The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

The clinical features and inflammatory mediators of adult-onset asthma were associated with distinct endotype groups defined by eosinophil and neutrophil levels, based on data from a real-life long term study of 203 patients.

Asthma is a chronic condition from lower respiratory tract inflammation composed of complex, heterogeneous endotypes with T2 helper cells being one way to distinguish between them. Endotypes have previously been suggested to have differing risks for asthma exacerbations and severity. However, clinical and biomarker information used for recognizing and targeting treatment is largely lacking in those subgroups other than eosinophilic asthma, according to Ella Flinkman, faculty of medicine and health technology, of Tampere University (Finland), and colleagues.

In a study published in The Journal of Allergy and Clinical Immunology: In Practice the researchers reported on their single-center 12-year follow-up phase II Seinäjoki Adult Asthma Study (SAAS). The included cohort of 203 patients had a median age of 58 years and 58% were women; all participants were originally diagnosed by a respiratory specialist physician as having new adult-onset asthma during the years 1999-2000 using asthma symptoms and objective lung function measurements.

To evaluate the association between clinical features and inflammation mediators to venous blood granulocytes this cohort was divided into paucigranulocytic (n = 108), neutrophilic (n = 60), eosinophilic (n = 21), and mixed granulocytic (n = 14) endotype subgroups based on eosinophil and neutrophil levels. Objective comparisons between groups were made using measurements from forced expiratory volume in 1 second (FEV₁), fraction of exhaled nitric oxide (FeNO), immunoglobin E (IgE), high-sensitivity C-reactive protein (hsCRP), IL-6, resistin, MMP-9, plasma soluble urokinase plasminogen activator receptor (suPAR), leptin, HMW adiponectin, and periostin tests. Asthma-related medications and disease exacerbation data were collected from medical records accumulated over the 12-year study period.

The neutrophilic group was defined by high (≥ 4.4×10^9/L) neutrophil but low (< 0.30×10⁹/L) eosinophil counts and conversely the eosinophilic group had low (< 4.4×10⁹/L) neutrophil but high (≥ 0.30×10⁹/L) eosinophil counts. The paucigranulocytic was low and the mixed granulocytic group was high for both eosinophil and neutrophil levels, respectively. Each group was associated with a unique profile of features related to asthma prognosis and treatment. The paucigranulocytic endotype was used as the base comparison group in regression analysis as it was the least likely to meet the definition of severe asthma. This was indicated by the lowest use of inhaled corticosteroid (ICS), antibiotics, and occurrence of unplanned respiratory visits. The other three groups were more likely to fulfill a severe asthma classification.

Negative binomial regression analysis showed significant association of increased incidence rate ratio (IRR) of unplanned respiratory visits, highest body mass index (BMI), and highest dispensed doses of ICS with neutrophilic asthma. Additional significantly associated factors included smoking history and gender. Adjustment for dispensed ICS 2 years prior to the 12-year follow-up visit resulted in a change from borderline to significant association of increased IRR for the eosinophilic group. Both the eosinophilic and neutrophilic groups were associated with the most antibiotic use over the 12-year follow-up period. The authors suggested their data may indicate that antibiotics are overprescribed for asthma and further investigation is required.

Multiple linear regression analysis showed a decline in lung function associated with the eosinophilic but not the neutrophilic group. Connections between specific blood endotypes and molecular features were also identified. Highest periostin and FeNO levels found in the eosinophilic group were consistent with other studies on patients specifically diagnosed with eosinophilic asthma.

The neutrophilic group was distinguished by the highest hsCRP, MMP-9, IL-6, leptin, and suPAR levels. Highest resistin levels were found in both the mixed granulocyte and neutrophilic groups.

This study was strengthened by its real life long-term nature and method for cohort selection, according to the authors, though the value of a larger population to raise numbers particularly in the smaller sized groups was noted.

The authors concluded: “Our study indicates that assays of blood eosinophil and neutrophil counts provide useful information for assessing and treating patients with adult-onset asthma. These granulocyte counts reflect the underlying inflammatory pattern and reveal important differences in asthma clinical features and outcomes.” Additional research “regarding biomarkers used to identify different endotypes of asthma” is needed.

The study was sponsored by a number of research foundations in Finland as well as hospital research center funds. Several of the authors disclosed associations with pharmaceutical companies, including Astra Zeneca, Boehringer-Ingelheim, GSK, Novartis, and Sanofi.

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

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

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

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

It’s a common scenario. A patient, Agnes, with symptoms of an upper respiratory infection (URI), but what’s the cause? Is it COVID-19, flu, or even RSV? I recently described just such a patient, an obese woman with type 2 diabetes, presenting with fever, cough, myalgia, and fatigue. I asked readers whether they agreed with my management of this patient.

Thank you for your comments as we continue to react to high rates of URIs. Your comments highlight the importance of local resources and practice habits when managing patients with URI.

It was clear that readers value testing to distinguish between infections. However, access to testing is highly variable around the world and is likely to be routinely used only in high-income countries. The Kaiser Family Foundation performed a cost analysis of testing for SARS-CoV-2 in 2020 and found, not surprisingly, wide variability in the cost of testing. Medicare covers tests at rates of $36-$143 per test; a study of list prices for SARS-CoV-2 tests at 93 hospitals found a median cost of $148 per test. And this does not include collection or facility fees. About 20% of tests cost more than $300.

These costs are prohibitive for many health systems. However, more devices have been introduced since that analysis, and competition and evolving technology should drive down prices. Generally, multiplex polymerase chain reaction (PCR) testing for multiple pathogens is less expensive than ordering two or three separate molecular tests and is more convenient for patients and practices alike.

Other reader comments focused on the challenges of getting accurate data on viral epidemiology, and there is certainly a time lag between infection trends and public health reports. This is exacerbated by underreporting of symptoms and more testing at home using antigen tests.

But please do not give up on epidemiology! If a test such as PCR is 90% sensitive for identifying infection, the yield in terms of the number of individuals infected with a particular virus should be high, and that is true when infection is in broad circulation. If 20% of a population of 1,000 has an infection and the test sensitivity is 90%, the yield of testing is 180 true cases versus 20 false positives.

However, if just 2% of the population of 1,000 has the infection in this same scenario, then only 18 true cases are identified. The effect on public health is certainly less, and a lower prevalence rate means that confounding variables, such as how long an individual might shed viral particles and the method of sample collection, have an outsized effect on results. This reduces the validity of diagnostic tests.

Even trends on a national level can provide some insight regarding whom to test. Traditionally, our practice has been to not routinely test patients for influenza or RSV from late spring to early fall unless there was a compelling reason, such as recent travel to an area where these infections were more prevalent. The loss of temporality for these infections since 2020 has altered this approach and made us pay more attention to reports from public health organizations.

I also appreciate the discussion of how to treat Agnes’s symptoms as she waits to improve, and anyone who suffers with or treats a viral URI knows that there are few interventions effective for such symptoms as cough and congestion. A systematic review of 29 randomized controlled trials of over-the-counter medications for cough yielded mixed and largely negative results.

Antihistamines alone do not seem to work, and guaifenesin was successful in only one of three trials. Combinations of different drug classes appeared to be slightly more effective.

My personal favorite for the management of acute cough is something that kids generally love: honey. In a review of 14 studies, 9 of which were limited to pediatric patients, honey was associated with significant reductions in cough frequency, cough severity, and total symptom score. However, there was a moderate risk of bias in the included research, and evidence of honey’s benefit in placebo-controlled trials was limited. Honey used in this research came in a variety of forms, so the best dosage is uncertain.

Clearly, advancements are needed. Better symptom management in viral URI will almost certainly improve productivity across the population and will probably reduce the inappropriate use of antibiotics as well. I have said for years that the scientists who can solve the Gordian knot of pediatric mucus deserve three Nobel prizes. I look forward to that golden day.

Dr. Vega is a clinical professor of family medicine at the University of California, Irvine. He reported a conflict of interest with McNeil Pharmaceuticals.

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

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

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

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

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

A surgeon in Tulsa shot by a disgruntled patient. A doctor in India beaten by a group of bereaved family members. A general practitioner in the United Kingdom threatened with stabbing. The reality is grim: Health care workers across the globe experience violence while at work. A new study identifies this trend and finds that 25% of health care workers polled were willing to quit because of such violence.

“That was pretty appalling,” Rahul Kashyap, MD, MBA, MBBS, recalls. Dr. Kashyap is one of the leaders of the Violence Study of Healthcare Workers and Systems (ViSHWaS), which polled an international sample of physicians, nurses, and hospital staff. This study has worrying implications, Dr. Kashyap says. In a time when hospital staff are reporting burnout in record numbers, further deterrents may be the last thing our health care system needs. But Dr. Kashyap hopes that bringing awareness to these trends may allow physicians, policymakers, and the public to mobilize and intervene before it’s too late.

Previous studies have revealed similar trends. The rate of workplace violence directed at U.S. health care workers is five times that of workers in any other industry, according to the Bureau of Labor Statistics. The same study found that attacks had increased 63% from 2011 to 2018. Other polls that focus on the pandemic show that nearly half of U.S. nurses believe that violence increased since the world shut down. Well before the pandemic, however, a study from the Indian Medical Association found that 75% of doctors experienced workplace violence.

With this history in mind, perhaps it’s not surprising that the idea for the study came from the authors’ personal experiences. They had seen coworkers go through attacks, or they had endured attacks themselves, Dr. Kashyap says. But they couldn’t find any global data to back up these experiences. So Dr. Kashyap and his colleagues formed a web of volunteers dedicated to creating a cross-sectional study.

They got in touch with researchers from countries across Asia, the Middle East, South America, North America, and Africa. The initial group agreed to reach out to their contacts, casting a wide net. Researchers used WhatsApp, LinkedIn, and text messages to distribute the survey. Health care workers in each country completed the brief questionnaire, recalling their prepandemic world and evaluating their current one.

Within 2 months, they had reached health care workers in more than 100 countries. They concluded the study when they received about 5,000 results, according to Dr. Kashyap, and then began the process of stratifying the data. For this report, they focused on critical care, emergency medicine, and anesthesiology, which resulted in 598 responses from 69 countries. Of these, India and the United States had the highest number of participants.

In all, 73% of participants reported facing physical or verbal violence while in the hospital; 48% said they felt less motivated to work because of that violence; 39% of respondents believed that the amount of violence they experienced was the same as before the COVID-19 pandemic; and 36% of respondents believed that violence had increased. Even though they were trained on guidelines from the Occupational Safety and Health Administration, 20% of participants felt unprepared to face violence.

Although the study didn’t analyze the reasons workers felt this way, Dr. Kashyap speculates that it could be related to the medical distrust that grew during the pandemic or the stress patients and health care professionals experienced during its peak.

Regardless, the researchers say their study is a starting point. Now that the trend has been highlighted, it may be acted on.

Moving forward, Dr. Kashyap believes that controlling for different variables could determine whether factors like gender or shift time put a worker at higher risk for violence. He hopes it’s possible to interrupt these patterns and reestablish trust in the hospital environment. “It’s aspirational, but you’re hoping that through studies like ViSHWaS, which means trust in Hindi ... [we could restore] the trust and confidence among health care providers for the patients and family members.”

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

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

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

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

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

At least one state licensing agency is revoking nursing licenses allegedly obtained in a multistate fake diploma scheme.

The U.S. Department of Justice recently announced charges against 25 owners, operators, and employees of three Florida nursing schools in a fraud scheme in which they sold as many as 7,600 fake nursing degrees.

The purchasers in the diploma scheme paid $10,000 to $15,000 for degrees and transcripts and some 2,800 of the buyers passed the national nursing licensing exam to become registered nurses (RNs) and licensed practice nurses/vocational nurses (LPN/VNs) around the country, according to The New York Times.

Many of the degree recipients went on to work at hospitals, nursing homes, and Veterans Affairs medical centers, according to the U.S. Attorney’s Office for the Southern District of Florida.

Several national nursing organizations cooperated with the investigation, and the Delaware Division of Professional Regulation already annulled 26 licenses, according to the Delaware Nurses Association. Fake licenses were issued in five states, according to federal reports.

“We are deeply unsettled by this egregious act,” DNA President Stephanie McClellan, MSN, RN, CMSRN, said in the group’s press statement. “We want all Delaware nurses to be aware of this active issue and to speak up if there is a concern regarding capacity to practice safely by a colleague/peer,” she said.

The Oregon State Board of Nursing is also investigating at least a dozen nurses who may have paid for their degrees, according to a Portland CBS affiliate.

The National Council of State Boards of Nursing said in a statement that it had helped authorities identify and monitor the individuals who allegedly provided the false degrees.
 

Nursing community reacts

News of the fraud scheme spread through the nursing community, including social media. “The recent report on falsified nursing school degrees is both heartbreaking and serves as an eye-opener,” tweeted Usha Menon, PhD, RN, FAAN, dean and health professor of the University of South Florida Health College of Nursing. “There was enough of a need that prompted these bad actors to develop a scheme that could’ve endangered dozens of lives.”

Jennifer Mensik Kennedy, PhD, MBA, RN, the new president of the American Nurses Association, also weighed in. “The accusation that personnel at once-accredited nursing schools allegedly participated in this scheme is simply deplorable. These unlawful and unethical acts disparage the reputation of actual nurses everywhere who have rightfully earned [their titles] through their education, hard work, dedication, and time.”

The false degrees and transcripts were issued by three once-accredited and now-shuttered nursing schools in South Florida: Palm Beach School of Nursing, Sacred Heart International Institute, and Sienna College.

The alleged co-conspirators reportedly made $114 million from the scheme, which dates back to 2016, according to several news reports. Each defendant faces up to 20 years in prison.

Most LPN programs charge $10,000 to $15,000 to complete a program, Robert Rosseter, a spokesperson for the American Association of Colleges of Nursing (AACN), told this news organization.

None were AACN members, and none were accredited by the Commission on Collegiate Nursing Education, which is AACN’s autonomous accrediting agency, Mr. Rosseter said. AACN membership is voluntary and is open to schools offering baccalaureate or higher degrees, he explained.

“What is disturbing about this investigation is that there are over 7,600 people around the country with fraudulent nursing credentials who are potentially in critical health care roles treating patients,” Chad Yarbrough, acting special agent in charge for the FBI in Miami, said in the federal justice department release.
 

‘Operation Nightingale’ based on tip

The federal action, dubbed “Operation Nightingale” after the nursing pioneer Florence Nightingale, began in 2019. It was based on a tip related to a case in Maryland, according to Nurse.org.

That case ensnared Palm Beach School of Nursing owner Johanah Napoleon, who reportedly was selling fake degrees for $6,000 to $18,000 each to two individuals in Maryland and Virginia. Ms. Napoleon was charged in 2021 and eventually pled guilty. The Florida Board of Nursing shut down the Palm Beach school in 2017 owing to its students’ low passing rate on the national licensing exam.

Two participants in the bigger scheme who had also worked with Ms. Napoleon – Geralda Adrien and Woosvelt Predestin – were indicted in 2021. Ms. Adrien owned private education companies for people who at aspired to be nurses, and Mr. Predestin was an employee. They were sentenced to 27 months in prison last year and helped the federal officials build the larger case.

The 25 individuals who were charged Jan. 25 operated in Delaware, New York, New Jersey, Texas, and Florida.
 

Schemes lured immigrants

In the scheme involving Siena College, some of the individuals acted as recruiters to direct nurses who were looking for employment to the school, where they allegedly would then pay for an RN or LPN/VN degree. The recipients of the false documents then used them to obtain jobs, including at a hospital in Georgia and a Veterans Affairs medical center in Maryland, according to one indictment. The president of Siena and her co-conspirators sold more than 2,000 fake diplomas, according to charging documents.

At the Palm Beach College of Nursing, individuals at various nursing prep and education programs allegedly helped others obtain fake degrees and transcripts, which were then used to pass RN and LPN/VN licensing exams in states that included Massachusetts, New Jersey, New York, and Ohio, according to the indictment.

Some individuals then secured employment with a nursing home in Ohio, a home health agency for pediatric patients in Massachusetts, and skilled nursing facilities in New York and New Jersey.

Prosecutors allege that the president of Sacred Heart International Institute and two other co-conspirators sold 588 fake diplomas.

The FBI said that some of the aspiring nurses who were talked into buying the degrees were LPNs who wanted to become RNs and that most of those lured into the scheme were from South Florida’s Haitian American immigrant community, Nurse.org reported.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To paraphrase Winston Churchill, Gulf War Illness (GWI) is a mystery wrapped in an enigma—a complex interplay of multiple symptoms, caused by a variety of environmental and chemical hazards. To make things more difficult, there are no diagnostic biomarkers or objective laboratory tests with which to confirm a GWI case. Instead, clinicians rely on patients’ reports of symptoms and the absence of other explanations for the symptoms.

Looking to provide more information on the epidemiology and biology of GWI, US Department of Veterans Affairs (VA) researchers analyzed data from the VA Cooperative Studies Program 2006/Million Veteran Program 029 cohort, the largest sample of GW-era veterans available for research to date: 35,902 veterans, of whom 13,107 deployed to a post 9/11 Persian Gulf conflict.

The researchers used the Kansas (KS) and Centers for Disease Control and Prevention (CDC) definitions of GWI, both of which are based on patient self-reports. The KS GWI criteria for phenotype KS Sym+ require ≥ 2 mild symptoms or ≥ 1 moderate or severe symptoms in at least 3 of 6 domains: fatigue/sleep problems, pain, neurologic/cognitive/mood, gastrointestinal, respiratory, and skin. The criteria for phenotype KS Sym+/Dx- also exclude some diagnosed health conditions, such as cancer, diabetes mellitus, and heart disease. The researchers examined both of these phenotypes.

They also used 2 phenotypes of the CDC definition: CDC GWI is met if the veteran reports ≥ 1 symptoms in 2 of 3 domains (fatigue, musculoskeletal, and mood/cognition). The second, CDC GWI severe, is met if the veteran rates ≥ 1 symptoms as severe in ≥ 2 domains.

Of the veterans studied, 67.1% met the KS Sym+ phenotype; 21.5% met the KS Sym+/Dx– definition. A majority (81.1%) met the CDC GWI phenotype; 18.6% met the severe phenotype. The most prevalent KS GWI domains were neurologic/cognitive/mood (81.9%), fatigue/sleep problems (73.9%), and pain (71.5%).

Although their findings mainly laid a foundation for further research, the researchers pointed to some potential new avenues for exploration. For instance, “Importantly,” the researchers say, “we consistently observed that deployed relative to nondeployed veterans had higher odds of meeting each GWI phenotype.” For both deployed and nondeployed veterans, those who served in the Army or Marine Corps had higher odds of meeting the KS Sym+, CDC GWI, and CDC GWI severe phenotypes. Among the deployed, Reservists had higher odds of CDC GWI and CDC GWI severe than did active-duty veterans.

Their findings also revealed that older age was associated with lower odds of meeting the GWI phenotypes. “[S]omewhat surprisingly,” they note, this finding held in both nondeployed and deployed samples, even after adjusting for military rank during the war. The researchers cite other research that has suggested younger service members are at greater risk for GWI (because they’re more likely, for example, to be exposed to deployment-related toxins). Most studies, the researchers note, have shown GWI and related symptoms to be more common among enlisted personnel than officers. Biomarkers of aging, such as epigenetic age acceleration, they suggest, “may be useful in untangling the relationship between age and GWI case status.” 

Because they separately examined the association of demographic characteristics with the GWI phenotypes, the researchers also found that women, regardless of deployment status, had higher odds of meeting the GWI phenotypes compared with men.

Their findings will be used, the researchers say, “to understand how genetic variation is associated with the GWI phenotypes and to identify potential pathophysiologic underpinnings of GWI, pleiotropy with other traits, and gene by environment interactions.” With information from this large dataset of GW-era veterans, they will have a “powerful tool” for in-depth study of exposures and underlying genetic susceptibility to GWI—studies that could not be performed, they say, without the full description of the GWI phenotypes they have documented.

The study had several strengths, the researchers say. For example, unlike previous studies, this one had a sample size large enough to allow more representation of subpopulations, including age, sex, race, ethnicity, education, and military service. The researchers also collected data from surveys, especially data on veterans’ self-reported symptoms and other information “incompletely and infrequently documented in medical records.”

Finally, the data for the study were collected more than 27 years after the GW. It, therefore, gives an “updated, detailed description” of symptoms and conditions affecting GW-era veterans, decades after their return from service.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.

Poly-(ADP-ribose) polymerase (PARP) inhibitors have emerged as essential therapeutic agents in patients with germline BRCA1/2-mutated BC. A BRCA-like phenotype is displayed by a large subset of patients with germline BRCA1/2-wildtype BC who present with homologous recombination deficiency (HRD). The randomized phase 2 S1416 trial (Rodler et al) evaluated the efficacy of cisplatin combined with the PARP inhibitor veliparib in three cohorts of metastatic BC: mutated germline BRCA1/2, BRCA-like, and non-BRCA–like. A total of 335 patients with metastatic or recurrent triple-negative BC (TNBC) or germline BRCA1/2-mutated metastatic BC were randomly assigned (1:1) to receive cisplatin plus either veliparib or a matching placebo. The findings showed that the addition of veliparib to cisplatin significantly improved progression-free survival (PFS) in patients with BRCA-like metastatic TNBC compared with placebo (5.9 vs 4.2 months; HR 0.57; log-rank P = .01), but not in mutated germline BRCA1/2 (6.2 vs 6.4 months; P = .54) and non-BRCA–like (4.0 vs 3.0 months; P = .57) groups. No new toxicity signals were observed. These findings suggest BRCA-like TNBC might show sensitivity to PARP inhibitors and therefore these agents should be explored further in this cohort.

A recent update from the combined analysis of the SOFT and TEXT studies comparing outcomes in 4690 premenopausal women with estrogen/progesterone receptor–positive early BC (Pagani et al) showed that exemestane plus ovarian function suppression (OFS) led to a greater reduction in recurrence risk compared with tamoxifen plus OFS in premenopausal women. After a median follow-up of 13 years, results showed a 4.6% absolute improvement in 12-year disease-free survival (HR 0.79; P < .001) and a 1.8% absolute improvement in disease recurrence-free interval (HR 0.83; P = .03) with exemestane plus OFS compared with tamoxifen plus OFS. These treatment effects on recurrence began to attenuate over time, being strongest in the first 5 years with no further improvement after 10 or more years. No improvement in overall survival (OS) was noted with exemestane vs tamoxifen, although both arms had excellent survival outcomes (90.1% vs 89.1%; HR 0.93; 95% CI 0.78-1.11). It is important to note that there was a 3.3% absolute improvement in 12-year OS with exemestane plus OFS among patients with HER2-negative tumors who received chemotherapy. This OS benefit was also noted amongst patients with high-risk clinicopathologic characteristics (<35 years and those with > 2 cm or grade 3 tumors), ranging from 4.0% to 5.5% absolute improvement. In conclusion, sustained recurrence risk reductions were noted with adjuvant exemestane plus OFS compared with tamoxifen plus OFS, with the most clinically meaningful survival benefit noted for patients with higher risk tumors. Proper selection of patients who are most likely to benefit from exemestane over tamoxifen is vital to maximize the survival benefit while minimizing the burden of treatment intensification.

Findings from a retrospective study including 221 women with BC who received preoperative neoadjuvant chemotherapy (NAC) showed that the presence of metabolic syndrome (MetS) worsened survival outcomes and increased disease recurrence risk (Zhou et al). Patients were divided into MetS and non-MetS groups according to National Cholesterol Education Program Adult Treatment Panel III criteria to investigate the association between MetS and clinicopathologic characteristics, pathologic complete response (pCR), and long-term survival. The MetS group had a significantly lower likelihood of achieving pCR after NAC compared with the non-MetS group (odds ratio [OR] 0.316; P = .028), with the risk for death (OR 2.587; P = .004) and disease recurrence (OR 2.228; P = .007) being significantly higher in patients with vs without MetS. In a multivariate analysis, MetS (P = 0.028) and hormone receptors status were independent predictors of pCR after NAC in BC. These findings emphasize the importance of timely intervention of metabolic syndrome to improve outcomes in patients with BC.