Opinion

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment. In 2022, a total of 160 new references were added to the previous year’s GOLD report.

According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.

These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.

The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.

In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.

In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.

It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.

Medications and treatment goals for patients with COPD

Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.

The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV₁) alone lacks precision to predict exacerbations or death.

Vaccines and pulmonary rehabilitation recommended

The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.

An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.

In patients with hypoxemia, supplemental oxygen should be titrated to a target O₂ saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.

Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.

Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.

COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.¹ Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.² When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.³

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),⁴ referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.⁴ Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.⁴

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.¹ Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.² When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.³

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),⁴ referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.⁴ Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.⁴

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

Historically, the role of genetic testing has been to identify familial cancer syndromes and initiate cascade testing. If a germline pathogenic variant is found in an individual, cascade testing involves genetic counseling and testing of blood relatives, starting with those closest in relation to the proband, to identify other family members at high hereditary cancer risk. Once testing identifies those family members at higher cancer risk, these individuals can be referred for risk-reducing procedures. They can undergo screening tests starting at an earlier age and/or increased frequency to help prevent invasive cancer or diagnose it at an earlier stage.

Genetic testing can also inform prognosis. While women with a BRCA1 or BRCA2 mutation are at higher risk of developing ovarian cancer compared with the baseline population, the presence of a germline BRCA mutation has been shown to confer improved survival compared with no BRCA mutation (BRCA wild type). However, more recent data have shown that when long-term survival was analyzed, the prognostic benefit seen in patients with a germline BRCA mutation was lost. The initial survival advantage seen in this population may be related to increased sensitivity to treatment. There appears to be improved response to platinum therapy, which is the standard of care for upfront treatment, in germline BRCA mutation carriers.

Most recently, genetic testing has been used to guide treatment decisions in gynecologic cancers. In 2014, the first poly ADP-ribose polymerase (PARP) inhibitor, olaparib, received Food and Drug Administration approval for the treatment of recurrent ovarian cancer in the presence of a germline BRCA mutation. Now there are multiple PARP inhibitors that have FDA approval for ovarian cancer treatment, some as frontline treatment.

Previous data indicate that 13%-18% of women with ovarian cancer have a germline BRCA mutation that places them at increased risk of hereditary ovarian cancer.¹ Current guidelines from the American Society of Clinical Oncology, the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists recommend universal genetic counseling and testing for patients diagnosed with epithelial ovarian cancer. Despite these guidelines, rates of referral for genetic counseling and completion of genetic testing are low.

There has been improvement for both referrals and testing since the publication of the 2014 SGO clinical practice statement on genetic testing for ovarian cancer patients, which recommended that all women, even those without any significant family history, should receive genetic counseling and be offered genetic testing.² When including only studies that collected data after the publication of the 2014 SGO clinical practice statement on genetic testing, a recent systematic review found that 64% of patients were referred for genetic counseling and 63% underwent testing.³

Clinical interventions to target genetic evaluation appear to improve uptake of both counseling and testing. These interventions include using telemedicine to deliver genetic counseling services, mainstreaming (counseling and testing are provided in an oncology clinic by nongenetics specialists), having a genetic counselor within the clinic, and performing reflex testing. With limited numbers of genetic counselors (and even further limited numbers of cancer-specific genetic counselors),⁴ referral for genetic counseling before testing is often challenging and may not be feasible. There is continued need for strategies to help overcome the barrier to accessing genetic counseling.

While the data are limited, there appear to be significant disparities in rates of genetic testing. Genetic counseling and testing were completed by White (43% and 40%) patients more frequently than by either Black (24% and 26%) or Asian (23% and 14%) patients.⁴ Uninsured patients were about half as likely (23% vs. 47%) to complete genetic testing as were those with private insurance.⁴

Genetic testing is an important tool to help identify individuals and families at risk of having hereditary cancer syndromes. This identification allows us to prevent many cancers and identify others while still early stage, significantly decreasing the health care and financial burden on our society and improving outcomes for patients. While we have seen improvement in rates of referral for genetic counseling and testing, we are still falling short. Given the shortage of genetic counselors, it is imperative that we find solutions to ensure continued and improved access to genetic testing for our patients.
 

Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Norquist BM et al. JAMA Oncol. 2016;2(4):482-90.

2. SGO Clinical Practice Statement. 2014 Oct 1.

3. Lin J et al. Gynecol Oncol. 2021;162(2):506-16.

4. American Society of Clinical Oncology. J Oncol Pract. 2016 Apr;12(4):339-83.

The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

The road to hell is paved with good intentions – especially true in clinical research. A Food and Drug Administration press release notes, “Historically, children were not included in clinical trials because of a misperception that excluding them from research was in fact protecting them. This resulted in many FDA-approved, licensed, cleared, or authorized drugs, biological products, and medical devices lacking pediatric-specific labeling information.” In an effort to improve on this situation, the FDA published in September 2022 a proposed new draft guidance on performing research with children that is open for public comment for 3 months.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

One of the more baffling decisions the CDC made during this pandemic was when they reduced the duration of isolation after a positive COVID test from 10 days to 5 days and did not require a negative antigen test to end isolation.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. He disclosed no relevant financial relationships.

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

It is assumed that psychiatrists in general, but particularly in academia, are progressive liberals. There is evidence to support this idea, with a survey finding that more than three-quarters of U.S. psychiatrists are registered Democrats.¹

Other corroborating factors to our field’s progressive tendency include the publication of pseudo-political books like “The Dangerous Case of Donald Trump: 27 Psychiatrists and Mental Health Experts Assess a President” – without a well-known equivalent on the other side.

Additionally, psychiatry has in the recent past, rightfully spent significant effort examining the disproportional trauma faced by patients with underprivileged backgrounds, which is often seen as a political position. The American Psychiatric Association has itself taken a stance on the national debate about abortion to warn against the psychiatric consequences of the Dobbs v. Jackson Supreme Court decision despite the clear political statement it makes.

We understand a likely rationale for psychiatry’s liberal tendency. Most psychiatrists support political objectives that provide resources for the treatment of the severely mentally ill. In general, the psychosocial consequences of mental illness place a downward economic pressure on our patients that leads to poverty and its associated traumas that then tend to feedback to worsen the severity of the illness itself. It is thus natural for psychiatry to promote political causes such as progressivism that focus on the needs of economically and socially struggling communities. If one posits a natural role for psychiatry in promoting the interests of patients, then it is a short leap to psychiatry promoting the political causes of the underprivileged, often in the form of endorsing the Democratic party.

As a result, a proportion of patients come into psychiatric treatment with expectations that their providers will negatively judge them and possibly punish their conservative beliefs or Republican political affiliation. Herein lies a question – “Is psychiatry willing to make 46.9% of Americans uncomfortable?” How should psychiatry address the 46.9% of Americans who voted Republican during the 2020 presidential election? In our desire to support the disadvantaged, how political are we willing to get and at what cost? While we cannot speak for the field as a whole, it is our concern that a vast percentage of Americans feel alienated from talking to us, which is particularly problematic in a field based on mutual trust and understanding.

Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Sanger-Katz M. Your surgeon is probably a Republican, your psychiatrist probably a Democrat. New York Times. 2016 Oct 6.

2. Ba B et al. Who are the police? Descriptive representation in the coercive arm of government. 2022 Mar 21.

3. Rainey J. Union leader tells Republican convention why cops back Trump. Los Angeles Times. 2020 Aug 26.

4. Igielnik R et al. Trump draws stronger support from veterans than from the public on leadership of U.S. military. Pew Research Center. 2019 July 10.

It is assumed that psychiatrists in general, but particularly in academia, are progressive liberals. There is evidence to support this idea, with a survey finding that more than three-quarters of U.S. psychiatrists are registered Democrats.¹

Other corroborating factors to our field’s progressive tendency include the publication of pseudo-political books like “The Dangerous Case of Donald Trump: 27 Psychiatrists and Mental Health Experts Assess a President” – without a well-known equivalent on the other side.

Additionally, psychiatry has in the recent past, rightfully spent significant effort examining the disproportional trauma faced by patients with underprivileged backgrounds, which is often seen as a political position. The American Psychiatric Association has itself taken a stance on the national debate about abortion to warn against the psychiatric consequences of the Dobbs v. Jackson Supreme Court decision despite the clear political statement it makes.

We understand a likely rationale for psychiatry’s liberal tendency. Most psychiatrists support political objectives that provide resources for the treatment of the severely mentally ill. In general, the psychosocial consequences of mental illness place a downward economic pressure on our patients that leads to poverty and its associated traumas that then tend to feedback to worsen the severity of the illness itself. It is thus natural for psychiatry to promote political causes such as progressivism that focus on the needs of economically and socially struggling communities. If one posits a natural role for psychiatry in promoting the interests of patients, then it is a short leap to psychiatry promoting the political causes of the underprivileged, often in the form of endorsing the Democratic party.

As a result, a proportion of patients come into psychiatric treatment with expectations that their providers will negatively judge them and possibly punish their conservative beliefs or Republican political affiliation. Herein lies a question – “Is psychiatry willing to make 46.9% of Americans uncomfortable?” How should psychiatry address the 46.9% of Americans who voted Republican during the 2020 presidential election? In our desire to support the disadvantaged, how political are we willing to get and at what cost? While we cannot speak for the field as a whole, it is our concern that a vast percentage of Americans feel alienated from talking to us, which is particularly problematic in a field based on mutual trust and understanding.

Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Sanger-Katz M. Your surgeon is probably a Republican, your psychiatrist probably a Democrat. New York Times. 2016 Oct 6.

2. Ba B et al. Who are the police? Descriptive representation in the coercive arm of government. 2022 Mar 21.

3. Rainey J. Union leader tells Republican convention why cops back Trump. Los Angeles Times. 2020 Aug 26.

4. Igielnik R et al. Trump draws stronger support from veterans than from the public on leadership of U.S. military. Pew Research Center. 2019 July 10.

It is assumed that psychiatrists in general, but particularly in academia, are progressive liberals. There is evidence to support this idea, with a survey finding that more than three-quarters of U.S. psychiatrists are registered Democrats.¹

Other corroborating factors to our field’s progressive tendency include the publication of pseudo-political books like “The Dangerous Case of Donald Trump: 27 Psychiatrists and Mental Health Experts Assess a President” – without a well-known equivalent on the other side.

Additionally, psychiatry has in the recent past, rightfully spent significant effort examining the disproportional trauma faced by patients with underprivileged backgrounds, which is often seen as a political position. The American Psychiatric Association has itself taken a stance on the national debate about abortion to warn against the psychiatric consequences of the Dobbs v. Jackson Supreme Court decision despite the clear political statement it makes.

We understand a likely rationale for psychiatry’s liberal tendency. Most psychiatrists support political objectives that provide resources for the treatment of the severely mentally ill. In general, the psychosocial consequences of mental illness place a downward economic pressure on our patients that leads to poverty and its associated traumas that then tend to feedback to worsen the severity of the illness itself. It is thus natural for psychiatry to promote political causes such as progressivism that focus on the needs of economically and socially struggling communities. If one posits a natural role for psychiatry in promoting the interests of patients, then it is a short leap to psychiatry promoting the political causes of the underprivileged, often in the form of endorsing the Democratic party.

As a result, a proportion of patients come into psychiatric treatment with expectations that their providers will negatively judge them and possibly punish their conservative beliefs or Republican political affiliation. Herein lies a question – “Is psychiatry willing to make 46.9% of Americans uncomfortable?” How should psychiatry address the 46.9% of Americans who voted Republican during the 2020 presidential election? In our desire to support the disadvantaged, how political are we willing to get and at what cost? While we cannot speak for the field as a whole, it is our concern that a vast percentage of Americans feel alienated from talking to us, which is particularly problematic in a field based on mutual trust and understanding.

Dr. Lehman is a professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Sanger-Katz M. Your surgeon is probably a Republican, your psychiatrist probably a Democrat. New York Times. 2016 Oct 6.

2. Ba B et al. Who are the police? Descriptive representation in the coercive arm of government. 2022 Mar 21.

3. Rainey J. Union leader tells Republican convention why cops back Trump. Los Angeles Times. 2020 Aug 26.

4. Igielnik R et al. Trump draws stronger support from veterans than from the public on leadership of U.S. military. Pew Research Center. 2019 July 10.

A systematic review was recently conducted by Wu and colleagues examining the risk of blindness associated with platelet-rich plasma (PRP) injection. In dermatology, PRP is used more commonly now than 5 years ago to promote hair growth with injections on the scalp, as an adjunct to microneedling procedures, and sometimes – in a similar way to facial fillers – to improve volume loss, and skin tone and texture (particularly to the tear trough region).

The analysis of four studies revealed seven cases of unilateral blindness or vision impairment associated with PRP injections. All cases were reported after use of PRP as a facial injection, not with PRP scalp injection or with microneedling. Total unilateral blindness occurred in all cases. In one of the seven reported cases, the patient experienced recovery of vision after 3 months, but with some residual deficits noted on the ophthalmologist examination. In this case, the patient was evaluated and treated by an ophthalmologist within 3 hours of symptom onset.

In addition, four cases were reported from Venezuela, one from the United States, one from the United Kingdom, and one from Malaysia. Similar to reports of blindness with facial fillers, the most common injection site reported with this adverse effect was the glabella (five cases);

Other reports involved injections of the forehead (two), followed by the nasolabial fold (one), lateral canthus (one), and temporomandibular joint (one). Two of the seven patients received injections at more than one site, resulting in the total number of injections reported (10) being higher than the number of patients.

The risk of blindness is inherent with deep injection into a vessel that anastomoses with the blood supply to the eye. No mention was made as to whether PRP or platelet-rich fibrin was used. Other details are lacking from the original articles as to injection technique and whether or not cannula injection was used. No treatment was attempted in four of seven cases.

As plasma is native to the arteries and dissolves in the blood stream naturally, the mechanism as to why retinal artery occlusion or blindness would occur is not completely clear. One theory is that it is volume related and results from the speed of injection, causing a large rapid bolus that temporarily occludes or compresses an involved vessel.

Another theory is that damage to the vessel results from the injection itself or injection technique, leading to a clotting cascade and clot of the involved vessel with subsequent retrograde flow or blockade of the retinal artery. But if this were the case, we would expect to hear about more cases of clots leading to vascular occlusion or skin necrosis, which does not typically occur or we do not hear about.

Details about proper collection materials and technique or mixing with some other materials are also unknown in these cases, thus leaving the possibility that a more occlusive material may have been injected, as opposed to the fluid-like composition of the typical PRP preparation.With regards to risk with scalp PRP injection, the frontal scalp does receive blood supply from the supratrochlear artery that anastomoses with the angular artery of the face – both of which anastomose with the retinal artery (where occlusion would occur via back flow). The scalp tributaries are small and far enough away from the retina at that point that risk of back flow the to retinal artery should be minimal. Additionally, no reports of vascular occlusion from PRP scalp injection leading to skin necrosis have ever been reported. Of note, this is also not a risk that has been reported with the use of PRP with microneedling procedures, where PRP is placed on top of the skin before, during and after microneedling.

Anything that occludes the blood supply to the eye, whether it be fat, filler, or PRP, has an inherent risk of blindness. As there is no reversal agent or designated treatment for PRP occlusion, care must be taken to minimize risk, including awareness of anatomy and avoidance of injection into high risk areas, and cannula use where appropriate. Gentle, slow, low-volume administration, and when possible, use of a retrograde injection technique, may also be helpful.
 

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

A systematic review was recently conducted by Wu and colleagues examining the risk of blindness associated with platelet-rich plasma (PRP) injection. In dermatology, PRP is used more commonly now than 5 years ago to promote hair growth with injections on the scalp, as an adjunct to microneedling procedures, and sometimes – in a similar way to facial fillers – to improve volume loss, and skin tone and texture (particularly to the tear trough region).

The analysis of four studies revealed seven cases of unilateral blindness or vision impairment associated with PRP injections. All cases were reported after use of PRP as a facial injection, not with PRP scalp injection or with microneedling. Total unilateral blindness occurred in all cases. In one of the seven reported cases, the patient experienced recovery of vision after 3 months, but with some residual deficits noted on the ophthalmologist examination. In this case, the patient was evaluated and treated by an ophthalmologist within 3 hours of symptom onset.

In addition, four cases were reported from Venezuela, one from the United States, one from the United Kingdom, and one from Malaysia. Similar to reports of blindness with facial fillers, the most common injection site reported with this adverse effect was the glabella (five cases);

Other reports involved injections of the forehead (two), followed by the nasolabial fold (one), lateral canthus (one), and temporomandibular joint (one). Two of the seven patients received injections at more than one site, resulting in the total number of injections reported (10) being higher than the number of patients.

The risk of blindness is inherent with deep injection into a vessel that anastomoses with the blood supply to the eye. No mention was made as to whether PRP or platelet-rich fibrin was used. Other details are lacking from the original articles as to injection technique and whether or not cannula injection was used. No treatment was attempted in four of seven cases.

As plasma is native to the arteries and dissolves in the blood stream naturally, the mechanism as to why retinal artery occlusion or blindness would occur is not completely clear. One theory is that it is volume related and results from the speed of injection, causing a large rapid bolus that temporarily occludes or compresses an involved vessel.

Another theory is that damage to the vessel results from the injection itself or injection technique, leading to a clotting cascade and clot of the involved vessel with subsequent retrograde flow or blockade of the retinal artery. But if this were the case, we would expect to hear about more cases of clots leading to vascular occlusion or skin necrosis, which does not typically occur or we do not hear about.

Details about proper collection materials and technique or mixing with some other materials are also unknown in these cases, thus leaving the possibility that a more occlusive material may have been injected, as opposed to the fluid-like composition of the typical PRP preparation.With regards to risk with scalp PRP injection, the frontal scalp does receive blood supply from the supratrochlear artery that anastomoses with the angular artery of the face – both of which anastomose with the retinal artery (where occlusion would occur via back flow). The scalp tributaries are small and far enough away from the retina at that point that risk of back flow the to retinal artery should be minimal. Additionally, no reports of vascular occlusion from PRP scalp injection leading to skin necrosis have ever been reported. Of note, this is also not a risk that has been reported with the use of PRP with microneedling procedures, where PRP is placed on top of the skin before, during and after microneedling.

Anything that occludes the blood supply to the eye, whether it be fat, filler, or PRP, has an inherent risk of blindness. As there is no reversal agent or designated treatment for PRP occlusion, care must be taken to minimize risk, including awareness of anatomy and avoidance of injection into high risk areas, and cannula use where appropriate. Gentle, slow, low-volume administration, and when possible, use of a retrograde injection technique, may also be helpful.
 

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

A systematic review was recently conducted by Wu and colleagues examining the risk of blindness associated with platelet-rich plasma (PRP) injection. In dermatology, PRP is used more commonly now than 5 years ago to promote hair growth with injections on the scalp, as an adjunct to microneedling procedures, and sometimes – in a similar way to facial fillers – to improve volume loss, and skin tone and texture (particularly to the tear trough region).

The analysis of four studies revealed seven cases of unilateral blindness or vision impairment associated with PRP injections. All cases were reported after use of PRP as a facial injection, not with PRP scalp injection or with microneedling. Total unilateral blindness occurred in all cases. In one of the seven reported cases, the patient experienced recovery of vision after 3 months, but with some residual deficits noted on the ophthalmologist examination. In this case, the patient was evaluated and treated by an ophthalmologist within 3 hours of symptom onset.

In addition, four cases were reported from Venezuela, one from the United States, one from the United Kingdom, and one from Malaysia. Similar to reports of blindness with facial fillers, the most common injection site reported with this adverse effect was the glabella (five cases);

Other reports involved injections of the forehead (two), followed by the nasolabial fold (one), lateral canthus (one), and temporomandibular joint (one). Two of the seven patients received injections at more than one site, resulting in the total number of injections reported (10) being higher than the number of patients.

The risk of blindness is inherent with deep injection into a vessel that anastomoses with the blood supply to the eye. No mention was made as to whether PRP or platelet-rich fibrin was used. Other details are lacking from the original articles as to injection technique and whether or not cannula injection was used. No treatment was attempted in four of seven cases.

As plasma is native to the arteries and dissolves in the blood stream naturally, the mechanism as to why retinal artery occlusion or blindness would occur is not completely clear. One theory is that it is volume related and results from the speed of injection, causing a large rapid bolus that temporarily occludes or compresses an involved vessel.

Another theory is that damage to the vessel results from the injection itself or injection technique, leading to a clotting cascade and clot of the involved vessel with subsequent retrograde flow or blockade of the retinal artery. But if this were the case, we would expect to hear about more cases of clots leading to vascular occlusion or skin necrosis, which does not typically occur or we do not hear about.

Details about proper collection materials and technique or mixing with some other materials are also unknown in these cases, thus leaving the possibility that a more occlusive material may have been injected, as opposed to the fluid-like composition of the typical PRP preparation.With regards to risk with scalp PRP injection, the frontal scalp does receive blood supply from the supratrochlear artery that anastomoses with the angular artery of the face – both of which anastomose with the retinal artery (where occlusion would occur via back flow). The scalp tributaries are small and far enough away from the retina at that point that risk of back flow the to retinal artery should be minimal. Additionally, no reports of vascular occlusion from PRP scalp injection leading to skin necrosis have ever been reported. Of note, this is also not a risk that has been reported with the use of PRP with microneedling procedures, where PRP is placed on top of the skin before, during and after microneedling.

Anything that occludes the blood supply to the eye, whether it be fat, filler, or PRP, has an inherent risk of blindness. As there is no reversal agent or designated treatment for PRP occlusion, care must be taken to minimize risk, including awareness of anatomy and avoidance of injection into high risk areas, and cannula use where appropriate. Gentle, slow, low-volume administration, and when possible, use of a retrograde injection technique, may also be helpful.
 

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

A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.

Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.

There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.

The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.

Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.

When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.

Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
 

References

Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.

Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.

A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.

Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.

There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.

The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.

Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.

When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.

Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
 

References

Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.

Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.

A biopsy of the lesion was performed that showed a well-defined nodulocystic tumor composed of nests of basaloid cells that are undergoing trichilemmal keratinization. Shadow cells are seen as well as small areas of calcification. There is also a histiocytic infiltrate with multinucleated giant cells. The histologic diagnosis is of a pilomatrixoma.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, was first described in 1880, as a tumor of sebaceous gland origin. Later, in 1961, Robert Forbis Jr, MD, and Elson B. Helwig, MD, coined the term pilomatrixoma to describe the hair follicle matrix as the source of the tumor. Pilomatrixomas are commonly seen in the pediatric population, usually in children between 8 and 13 years of age. Our patient is one of the youngest described. The lesions are commonly seen on the face and neck in about 70% of the cases followed by the upper extremities, back, and legs. Clinically, the lesions appear as a firm dermal papule or nodule, which moves freely and may have associated erythema on the skin surface or a blueish gray hue on the underlying skin.

Most pilomatrixomas that have been studied have shown a mutation in Exon 3 of the beta-catenin gene (CTNNB1). The beta-catenin molecule is a subunit of the cadherin protein, which is part of an important pathway in the terminal hair follicle differentiation. Beta-catenin also plays an important role in the Wnt pathway, which regulates cell fate as well as early embryonic patterning. Beta-catenin is responsible for forming adhesion junctions among cells. There have also been immunohistochemical studies that have shown a BCL2 proto-oncogene overexpression to pilomatrixoma.

There are several genetic syndromes that have been associated with the presence of pilomatrixomas: Turner syndrome (XO chromosome abnormality associated with short stature and cardiac defects), Gardner syndrome (polyposis coli and colon and rectal cancer), myotonic dystrophy, Rubinstein-Taybi syndrome (characterized by broad thumbs and toes, short stature, distinctive facial features, and varying degrees of intellectual disability), and trisomy 9. On physical examination our patient didn’t present with any of the typical features or history that could suggest any of these syndromes. A close follow-up and evaluation by a geneticist was recommended because after the initial visit she developed a second lesion on the forehead.

The differential diagnosis for this lesion includes other cysts that may occur on the ear such as epidermal inclusion cyst or dermoid cysts, though these lesions do not tend to be as firm as pilomatrixomas are, which can help with the diagnosis. Dermoid cysts are made of dermal and epidermal components. They are usually present at birth and are commonly seen on the scalp and the periorbital face.

Keloids are rubbery nodules of scar tissue that can form on sites of trauma, and although the lesion occurred after she had her ears pierced, the consistency and rapid growth of the lesion as well as the pathological description made this benign fibrous growth less likely.

When pilomatrixomas are inflamed they can be confused with vascular growths: in this particular case, a hemangioma or another vascular tumor such as a tufted angioma or kaposiform hemangioendothelioma. An ultrasound of the lesion could have helped in the differential diagnosis of the lesion.

Pilomatrixomas can grow significantly and in some cases get inflamed or infected. Surgical management of pilomatrixomas is often required because the lesions do not regress spontaneously.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
 

References

Forbis R Jr and Helwig EB. Arch Dermatol 1961;83:606-18.

Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016 Jun;85:148-53.

A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.^1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.^3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.^3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.⁴ Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.³ In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.

Active ingredients of bilberry

Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.⁷

Anneli Salo/CC BY-SA 3.0

A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.⁸

The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.⁶

In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.⁹

Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.¹⁰

Activity against allergic contact dermatitis

Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.⁸ A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.¹¹

Antioxidant and anti-inflammatory activity

Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.¹²

In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.² A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.¹³

In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.¹⁴

Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.¹⁵

Skin preparations

In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.¹

Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.¹⁶

V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.¹⁷

Summary

While research, particularly in the form of randomized controlled trials, is called for, bilberry appears to be a safe and effective ingredient that provides skin-protective antioxidant and anti-inflammatory activity. It is an ideal ingredient for use with skin lighteners because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.

2. Svobodová A et al. Biofactors. 2008;33(4):249-66.

3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).

4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.

5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.

6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.

7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.

8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.

9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.

10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.

11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.

12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.

13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.

14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.

15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.

16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.

17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.

A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.^1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.^3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.^3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.⁴ Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.³ In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.

Active ingredients of bilberry

Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.⁷

Anneli Salo/CC BY-SA 3.0

A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.⁸

The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.⁶

In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.⁹

Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.¹⁰

Activity against allergic contact dermatitis

Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.⁸ A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.¹¹

Antioxidant and anti-inflammatory activity

Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.¹²

In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.² A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.¹³

In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.¹⁴

Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.¹⁵

Skin preparations

In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.¹

Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.¹⁶

V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.¹⁷

Summary

While research, particularly in the form of randomized controlled trials, is called for, bilberry appears to be a safe and effective ingredient that provides skin-protective antioxidant and anti-inflammatory activity. It is an ideal ingredient for use with skin lighteners because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.

2. Svobodová A et al. Biofactors. 2008;33(4):249-66.

3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).

4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.

5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.

6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.

7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.

8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.

9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.

10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.

11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.

12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.

13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.

14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.

15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.

16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.

17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.

A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.^1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.^3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.^3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.⁴ Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.³ In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.

Active ingredients of bilberry

Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.⁷

Anneli Salo/CC BY-SA 3.0

A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.⁸

The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.⁶

In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.⁹

Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.¹⁰

Activity against allergic contact dermatitis

Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.⁸ A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.¹¹

Antioxidant and anti-inflammatory activity

Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.¹²

In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.² A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.¹³

In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.¹⁴

Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.¹⁵

Skin preparations

In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.¹

Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.¹⁶

V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.¹⁷

Summary

While research, particularly in the form of randomized controlled trials, is called for, bilberry appears to be a safe and effective ingredient that provides skin-protective antioxidant and anti-inflammatory activity. It is an ideal ingredient for use with skin lighteners because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.

2. Svobodová A et al. Biofactors. 2008;33(4):249-66.

3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).

4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.

5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.

6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.

7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.

8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.

9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.

10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.

11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.

12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.

13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.

14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.

15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.

16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.

17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.

“How did we miss out on that?” “What?” my physician friend replied as we stood in line at the coffee cart. “Root cause. I mean, we invented this idea and now all these naturopaths and functional medicine quacks are gettin’ rich off it.” “Take it easy,” he says. “Just order a coffee.”

It’s hard not to be indignant. I had a morning clinic with three patients insisting I find the “root cause” of their problem. Now, if one had flagellate dermatitis after eating Asian mushroom soup, I’d have said “Root cause? Shiitake mushrooms!” and walked out like Costanza in Seinfeld, “All right, that’s it for me! Be good everybody!”

Alas no. They had perioral dermatitis, alopecia areata, eczema – no satisfying “roots” for walk-off answers.

There is a universal desire to find the proximal cause for problems. Patients often want to know it so that we address the root of their trouble and not just cut off the branches. This is deeply gratifying for those who want not only to know why, but also to have agency in how to control their disease. For example, if they believe the root cause of perioral dermatitis was excess yeast, then eating a “candida diet’’ should do the trick! Food sensitivities, hormones, and heavy metals round out the top suspects that root cause patients want to talk about.

Of course, patients have been asking about this for a long time, but lately, the root cause visit seems to be on trend. Check out any hip primary care start-up such as One Medical or any hot direct-to-consumer virtual offering such as ParsleyHealth and you will see root-cause everywhere. Our patients are expecting us to address it, or it seems they will find someone cooler who will.

Yet, it wasn’t the slick marketing team at ParsleyHeath who invented the “root cause doctor visit.” We did. It’s an idea that started with our Greek physician ancestors. Breaking from the diviners and priests, we were the first “naturalists” positing that there was a natural, not a divine cause for illness. The cardinal concept in the Hippocratic Corpus was that health was an equilibrium and illness an imbalance. They didn’t have dehydroepiandrosterone tests or mercury levels, but did have bodily fluids. Yellow bile, black bile, blood, and phlegm, were the root of all root causes. A physician simply had to identify which was in excess or deficient and fix that to cure the disease. Interestingly, the word “diagnosis” appears only once in the Corpus. The word “Diagignoskein” appears occasionally but this describes studying thoroughly, not naming a diagnosis as we understand it.

Advances in chemistry in the 17th century meant physicians could add new theories, and new root causes. Now alkaline or other chemical elixirs were added to cure at the source. Since there was no verifiable evidence to prove causes, theories were adopted to provide some rational direction to treatment. In the 18th century, physicians such as Dr. Benjamin Rush, one of the original faculty at the University of Pennsylvania school of medicine, taught that spasms of the arteries were the root cause of illnesses. “Heroic” treatments such as extreme bloodletting were the cure. (Note, those patients who survived us kept coming back to us for more).

Scientific knowledge and diagnostic technologies led to more and more complex and abstruse causes. Yet, as we became more precise and effective, our explanations became less satisfying to our patients. I can diagnose and readily treat perioral dermatitis, yet I’m hard pressed to give an answer to its root cause. “Root cause? Yes. Just apply this pimecrolimus cream for a couple of weeks and it’ll be better! All right, that’s it for me! Be good everybody!”

You’ll have to do better, George.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

“How did we miss out on that?” “What?” my physician friend replied as we stood in line at the coffee cart. “Root cause. I mean, we invented this idea and now all these naturopaths and functional medicine quacks are gettin’ rich off it.” “Take it easy,” he says. “Just order a coffee.”

It’s hard not to be indignant. I had a morning clinic with three patients insisting I find the “root cause” of their problem. Now, if one had flagellate dermatitis after eating Asian mushroom soup, I’d have said “Root cause? Shiitake mushrooms!” and walked out like Costanza in Seinfeld, “All right, that’s it for me! Be good everybody!”

Alas no. They had perioral dermatitis, alopecia areata, eczema – no satisfying “roots” for walk-off answers.

There is a universal desire to find the proximal cause for problems. Patients often want to know it so that we address the root of their trouble and not just cut off the branches. This is deeply gratifying for those who want not only to know why, but also to have agency in how to control their disease. For example, if they believe the root cause of perioral dermatitis was excess yeast, then eating a “candida diet’’ should do the trick! Food sensitivities, hormones, and heavy metals round out the top suspects that root cause patients want to talk about.

Of course, patients have been asking about this for a long time, but lately, the root cause visit seems to be on trend. Check out any hip primary care start-up such as One Medical or any hot direct-to-consumer virtual offering such as ParsleyHealth and you will see root-cause everywhere. Our patients are expecting us to address it, or it seems they will find someone cooler who will.

Yet, it wasn’t the slick marketing team at ParsleyHeath who invented the “root cause doctor visit.” We did. It’s an idea that started with our Greek physician ancestors. Breaking from the diviners and priests, we were the first “naturalists” positing that there was a natural, not a divine cause for illness. The cardinal concept in the Hippocratic Corpus was that health was an equilibrium and illness an imbalance. They didn’t have dehydroepiandrosterone tests or mercury levels, but did have bodily fluids. Yellow bile, black bile, blood, and phlegm, were the root of all root causes. A physician simply had to identify which was in excess or deficient and fix that to cure the disease. Interestingly, the word “diagnosis” appears only once in the Corpus. The word “Diagignoskein” appears occasionally but this describes studying thoroughly, not naming a diagnosis as we understand it.

Advances in chemistry in the 17th century meant physicians could add new theories, and new root causes. Now alkaline or other chemical elixirs were added to cure at the source. Since there was no verifiable evidence to prove causes, theories were adopted to provide some rational direction to treatment. In the 18th century, physicians such as Dr. Benjamin Rush, one of the original faculty at the University of Pennsylvania school of medicine, taught that spasms of the arteries were the root cause of illnesses. “Heroic” treatments such as extreme bloodletting were the cure. (Note, those patients who survived us kept coming back to us for more).

Scientific knowledge and diagnostic technologies led to more and more complex and abstruse causes. Yet, as we became more precise and effective, our explanations became less satisfying to our patients. I can diagnose and readily treat perioral dermatitis, yet I’m hard pressed to give an answer to its root cause. “Root cause? Yes. Just apply this pimecrolimus cream for a couple of weeks and it’ll be better! All right, that’s it for me! Be good everybody!”

You’ll have to do better, George.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

“How did we miss out on that?” “What?” my physician friend replied as we stood in line at the coffee cart. “Root cause. I mean, we invented this idea and now all these naturopaths and functional medicine quacks are gettin’ rich off it.” “Take it easy,” he says. “Just order a coffee.”

It’s hard not to be indignant. I had a morning clinic with three patients insisting I find the “root cause” of their problem. Now, if one had flagellate dermatitis after eating Asian mushroom soup, I’d have said “Root cause? Shiitake mushrooms!” and walked out like Costanza in Seinfeld, “All right, that’s it for me! Be good everybody!”

Alas no. They had perioral dermatitis, alopecia areata, eczema – no satisfying “roots” for walk-off answers.

There is a universal desire to find the proximal cause for problems. Patients often want to know it so that we address the root of their trouble and not just cut off the branches. This is deeply gratifying for those who want not only to know why, but also to have agency in how to control their disease. For example, if they believe the root cause of perioral dermatitis was excess yeast, then eating a “candida diet’’ should do the trick! Food sensitivities, hormones, and heavy metals round out the top suspects that root cause patients want to talk about.

Of course, patients have been asking about this for a long time, but lately, the root cause visit seems to be on trend. Check out any hip primary care start-up such as One Medical or any hot direct-to-consumer virtual offering such as ParsleyHealth and you will see root-cause everywhere. Our patients are expecting us to address it, or it seems they will find someone cooler who will.

Yet, it wasn’t the slick marketing team at ParsleyHeath who invented the “root cause doctor visit.” We did. It’s an idea that started with our Greek physician ancestors. Breaking from the diviners and priests, we were the first “naturalists” positing that there was a natural, not a divine cause for illness. The cardinal concept in the Hippocratic Corpus was that health was an equilibrium and illness an imbalance. They didn’t have dehydroepiandrosterone tests or mercury levels, but did have bodily fluids. Yellow bile, black bile, blood, and phlegm, were the root of all root causes. A physician simply had to identify which was in excess or deficient and fix that to cure the disease. Interestingly, the word “diagnosis” appears only once in the Corpus. The word “Diagignoskein” appears occasionally but this describes studying thoroughly, not naming a diagnosis as we understand it.

Advances in chemistry in the 17th century meant physicians could add new theories, and new root causes. Now alkaline or other chemical elixirs were added to cure at the source. Since there was no verifiable evidence to prove causes, theories were adopted to provide some rational direction to treatment. In the 18th century, physicians such as Dr. Benjamin Rush, one of the original faculty at the University of Pennsylvania school of medicine, taught that spasms of the arteries were the root cause of illnesses. “Heroic” treatments such as extreme bloodletting were the cure. (Note, those patients who survived us kept coming back to us for more).

Scientific knowledge and diagnostic technologies led to more and more complex and abstruse causes. Yet, as we became more precise and effective, our explanations became less satisfying to our patients. I can diagnose and readily treat perioral dermatitis, yet I’m hard pressed to give an answer to its root cause. “Root cause? Yes. Just apply this pimecrolimus cream for a couple of weeks and it’ll be better! All right, that’s it for me! Be good everybody!”

You’ll have to do better, George.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

I have been noticing “jokes” lately about doctors. Magazine cartoons depict doctors as conveying a bad prognosis in abrupt, indirect, vague ways. I remember, from medical school, the joke about pediatricians being doctors for patients “from the waist up” – wimps about tough topics such as sexuality. As an inherently shy person, I have appreciated the structure of the contractual relationship with families that both gives me permission and requires me to be direct about topics that would not be socially acceptable to discuss in other relationships.

Examples include our asking about bowel movements, genital symptoms, marital conflict, past abortions, food insecurity, adherence to medication, history of trauma or discrimination, substance use, illegal conduct, and suicidal ideation, among others. By bringing up these topics nonjudgmentally and with skill, we are demonstrating openness and making it safe for the patient/parent to ask questions about their own concerns.

Since these may be topics for which we lack knowledge or have very little power to help, it is far easier to not bring them up. Yet failing to have the courage to elicit sensitive information may delay the correct diagnosis, result in inappropriate tests or treatments, or miss factors critical in either the cause or solution for the patient’s problems.

Historically, being a physician has conveyed a promise of confidentiality and always trying to do what is best for the patient. The fact that we had to swear an oath to do so may also indicate that these things are not easy to do.

Yes, we need a lot of knowledge to know what is truly in the patient’s best interest. But we need to take personal risks to do it as well. There have been times when a parent has shouted “That is none of your business” at me or stormed out. Although only one patient has ever connected when striking out at me, other clinicians have not been as lucky (or had such small patients); some have even been killed.

For those of us in private practice, upsetting a patient with our well-intentioned words may mean losing them from our income stream or having them post negative comments online, which may affect our reputation in the community. Patients may not return for needed follow-up if a conversation was too uncomfortable for them. Current political divisions make this even trickier.

These days anxiety about getting behind in seeing the next patient may be a covert reason for avoiding difficult conversations as tears or anger take extra time. Certainly, fears of these outcomes can make us hold back from talking about important but potentially upsetting topics.

Of course, courage does not just mean being direct with questions, stating your observations, or giving advice. Courage requires thoughtfulness about possible adverse outcomes and their effect on others. It is not just “stupid bravery,” to proceed even when sensing danger. Courage is thus best paired with skill. It is:

• Setting up potentially difficult discussions with privacy (from the child or parent), seating, and enough time to listen.
• Normalizing questions by saying “I ask all my patients about ...” so patients do not feel singled out.
• Asking the patient or family first what they think is going on and how their own culture might regard the issue.
• Using simple language and arranging a translator when needed.
• Not just stating facts but checking “to be sure I explained well enough” rather than setting a patient up to appear ignorant for not understanding.
• Offering to contact the patient or other family member/support soon to review what you said and answer more questions.
• Offering a second opinion option.
• Promising to get more information when you do not know.
• Always leaving room for hope and sharing in that hope with them.

And it is crucial to have a way to keep notes about past trauma or difficult topics for a patient so neither you nor subsequent clinicians unnecessarily ask about sensitive topics.

Courage includes facing difficult situations without undue delay. Making that call about an abnormal test result right away, even when you are tired and upset, takes courage. Each time you overcome your own reluctance it takes moral strength but tends to make future courageous acts easier. Speaking up to a specialist on rounds when you think he or she is incorrect takes courage to serve the patient’s best interest. Being willing to try a new workflow in your office takes the courage to risk looking awkward or being judged by your team, but can be essential to progress. Asking for help or an opinion, sometimes from a medical assistant or student, can take courage but may reduce status barriers and improve relationships. Standing up for your values when they are not popular may take courage in some organizations. It takes courage to admit a mistake, even when your mistake may not otherwise be noticed.

How can we grow in courage? T. Berry Brazelton, MD, was a model of courage for me during my training – able and willing to tell about a child’s delays or ask about a parent’s well-being with empathy and by giving hope. Dr. Brazelton, pediatrician, developer of the Neonatal Behavioral Assessment Scale, professor at Harvard Medical School and founder of its Child Development Unit, was a world-renowned educator about the development of children and founder of the Touchpoints program. Our goal should be to promise to partner with the family in dealing with the problem, no matter how difficult or tender. I hope you had role models who not only said what to do but also demonstrated it with patients.

We had the privilege of hearing stories of difficult situations from hundreds of pediatricians in group sessions over the years in the Collaborative Office Rounds program. What group members often said that they valued most from these sessions was hearing examples of words they might say in these cases, either modeled by the coleaders or suggested by their pediatrician peers. Opportunities to share the tough times with trusted empathic peers is an important resource rarer and thus even more worth securing for yourself.

Being courageous may not be natural part of your personality but Aristotle said, “We become what we repeatedly do.” Even if you do not consider yourself so now, with practice you can become courageous and reap its benefits for your patients and yourself.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

I have been noticing “jokes” lately about doctors. Magazine cartoons depict doctors as conveying a bad prognosis in abrupt, indirect, vague ways. I remember, from medical school, the joke about pediatricians being doctors for patients “from the waist up” – wimps about tough topics such as sexuality. As an inherently shy person, I have appreciated the structure of the contractual relationship with families that both gives me permission and requires me to be direct about topics that would not be socially acceptable to discuss in other relationships.

Examples include our asking about bowel movements, genital symptoms, marital conflict, past abortions, food insecurity, adherence to medication, history of trauma or discrimination, substance use, illegal conduct, and suicidal ideation, among others. By bringing up these topics nonjudgmentally and with skill, we are demonstrating openness and making it safe for the patient/parent to ask questions about their own concerns.

Since these may be topics for which we lack knowledge or have very little power to help, it is far easier to not bring them up. Yet failing to have the courage to elicit sensitive information may delay the correct diagnosis, result in inappropriate tests or treatments, or miss factors critical in either the cause or solution for the patient’s problems.

Historically, being a physician has conveyed a promise of confidentiality and always trying to do what is best for the patient. The fact that we had to swear an oath to do so may also indicate that these things are not easy to do.

Yes, we need a lot of knowledge to know what is truly in the patient’s best interest. But we need to take personal risks to do it as well. There have been times when a parent has shouted “That is none of your business” at me or stormed out. Although only one patient has ever connected when striking out at me, other clinicians have not been as lucky (or had such small patients); some have even been killed.

For those of us in private practice, upsetting a patient with our well-intentioned words may mean losing them from our income stream or having them post negative comments online, which may affect our reputation in the community. Patients may not return for needed follow-up if a conversation was too uncomfortable for them. Current political divisions make this even trickier.

These days anxiety about getting behind in seeing the next patient may be a covert reason for avoiding difficult conversations as tears or anger take extra time. Certainly, fears of these outcomes can make us hold back from talking about important but potentially upsetting topics.

Of course, courage does not just mean being direct with questions, stating your observations, or giving advice. Courage requires thoughtfulness about possible adverse outcomes and their effect on others. It is not just “stupid bravery,” to proceed even when sensing danger. Courage is thus best paired with skill. It is:

• Setting up potentially difficult discussions with privacy (from the child or parent), seating, and enough time to listen.
• Normalizing questions by saying “I ask all my patients about ...” so patients do not feel singled out.
• Asking the patient or family first what they think is going on and how their own culture might regard the issue.
• Using simple language and arranging a translator when needed.
• Not just stating facts but checking “to be sure I explained well enough” rather than setting a patient up to appear ignorant for not understanding.
• Offering to contact the patient or other family member/support soon to review what you said and answer more questions.
• Offering a second opinion option.
• Promising to get more information when you do not know.
• Always leaving room for hope and sharing in that hope with them.

And it is crucial to have a way to keep notes about past trauma or difficult topics for a patient so neither you nor subsequent clinicians unnecessarily ask about sensitive topics.

Courage includes facing difficult situations without undue delay. Making that call about an abnormal test result right away, even when you are tired and upset, takes courage. Each time you overcome your own reluctance it takes moral strength but tends to make future courageous acts easier. Speaking up to a specialist on rounds when you think he or she is incorrect takes courage to serve the patient’s best interest. Being willing to try a new workflow in your office takes the courage to risk looking awkward or being judged by your team, but can be essential to progress. Asking for help or an opinion, sometimes from a medical assistant or student, can take courage but may reduce status barriers and improve relationships. Standing up for your values when they are not popular may take courage in some organizations. It takes courage to admit a mistake, even when your mistake may not otherwise be noticed.

How can we grow in courage? T. Berry Brazelton, MD, was a model of courage for me during my training – able and willing to tell about a child’s delays or ask about a parent’s well-being with empathy and by giving hope. Dr. Brazelton, pediatrician, developer of the Neonatal Behavioral Assessment Scale, professor at Harvard Medical School and founder of its Child Development Unit, was a world-renowned educator about the development of children and founder of the Touchpoints program. Our goal should be to promise to partner with the family in dealing with the problem, no matter how difficult or tender. I hope you had role models who not only said what to do but also demonstrated it with patients.

We had the privilege of hearing stories of difficult situations from hundreds of pediatricians in group sessions over the years in the Collaborative Office Rounds program. What group members often said that they valued most from these sessions was hearing examples of words they might say in these cases, either modeled by the coleaders or suggested by their pediatrician peers. Opportunities to share the tough times with trusted empathic peers is an important resource rarer and thus even more worth securing for yourself.

Being courageous may not be natural part of your personality but Aristotle said, “We become what we repeatedly do.” Even if you do not consider yourself so now, with practice you can become courageous and reap its benefits for your patients and yourself.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

I have been noticing “jokes” lately about doctors. Magazine cartoons depict doctors as conveying a bad prognosis in abrupt, indirect, vague ways. I remember, from medical school, the joke about pediatricians being doctors for patients “from the waist up” – wimps about tough topics such as sexuality. As an inherently shy person, I have appreciated the structure of the contractual relationship with families that both gives me permission and requires me to be direct about topics that would not be socially acceptable to discuss in other relationships.

Examples include our asking about bowel movements, genital symptoms, marital conflict, past abortions, food insecurity, adherence to medication, history of trauma or discrimination, substance use, illegal conduct, and suicidal ideation, among others. By bringing up these topics nonjudgmentally and with skill, we are demonstrating openness and making it safe for the patient/parent to ask questions about their own concerns.

Since these may be topics for which we lack knowledge or have very little power to help, it is far easier to not bring them up. Yet failing to have the courage to elicit sensitive information may delay the correct diagnosis, result in inappropriate tests or treatments, or miss factors critical in either the cause or solution for the patient’s problems.

Historically, being a physician has conveyed a promise of confidentiality and always trying to do what is best for the patient. The fact that we had to swear an oath to do so may also indicate that these things are not easy to do.

Yes, we need a lot of knowledge to know what is truly in the patient’s best interest. But we need to take personal risks to do it as well. There have been times when a parent has shouted “That is none of your business” at me or stormed out. Although only one patient has ever connected when striking out at me, other clinicians have not been as lucky (or had such small patients); some have even been killed.

For those of us in private practice, upsetting a patient with our well-intentioned words may mean losing them from our income stream or having them post negative comments online, which may affect our reputation in the community. Patients may not return for needed follow-up if a conversation was too uncomfortable for them. Current political divisions make this even trickier.

These days anxiety about getting behind in seeing the next patient may be a covert reason for avoiding difficult conversations as tears or anger take extra time. Certainly, fears of these outcomes can make us hold back from talking about important but potentially upsetting topics.

Of course, courage does not just mean being direct with questions, stating your observations, or giving advice. Courage requires thoughtfulness about possible adverse outcomes and their effect on others. It is not just “stupid bravery,” to proceed even when sensing danger. Courage is thus best paired with skill. It is:

• Setting up potentially difficult discussions with privacy (from the child or parent), seating, and enough time to listen.
• Normalizing questions by saying “I ask all my patients about ...” so patients do not feel singled out.
• Asking the patient or family first what they think is going on and how their own culture might regard the issue.
• Using simple language and arranging a translator when needed.
• Not just stating facts but checking “to be sure I explained well enough” rather than setting a patient up to appear ignorant for not understanding.
• Offering to contact the patient or other family member/support soon to review what you said and answer more questions.
• Offering a second opinion option.
• Promising to get more information when you do not know.
• Always leaving room for hope and sharing in that hope with them.

And it is crucial to have a way to keep notes about past trauma or difficult topics for a patient so neither you nor subsequent clinicians unnecessarily ask about sensitive topics.

Courage includes facing difficult situations without undue delay. Making that call about an abnormal test result right away, even when you are tired and upset, takes courage. Each time you overcome your own reluctance it takes moral strength but tends to make future courageous acts easier. Speaking up to a specialist on rounds when you think he or she is incorrect takes courage to serve the patient’s best interest. Being willing to try a new workflow in your office takes the courage to risk looking awkward or being judged by your team, but can be essential to progress. Asking for help or an opinion, sometimes from a medical assistant or student, can take courage but may reduce status barriers and improve relationships. Standing up for your values when they are not popular may take courage in some organizations. It takes courage to admit a mistake, even when your mistake may not otherwise be noticed.

How can we grow in courage? T. Berry Brazelton, MD, was a model of courage for me during my training – able and willing to tell about a child’s delays or ask about a parent’s well-being with empathy and by giving hope. Dr. Brazelton, pediatrician, developer of the Neonatal Behavioral Assessment Scale, professor at Harvard Medical School and founder of its Child Development Unit, was a world-renowned educator about the development of children and founder of the Touchpoints program. Our goal should be to promise to partner with the family in dealing with the problem, no matter how difficult or tender. I hope you had role models who not only said what to do but also demonstrated it with patients.

We had the privilege of hearing stories of difficult situations from hundreds of pediatricians in group sessions over the years in the Collaborative Office Rounds program. What group members often said that they valued most from these sessions was hearing examples of words they might say in these cases, either modeled by the coleaders or suggested by their pediatrician peers. Opportunities to share the tough times with trusted empathic peers is an important resource rarer and thus even more worth securing for yourself.

Being courageous may not be natural part of your personality but Aristotle said, “We become what we repeatedly do.” Even if you do not consider yourself so now, with practice you can become courageous and reap its benefits for your patients and yourself.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].