposed dilution guidelines of the manufacturer: Less than 2.5 U per 0.1 mL for onabotulinumtoxinA (OBA), incobotulinumtoxinA (IBA), and prabotulinumtoxinA (PBA); and less than 10 U per 0.1 mL for abobotulinumtoxinA (ABO), This method allows for the injection of superficial cutaneous muscles softening the dynamic rhytids without complete paralysis.

Mesotox is widely used off label for facial lifting, reduction in skin laxity or crepiness, flushing of rosacea, acne, hyperhidrosis of the face, keloids, seborrhea, neck rejuvenation, contouring of the mandibular border, and scalp oiliness. Based on a review of articles using this technique, dilution methods were less than 2.5 U per 1 mL (OBA, IBA) and less than 10 U per 0.1 mL (ABO) depth of injection was the superficial to mid-dermis with injection points 0.5 cm to 1 cm apart.

In a study by Atwa and colleagues, 25 patients with mild facial skin laxity received intradermal Botox-A on one side and saline on the other. This split face study showed a highly significant difference with facial lifting on the treated side. Mesotox injection points vary based on the clinical indication and area being treated.

The treatment of dynamic muscles using standard neuromodulator dosing protocols include the treatment of the glabella, crow’s feet, forehead lines, masseter hypertrophy, bunny lines, gummy smile, perioral lines, mentalis hypertonia, platysmal bands, and marionette lines.

However, hyperdilute neuromodulators or Microtox can effectively be used alone or in combination with standard dosing for the following off-label uses. Used in combination with standard dosing of the forehead lines, I use Microtox in the lateral brow to soften the frontalis muscle without dropping the brow in patients with a low-set brow or lid laxity. I also use it for the jelly roll of the eyes and to open the aperture of the eyes. Along the nose, Microtox can also be used to treat a sagging nasal tip, decrease the width of the ala, and treat overactive facial muscles adjacent to the nose resulting in an overactive nasolabial fold.

Similarly, Microtox can be used to treat lateral smile lines and downward extensions of the crow’s feet. In all of the aforementioned treatment areas, I recommend approximately 0.5-1 U of toxin in each area divided at 1-cm intervals.Mesotox and Microtox are both highly effective strategies to treat the aging face. However, the nomenclature is not interchangeable. I propose that the term Mesotox be used only to articulate or define the superficial injection of a neuromodulator for the improvement of the skin that does not involve the injection into or paralysis of a cutaneous muscle (“tox” being used generically for all neuromodulators). I also propose that the term Microtox should be used to define the dilution of a neuromodulator beyond the manufacturer-recommended dilution protocols – used for the paralysis of a cutaneous muscle. In addition, I recommend that the terms MicroBotox and MesoBotox no longer be used. These procedures all have risks, and adverse events associated with Microtox and Mesotox are similar to those of any neuromodulator injection at FDA-recommended maximum doses, and dilution and storage protocols and proper injection techniques need to be followed. Expertise and training is crucial and treatment by a board-certified dermatologist or plastic surgeon is imperative.

 

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to her at [email protected]. Dr. Talakoub had no relevant disclosures.

References

Awaida CJ et al. Plast Reconstr Surg. 2018 Sep;142(3):640-9.

Calvani F et al. Plast Surg (Oakv). 2019 May;27(2):156-61.

Iranmanesh B et al. J Cosmet Dermatol. 2022 Oct;21(10):4160-70.

Kandhari R et al. J Cutan Aesthet Surg. 2022 Apr-Jun;15(2):101-7.

Lewandowski M et al. Molecules. 2022 May 13;27(10):3143.

Mammucari M et al. Eur Rev Med Pharmacol Sci. 2011 Jun;15(6):682-94.

Park KY et al. Ann Dermatol. 2018 Dec;30(6):688-93.

Pistor M. Chir Dent Fr. 1976;46:59-60.

Rho NK, Gil YC. Toxins (Basel). 2021 Nov 19;13(11):817.

Wu WTL. Plast Reconstr Surg. 2015 Nov;136(5 Suppl):92S-100S.

Zhang H et al. Clin Cosmet Investig Dermatol. 2021 Apr 30;14:407-17.