Dermatology News

Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.

Marc Bruxelle/Getty Images

“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.

“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
 

Study details

The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.

In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.

Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
 

Results

The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.

Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).

In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
 

Patient age is an important consideration

Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.

“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”

Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.

”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”

The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.

”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”

Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.

“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.

”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”

The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.

Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.

Marc Bruxelle/Getty Images

“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.

“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
 

Study details

The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.

In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.

Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
 

Results

The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.

Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).

In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
 

Patient age is an important consideration

Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.

“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”

Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.

”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”

The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.

”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”

Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.

“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.

”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”

The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.

Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.

Marc Bruxelle/Getty Images

“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.

“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
 

Study details

The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.

In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.

Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
 

Results

The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.

Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).

In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
 

Patient age is an important consideration

Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.

“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”

Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.

”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”

The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.

”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”

Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.

“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.

”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”

The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.^1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.^2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.⁷ Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.³ This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.⁷

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.³

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.¹⁰

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.¹¹

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.^6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.¹³

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).^6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.⁶

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.¹⁵

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.⁹

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.¹⁶ The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.¹⁷

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.^1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.^2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.⁷ Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.³ This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.⁷

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.³

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.¹⁰

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.¹¹

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.^6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.¹³

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).^6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.⁶

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.¹⁵

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.⁹

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.¹⁶ The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.¹⁷

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.^1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.^2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.⁷ Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.³ This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.⁷

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.³

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.¹⁰

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.¹¹

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.^6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.¹³

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).^6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.⁶

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.¹⁵

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.⁹

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.¹⁶ The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.¹⁷

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Patients with psoriatic arthritis (PsA) showed more improvement in symptoms at 6 months with risankizumab (Skyrizi) than with placebo in combined phase 3, randomized, controlled trials, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“Risankizumab was well tolerated and showed no new safety signals over those seen in the trial program for psoriasis,” reported Andrew Östör, MD, of Monash University and Cabrini Hospital, both in Melbourne. The results included pooled data that added KEEPsAKE 1 data to KEEPsAKE 2 results, which were presented at the 2021 congress of the European Alliance of Associations for Rheumatology.

Risankizumab received Food and Drug Administration approval in 2019 for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The humanized monoclonal antibody inhibits interleukin-23, which is believed to be involved in the development of PsA. The FDA updated its approval in August 2021 to make it available as a 150-mg single-dose injection instead of two 75-mg doses for psoriasis treatment, but it is not yet approved for PsA.

The trials included adults with active PsA, active plaque psoriasis or nail psoriasis, and at least five swollen joints and five tender joints. All the participants had an inadequate response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), and KEEPsAKE 2 included participants who had an inadequate response or intolerance to at least one biologic therapy.

The majority of patients in both groups were taking anti-inflammatory drugs (58.8% with risankizumab vs. 62.1% with placebo) and methotrexate (60% vs. 59.1%, respectively), but a minority were taking oral glucocorticoids (18.2% with risankizumab vs. 15.6% with placebo). A small proportion in both groups were also taking a csDMARD besides methotrexate (11.9% with risankizumab vs. 11.3% with placebo).

Participants were randomly assigned to receive either 150 mg of subcutaneous risankizumab or placebo at baseline, 4 weeks, and 16 weeks with a double-blind protocol. The proportion of patients with 20% improvement in ACR response criteria (ACR 20) at 24 weeks was the primary endpoint. The trial is currently continuing with all participants receiving open-label risankizumab.

The 1,407 patients initially enrolled included 707 receiving risankizumab and 700 receiving placebo across both trials, with similar baseline demographic and disease characteristics in both groups. A total of 1,354 participants completed the 24-week assessments, including 688 receiving risankizumab and 666 receiving placebo. In an intent-to-treat analysis, 55.5% of patients receiving risankizumab and 31.3% of those receiving placebo achieved ACR 20 at week 24 (P < .001). Participants who received risankizumab also had more improvement in secondary clinical and patient-reported outcomes than did those who received placebo. A quarter (25.2%) of risankizumab patients versus 10.6% of placebo patients showed minimal disease activity, and significantly more participants receiving risankizumab than placebo saw resolution of enthesitis, dactylitis, and fatigue.

Adverse events of any kind occurred in 45.5% of risankizumab and 43.9% of placebo participants, with similar numbers of serious adverse events (3% vs. 4.4%, respectively). One death caused by urosepsis in an 81-year-old participant with dementia occurred in the risankizumab group and was determined to be unrelated to the drug.

David Karp, MD, PhD, chief of division of rheumatic diseases at the University of Texas Southwestern Medical Center in Dallas and ACR president, conducted a question-and-answer session with Dr. Östör following his presentation and asked whether a difference in responses was seen between patients who had failed biologic DMARDs. Dr. Östör said the response rates were similar independent of which previous therapies the participants had failed.

Regarding where risankizumab, as an IL-23 inhibitor, fits among the options for treating PsA, Dr. Östör said “the data speaks for itself” in terms of efficacy with arthritic, musculoskeletal manifestations and the patient-reported outcomes.

“One of the major benefits of these medications is their remarkable effect on skin with psoriasis,” Dr. Östör told Dr. Karp. Regarding axial response to the drug, Dr. Östör noted the statistically significant improvement in Bath Ankylosing Spondylitis Disease Activity Index, appearing to show a clinical benefit with spinal inflammatory disease. Radiologic data, however, are not currently available for the trials.

Dr. Karp noted the recent findings of a phase 2a trial published in the New England Journal of Medicine regarding risankizumab’s poor performance in patients with severe asthma, who experienced worsening symptoms sooner and more rapidly than did those who received placebo. It’s unclear whether any patients in the KEEPsAKE 1 or 2 trials had an asthma diagnosis, but any people with unstable, severe asthma would have been excluded from participation, Dr. Östör said.

The research was funded by AbbVie. Dr. Östör and colleagues have a range of financial ties to numerous pharmaceutical companies.

Patients with psoriatic arthritis (PsA) showed more improvement in symptoms at 6 months with risankizumab (Skyrizi) than with placebo in combined phase 3, randomized, controlled trials, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“Risankizumab was well tolerated and showed no new safety signals over those seen in the trial program for psoriasis,” reported Andrew Östör, MD, of Monash University and Cabrini Hospital, both in Melbourne. The results included pooled data that added KEEPsAKE 1 data to KEEPsAKE 2 results, which were presented at the 2021 congress of the European Alliance of Associations for Rheumatology.

Risankizumab received Food and Drug Administration approval in 2019 for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The humanized monoclonal antibody inhibits interleukin-23, which is believed to be involved in the development of PsA. The FDA updated its approval in August 2021 to make it available as a 150-mg single-dose injection instead of two 75-mg doses for psoriasis treatment, but it is not yet approved for PsA.

The trials included adults with active PsA, active plaque psoriasis or nail psoriasis, and at least five swollen joints and five tender joints. All the participants had an inadequate response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), and KEEPsAKE 2 included participants who had an inadequate response or intolerance to at least one biologic therapy.

The majority of patients in both groups were taking anti-inflammatory drugs (58.8% with risankizumab vs. 62.1% with placebo) and methotrexate (60% vs. 59.1%, respectively), but a minority were taking oral glucocorticoids (18.2% with risankizumab vs. 15.6% with placebo). A small proportion in both groups were also taking a csDMARD besides methotrexate (11.9% with risankizumab vs. 11.3% with placebo).

Participants were randomly assigned to receive either 150 mg of subcutaneous risankizumab or placebo at baseline, 4 weeks, and 16 weeks with a double-blind protocol. The proportion of patients with 20% improvement in ACR response criteria (ACR 20) at 24 weeks was the primary endpoint. The trial is currently continuing with all participants receiving open-label risankizumab.

The 1,407 patients initially enrolled included 707 receiving risankizumab and 700 receiving placebo across both trials, with similar baseline demographic and disease characteristics in both groups. A total of 1,354 participants completed the 24-week assessments, including 688 receiving risankizumab and 666 receiving placebo. In an intent-to-treat analysis, 55.5% of patients receiving risankizumab and 31.3% of those receiving placebo achieved ACR 20 at week 24 (P < .001). Participants who received risankizumab also had more improvement in secondary clinical and patient-reported outcomes than did those who received placebo. A quarter (25.2%) of risankizumab patients versus 10.6% of placebo patients showed minimal disease activity, and significantly more participants receiving risankizumab than placebo saw resolution of enthesitis, dactylitis, and fatigue.

Adverse events of any kind occurred in 45.5% of risankizumab and 43.9% of placebo participants, with similar numbers of serious adverse events (3% vs. 4.4%, respectively). One death caused by urosepsis in an 81-year-old participant with dementia occurred in the risankizumab group and was determined to be unrelated to the drug.

David Karp, MD, PhD, chief of division of rheumatic diseases at the University of Texas Southwestern Medical Center in Dallas and ACR president, conducted a question-and-answer session with Dr. Östör following his presentation and asked whether a difference in responses was seen between patients who had failed biologic DMARDs. Dr. Östör said the response rates were similar independent of which previous therapies the participants had failed.

Regarding where risankizumab, as an IL-23 inhibitor, fits among the options for treating PsA, Dr. Östör said “the data speaks for itself” in terms of efficacy with arthritic, musculoskeletal manifestations and the patient-reported outcomes.

“One of the major benefits of these medications is their remarkable effect on skin with psoriasis,” Dr. Östör told Dr. Karp. Regarding axial response to the drug, Dr. Östör noted the statistically significant improvement in Bath Ankylosing Spondylitis Disease Activity Index, appearing to show a clinical benefit with spinal inflammatory disease. Radiologic data, however, are not currently available for the trials.

Dr. Karp noted the recent findings of a phase 2a trial published in the New England Journal of Medicine regarding risankizumab’s poor performance in patients with severe asthma, who experienced worsening symptoms sooner and more rapidly than did those who received placebo. It’s unclear whether any patients in the KEEPsAKE 1 or 2 trials had an asthma diagnosis, but any people with unstable, severe asthma would have been excluded from participation, Dr. Östör said.

The research was funded by AbbVie. Dr. Östör and colleagues have a range of financial ties to numerous pharmaceutical companies.

Patients with psoriatic arthritis (PsA) showed more improvement in symptoms at 6 months with risankizumab (Skyrizi) than with placebo in combined phase 3, randomized, controlled trials, according to data presented at the virtual annual meeting of the American College of Rheumatology.

“Risankizumab was well tolerated and showed no new safety signals over those seen in the trial program for psoriasis,” reported Andrew Östör, MD, of Monash University and Cabrini Hospital, both in Melbourne. The results included pooled data that added KEEPsAKE 1 data to KEEPsAKE 2 results, which were presented at the 2021 congress of the European Alliance of Associations for Rheumatology.

Risankizumab received Food and Drug Administration approval in 2019 for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The humanized monoclonal antibody inhibits interleukin-23, which is believed to be involved in the development of PsA. The FDA updated its approval in August 2021 to make it available as a 150-mg single-dose injection instead of two 75-mg doses for psoriasis treatment, but it is not yet approved for PsA.

The trials included adults with active PsA, active plaque psoriasis or nail psoriasis, and at least five swollen joints and five tender joints. All the participants had an inadequate response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), and KEEPsAKE 2 included participants who had an inadequate response or intolerance to at least one biologic therapy.

The majority of patients in both groups were taking anti-inflammatory drugs (58.8% with risankizumab vs. 62.1% with placebo) and methotrexate (60% vs. 59.1%, respectively), but a minority were taking oral glucocorticoids (18.2% with risankizumab vs. 15.6% with placebo). A small proportion in both groups were also taking a csDMARD besides methotrexate (11.9% with risankizumab vs. 11.3% with placebo).

Participants were randomly assigned to receive either 150 mg of subcutaneous risankizumab or placebo at baseline, 4 weeks, and 16 weeks with a double-blind protocol. The proportion of patients with 20% improvement in ACR response criteria (ACR 20) at 24 weeks was the primary endpoint. The trial is currently continuing with all participants receiving open-label risankizumab.

The 1,407 patients initially enrolled included 707 receiving risankizumab and 700 receiving placebo across both trials, with similar baseline demographic and disease characteristics in both groups. A total of 1,354 participants completed the 24-week assessments, including 688 receiving risankizumab and 666 receiving placebo. In an intent-to-treat analysis, 55.5% of patients receiving risankizumab and 31.3% of those receiving placebo achieved ACR 20 at week 24 (P < .001). Participants who received risankizumab also had more improvement in secondary clinical and patient-reported outcomes than did those who received placebo. A quarter (25.2%) of risankizumab patients versus 10.6% of placebo patients showed minimal disease activity, and significantly more participants receiving risankizumab than placebo saw resolution of enthesitis, dactylitis, and fatigue.

Adverse events of any kind occurred in 45.5% of risankizumab and 43.9% of placebo participants, with similar numbers of serious adverse events (3% vs. 4.4%, respectively). One death caused by urosepsis in an 81-year-old participant with dementia occurred in the risankizumab group and was determined to be unrelated to the drug.

David Karp, MD, PhD, chief of division of rheumatic diseases at the University of Texas Southwestern Medical Center in Dallas and ACR president, conducted a question-and-answer session with Dr. Östör following his presentation and asked whether a difference in responses was seen between patients who had failed biologic DMARDs. Dr. Östör said the response rates were similar independent of which previous therapies the participants had failed.

Regarding where risankizumab, as an IL-23 inhibitor, fits among the options for treating PsA, Dr. Östör said “the data speaks for itself” in terms of efficacy with arthritic, musculoskeletal manifestations and the patient-reported outcomes.

“One of the major benefits of these medications is their remarkable effect on skin with psoriasis,” Dr. Östör told Dr. Karp. Regarding axial response to the drug, Dr. Östör noted the statistically significant improvement in Bath Ankylosing Spondylitis Disease Activity Index, appearing to show a clinical benefit with spinal inflammatory disease. Radiologic data, however, are not currently available for the trials.

Dr. Karp noted the recent findings of a phase 2a trial published in the New England Journal of Medicine regarding risankizumab’s poor performance in patients with severe asthma, who experienced worsening symptoms sooner and more rapidly than did those who received placebo. It’s unclear whether any patients in the KEEPsAKE 1 or 2 trials had an asthma diagnosis, but any people with unstable, severe asthma would have been excluded from participation, Dr. Östör said.

The research was funded by AbbVie. Dr. Östör and colleagues have a range of financial ties to numerous pharmaceutical companies.

For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.

Ziga Plahutar

Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.

“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.

“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.

“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.

After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”

When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”

Evidence base

Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).

Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.

Ancillary study

Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.

To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.

The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.

At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.

Results

At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).

In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.

There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).

Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.

Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.

“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.



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

For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.

Ziga Plahutar

Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.

“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.

“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.

“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.

After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”

When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”

Evidence base

Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).

Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.

Ancillary study

Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.

To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.

The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.

At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.

Results

At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).

In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.

There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).

Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.

Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.

“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.



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

For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.

Ziga Plahutar

Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.

“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.

“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.

“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.

After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”

When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”

Evidence base

Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).

Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.

Ancillary study

Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.

To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.

The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.

At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.

Results

At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).

In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.

There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).

Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.

Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.

“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.



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

Chemical peels are an effective and well-tolerated field treatment for actinic keratoses (AKs), according to the authors of a systematic review of five studies including 88 patients.

AKs remain an ongoing health concern because of their potential to become malignant, and chemical peels are among the recommended options for field therapy, wrote Angela J. Jiang, MD, from the department of dermatology at the Henry Ford Health System, Detroit, and colleagues. “Although most dermatologists agree on the importance of field treatment, cryotherapy still remains the standard of care for treatment of AKs,” they noted, adding that the safety and efficacy of chemical peels for AK field therapy have not been well studied.

Chemical peels offer the benefit of a single treatment for patients, which eliminates the patient compliance issue needed for successful topical therapy, the researchers said. In fact, “patients report preference for the tolerability of treatment with chemical peels and the shorter downtime, compared with other field treatments,” they added.

In the study published in Dermatologic Surgery, they reviewed data from five prospective studies on the safety and efficacy of chemical peels as AK field treatments published from 1946 to March 2020 in the National Library of Medicine’s PubMed database. Of the 151 articles on the use of chemical peels for AKs, the 5 studies met the criteria for their review.

One split-face study evaluated glycolic acid peels (published in 1998), two split-face studies evaluated a combination of Jessner’s and 35% trichloroacetic acid (TCA) peels (published in 1995 and 1997), and two randomized studies evaluated TCA peels alone (published in 2006 and 2016).

Overall, the studies showed efficacy of peels in reducing AK counts, with minimal adverse events. In the glycolic acid study, 70% glycolic acid plus 5-fluorouracil (5-FU) yielded a 91.9% mean reduction in AKs at 6 months’ follow-up. A combination of Jessner’s solution and 35% TCA showed a significant reduction in AKs at 12 and at 32 months post treatment – a 75% reduction at 12 months in one study and 78% at 32 months in the other – similar to results achieved with 5-FU.

In studies of TCA alone, 30% TCA peels were similar in AK reduction (89%) to 5-FU (83%) and carbon dioxide laser resurfacing (92%). In another TCA study, 35% TCA was less effective at AK reduction at 12 months, compared with aminolevulinic acid photodynamic therapy (ALA-PDT), but the 35% peel was applied at a more superficial level than in the study of 30% TCA, the authors wrote.

Chemical peels also demonstrated effectiveness in preventing keratinocytic carcinomas, the researchers wrote. In the 30% TCA study, the rate of keratinocyte carcinoma development was 3.75-5.25 times lower in patients treated with 30% TCA peels, compared with 5-FU and carbon dioxide laser resurfacing (CO₂) after 5 years.

Chemical peels were well tolerated overall, although side effects varied among the studies. Patients in one study reported no side effects, while patients in other studies reported transient erythema and discomfort. In the study comparing TCA with PDT treatment, PDT was associated with greater pain, erythema, and pustules, the researchers wrote; however, patients treated with 35% TCA reported scarring.

From patients’ perspectives, chemical peels were preferable because of the single application, brief downtime, and minimal adverse effects. From the provider perspective, chemical peels are a more cost-effective way to treat large surface areas for AKs, compared with 5-FU or lasers, the researchers said.

The study findings were limited by several factors including the small number of prospective studies and relatively small number of patients, they noted. “The small number of included studies is partially due to the lack of studies that performed AK counts before and after treatments,” they said. The dearth of literature on chemical peels for AKs may stem from lack of residency training on the use of peels, they added.

However, the results support the use of chemical peels as an effective option for field treatment of AKs, with the added benefits of convenience and cost-effectiveness for patients, they concluded.

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

Chemical peels are an effective and well-tolerated field treatment for actinic keratoses (AKs), according to the authors of a systematic review of five studies including 88 patients.

AKs remain an ongoing health concern because of their potential to become malignant, and chemical peels are among the recommended options for field therapy, wrote Angela J. Jiang, MD, from the department of dermatology at the Henry Ford Health System, Detroit, and colleagues. “Although most dermatologists agree on the importance of field treatment, cryotherapy still remains the standard of care for treatment of AKs,” they noted, adding that the safety and efficacy of chemical peels for AK field therapy have not been well studied.

Chemical peels offer the benefit of a single treatment for patients, which eliminates the patient compliance issue needed for successful topical therapy, the researchers said. In fact, “patients report preference for the tolerability of treatment with chemical peels and the shorter downtime, compared with other field treatments,” they added.

In the study published in Dermatologic Surgery, they reviewed data from five prospective studies on the safety and efficacy of chemical peels as AK field treatments published from 1946 to March 2020 in the National Library of Medicine’s PubMed database. Of the 151 articles on the use of chemical peels for AKs, the 5 studies met the criteria for their review.

One split-face study evaluated glycolic acid peels (published in 1998), two split-face studies evaluated a combination of Jessner’s and 35% trichloroacetic acid (TCA) peels (published in 1995 and 1997), and two randomized studies evaluated TCA peels alone (published in 2006 and 2016).

Overall, the studies showed efficacy of peels in reducing AK counts, with minimal adverse events. In the glycolic acid study, 70% glycolic acid plus 5-fluorouracil (5-FU) yielded a 91.9% mean reduction in AKs at 6 months’ follow-up. A combination of Jessner’s solution and 35% TCA showed a significant reduction in AKs at 12 and at 32 months post treatment – a 75% reduction at 12 months in one study and 78% at 32 months in the other – similar to results achieved with 5-FU.

In studies of TCA alone, 30% TCA peels were similar in AK reduction (89%) to 5-FU (83%) and carbon dioxide laser resurfacing (92%). In another TCA study, 35% TCA was less effective at AK reduction at 12 months, compared with aminolevulinic acid photodynamic therapy (ALA-PDT), but the 35% peel was applied at a more superficial level than in the study of 30% TCA, the authors wrote.

Chemical peels also demonstrated effectiveness in preventing keratinocytic carcinomas, the researchers wrote. In the 30% TCA study, the rate of keratinocyte carcinoma development was 3.75-5.25 times lower in patients treated with 30% TCA peels, compared with 5-FU and carbon dioxide laser resurfacing (CO₂) after 5 years.

Chemical peels were well tolerated overall, although side effects varied among the studies. Patients in one study reported no side effects, while patients in other studies reported transient erythema and discomfort. In the study comparing TCA with PDT treatment, PDT was associated with greater pain, erythema, and pustules, the researchers wrote; however, patients treated with 35% TCA reported scarring.

From patients’ perspectives, chemical peels were preferable because of the single application, brief downtime, and minimal adverse effects. From the provider perspective, chemical peels are a more cost-effective way to treat large surface areas for AKs, compared with 5-FU or lasers, the researchers said.

The study findings were limited by several factors including the small number of prospective studies and relatively small number of patients, they noted. “The small number of included studies is partially due to the lack of studies that performed AK counts before and after treatments,” they said. The dearth of literature on chemical peels for AKs may stem from lack of residency training on the use of peels, they added.

However, the results support the use of chemical peels as an effective option for field treatment of AKs, with the added benefits of convenience and cost-effectiveness for patients, they concluded.

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

Chemical peels are an effective and well-tolerated field treatment for actinic keratoses (AKs), according to the authors of a systematic review of five studies including 88 patients.

AKs remain an ongoing health concern because of their potential to become malignant, and chemical peels are among the recommended options for field therapy, wrote Angela J. Jiang, MD, from the department of dermatology at the Henry Ford Health System, Detroit, and colleagues. “Although most dermatologists agree on the importance of field treatment, cryotherapy still remains the standard of care for treatment of AKs,” they noted, adding that the safety and efficacy of chemical peels for AK field therapy have not been well studied.

Chemical peels offer the benefit of a single treatment for patients, which eliminates the patient compliance issue needed for successful topical therapy, the researchers said. In fact, “patients report preference for the tolerability of treatment with chemical peels and the shorter downtime, compared with other field treatments,” they added.

In the study published in Dermatologic Surgery, they reviewed data from five prospective studies on the safety and efficacy of chemical peels as AK field treatments published from 1946 to March 2020 in the National Library of Medicine’s PubMed database. Of the 151 articles on the use of chemical peels for AKs, the 5 studies met the criteria for their review.

One split-face study evaluated glycolic acid peels (published in 1998), two split-face studies evaluated a combination of Jessner’s and 35% trichloroacetic acid (TCA) peels (published in 1995 and 1997), and two randomized studies evaluated TCA peels alone (published in 2006 and 2016).

Overall, the studies showed efficacy of peels in reducing AK counts, with minimal adverse events. In the glycolic acid study, 70% glycolic acid plus 5-fluorouracil (5-FU) yielded a 91.9% mean reduction in AKs at 6 months’ follow-up. A combination of Jessner’s solution and 35% TCA showed a significant reduction in AKs at 12 and at 32 months post treatment – a 75% reduction at 12 months in one study and 78% at 32 months in the other – similar to results achieved with 5-FU.

In studies of TCA alone, 30% TCA peels were similar in AK reduction (89%) to 5-FU (83%) and carbon dioxide laser resurfacing (92%). In another TCA study, 35% TCA was less effective at AK reduction at 12 months, compared with aminolevulinic acid photodynamic therapy (ALA-PDT), but the 35% peel was applied at a more superficial level than in the study of 30% TCA, the authors wrote.

Chemical peels also demonstrated effectiveness in preventing keratinocytic carcinomas, the researchers wrote. In the 30% TCA study, the rate of keratinocyte carcinoma development was 3.75-5.25 times lower in patients treated with 30% TCA peels, compared with 5-FU and carbon dioxide laser resurfacing (CO₂) after 5 years.

Chemical peels were well tolerated overall, although side effects varied among the studies. Patients in one study reported no side effects, while patients in other studies reported transient erythema and discomfort. In the study comparing TCA with PDT treatment, PDT was associated with greater pain, erythema, and pustules, the researchers wrote; however, patients treated with 35% TCA reported scarring.

From patients’ perspectives, chemical peels were preferable because of the single application, brief downtime, and minimal adverse effects. From the provider perspective, chemical peels are a more cost-effective way to treat large surface areas for AKs, compared with 5-FU or lasers, the researchers said.

The study findings were limited by several factors including the small number of prospective studies and relatively small number of patients, they noted. “The small number of included studies is partially due to the lack of studies that performed AK counts before and after treatments,” they said. The dearth of literature on chemical peels for AKs may stem from lack of residency training on the use of peels, they added.

However, the results support the use of chemical peels as an effective option for field treatment of AKs, with the added benefits of convenience and cost-effectiveness for patients, they concluded.

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has unanimously voted to recommend universal hepatitis B (HBV) immunization in all unvaccinated adults aged 59 years or younger. The group also voted to expand recommendations for vaccinating people at risk for occupational exposure to Ebola and to recommend Jynneos, a smallpox and monkeypox vaccine, for at-risk populations.

The recommendations were approved Nov. 3.

Previously, ACIP recommended HBV vaccination for unvaccinated adults at increased risk for infection because of sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, HIV infection, and travel to areas with high to intermediate levels of HBV infection. But experts agreed a new strategy was needed, as previously falling rates of HBV have plateaued. “The past decade has illustrated that risk-based screening has got us as far as it can take us,” Mark Weng, MD, a lieutenant commander in the U.S. Public Health Service and lead of the ACIP Hepatitis Vaccine Working Group, said during the meeting.

There are 1.9 million people living with chronic HBV in the United States, with over 20,000 new acute infections every year. Rates are highest among those in their 40s and 50s, Dr. Weng noted.

The group debated whether to apply the universal recommendation to all ages, but in a close vote (eight yes, seven no), ACIP included an age cutoff of 59. The majority argued that adults 60 and older are at lower risk for infection and vaccination efforts targeting younger adults would be more effective. Those 60 and older would continue to follow the risk-based guidelines, but anyone, regardless of age, can receive the vaccine if they wish to be protected, the group added.

The CDC director as well as several professional societies need to approve the recommendation before it becomes public policy.

ACIP also voted to recommend the following:

• Adding updated recommendations to the 2022 immunization schedules for children, adolescents, and adults, including dengue vaccination for children aged 9-16 years in endemic areas and in adults over 65 and those aged 19-64 with certain chronic conditions.
• The use of Jynneos, a smallpox and monkeypox vaccine, as an alternative to ACAM2000 for those at risk for occupational exposure.
• Pre-exposure vaccination of health care personnel involved in the transport and treatment of suspected Ebola patients at special treatment centers, or lab and support staff working with or handling specimens that may contain the Ebola virus.

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has unanimously voted to recommend universal hepatitis B (HBV) immunization in all unvaccinated adults aged 59 years or younger. The group also voted to expand recommendations for vaccinating people at risk for occupational exposure to Ebola and to recommend Jynneos, a smallpox and monkeypox vaccine, for at-risk populations.

The recommendations were approved Nov. 3.

Previously, ACIP recommended HBV vaccination for unvaccinated adults at increased risk for infection because of sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, HIV infection, and travel to areas with high to intermediate levels of HBV infection. But experts agreed a new strategy was needed, as previously falling rates of HBV have plateaued. “The past decade has illustrated that risk-based screening has got us as far as it can take us,” Mark Weng, MD, a lieutenant commander in the U.S. Public Health Service and lead of the ACIP Hepatitis Vaccine Working Group, said during the meeting.

There are 1.9 million people living with chronic HBV in the United States, with over 20,000 new acute infections every year. Rates are highest among those in their 40s and 50s, Dr. Weng noted.

The group debated whether to apply the universal recommendation to all ages, but in a close vote (eight yes, seven no), ACIP included an age cutoff of 59. The majority argued that adults 60 and older are at lower risk for infection and vaccination efforts targeting younger adults would be more effective. Those 60 and older would continue to follow the risk-based guidelines, but anyone, regardless of age, can receive the vaccine if they wish to be protected, the group added.

The CDC director as well as several professional societies need to approve the recommendation before it becomes public policy.

ACIP also voted to recommend the following:

• Adding updated recommendations to the 2022 immunization schedules for children, adolescents, and adults, including dengue vaccination for children aged 9-16 years in endemic areas and in adults over 65 and those aged 19-64 with certain chronic conditions.
• The use of Jynneos, a smallpox and monkeypox vaccine, as an alternative to ACAM2000 for those at risk for occupational exposure.
• Pre-exposure vaccination of health care personnel involved in the transport and treatment of suspected Ebola patients at special treatment centers, or lab and support staff working with or handling specimens that may contain the Ebola virus.

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has unanimously voted to recommend universal hepatitis B (HBV) immunization in all unvaccinated adults aged 59 years or younger. The group also voted to expand recommendations for vaccinating people at risk for occupational exposure to Ebola and to recommend Jynneos, a smallpox and monkeypox vaccine, for at-risk populations.

The recommendations were approved Nov. 3.

Previously, ACIP recommended HBV vaccination for unvaccinated adults at increased risk for infection because of sexual exposure, percutaneous or mucosal exposure to blood, hepatitis C infection, chronic liver disease, end-stage renal disease, HIV infection, and travel to areas with high to intermediate levels of HBV infection. But experts agreed a new strategy was needed, as previously falling rates of HBV have plateaued. “The past decade has illustrated that risk-based screening has got us as far as it can take us,” Mark Weng, MD, a lieutenant commander in the U.S. Public Health Service and lead of the ACIP Hepatitis Vaccine Working Group, said during the meeting.

There are 1.9 million people living with chronic HBV in the United States, with over 20,000 new acute infections every year. Rates are highest among those in their 40s and 50s, Dr. Weng noted.

The group debated whether to apply the universal recommendation to all ages, but in a close vote (eight yes, seven no), ACIP included an age cutoff of 59. The majority argued that adults 60 and older are at lower risk for infection and vaccination efforts targeting younger adults would be more effective. Those 60 and older would continue to follow the risk-based guidelines, but anyone, regardless of age, can receive the vaccine if they wish to be protected, the group added.

The CDC director as well as several professional societies need to approve the recommendation before it becomes public policy.

ACIP also voted to recommend the following:

• Adding updated recommendations to the 2022 immunization schedules for children, adolescents, and adults, including dengue vaccination for children aged 9-16 years in endemic areas and in adults over 65 and those aged 19-64 with certain chronic conditions.
• The use of Jynneos, a smallpox and monkeypox vaccine, as an alternative to ACAM2000 for those at risk for occupational exposure.
• Pre-exposure vaccination of health care personnel involved in the transport and treatment of suspected Ebola patients at special treatment centers, or lab and support staff working with or handling specimens that may contain the Ebola virus.

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