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Previous endemic coronavirus encounters linked with long COVID
People who develop long COVID may be responding more strongly to a non–SARS-CoV-2 virus they encountered in the past than to SARS-CoV-2, a study by researchers at Harvard Medical School suggests.
Long COVID, also called postacute sequelae of COVID-19 (PASC), causes various symptoms that persist at least 4 weeks after the initial SARS-CoV-2 infection, they write in the preprint server medRxiv. Four authors explained their research into possible mechanisms of long COVID in an interview.
“Immunity to non-COVID endemic coronaviruses may play a role in who develops PASC,” co–lead author Jonathan D. Herman, MD, PhD, said. “There’s still so much more we need to understand, but it is striking that back-boosting of immune responses to coronavirus OC43 was uniquely enriched in individuals with PASC.”
“In the study, individuals with PASC preferentially generated stronger responses to previously encountered cold-causing coronaviruses,” co–senior author Galit Alter, PhD, said.
“Instead of generating strong SARS-CoV-2 immunity, they bolstered a response to a different coronavirus, potentially making their response less effective in clearing SARS-CoV-2. Surprisingly, most of the individuals had been vaccinated – and they still maintained this unusual antibody response – pointing to new therapeutic pathways to treat PASC,” Dr. Alter said.
Humoral immunity offers a clue to long-COVID origins
One-fifth of COVID-19 patients progress to long COVID, but which patients develop PASC and why are not well understood, the authors write.
“Antibodies represent powerful biomarkers that have been used for decades to diagnose disease. However, antibodies also provide a powerful source of information on previous infections. The use of antibody profiling, here, pointed to the presence of incomplete antibody responses to SARS-CoV-2 in individuals with PASC,” Dr. Alter said.
The researchers reviewed the medical records of patients in the Mass General Brigham health care system in Boston, including referrals from rheumatologists of participants diagnosed with COVID-19 outside the MGB system, starting on March 1, 2020.
They focused on patients with systemic autoimmune rheumatic diseases (SARDs) because their tendency toward inflammation and autoantibody production may make them more susceptible to PASC and enrich for specific inflammatory-driven endotypes.
All 43 participants had COVID-19 without hospital admission and SARDs. Patients treated only for fibromyalgia, osteoarthritis, mechanical back pain, gout, or pseudogout without a SARD were excluded from the study.
Overall, 79% of participants were female, 35% had rheumatoid arthritis, 19% had psoriatic arthritis, and 95% had received a COVID-19 vaccine.
The researchers used systems serology to perform comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens.
Long-COVID patients had a distinct immune response
Overall, 17 patients developed PASC and 26 did not, and in those with PASC, they found a distinct humoral immune response. Patients with PASC:
- harbored less inflamed and weaker Fc-gamma receptor–binding anti–SARS-CoV-2 antibodies;
- showed a significantly expanded and more inflamed antibody response against endemic coronavirus OC43; and
- mounted more avid IgM responses and developed expanded inflammatory OC43 S2–specific Fc-receptor–binding responses, which were linked to cross reactivity across SARS-CoV-2 and common coronaviruses.
“Strengths of the study include the detailed phenotypes of cases after COVID-19, particularly to classify PASC presence or absence, as well as the depth and breadth of antibody profiling. This allowed us to identify a humoral immune signature of PASC,” said co–senior author Jeffrey A. Sparks, MD, MMSc.
“However, the study was limited in its size to investigate different types of PASC, such as fatigue or lung symptoms, that may have biologic differences. Also, all patients in the study had a preexisting rheumatic disease,” he acknowledged.
“A substantial portion of patients with COVID-19 will develop PASC, which can have substantial impact on health and quality of life,” said co–senior author Zachary S. Wallace, MD, MS. “Given the higher risk of COVID-19 in many patients with rheumatic disease, it is important to understand the etiology of PASC in this vulnerable population, to enable future diagnostic and therapeutic advances.”
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California, San Diego, in La Jolla, who was not involved in the study, called the findings interesting even though the results will not immediately affect patient care.
“There may be a link between previous non–SARS-CoV-2 coronavirus infection and PASC,” he added. “Perhaps, by understanding why some people do and do not get PASC, we can develop treatments for the condition.
“This paper is a preprint and will need to go through peer review,” Dr. Smith said. “There are many elements that need to be scrutinized. For example, there is no definition of PASC that is universally accepted, so how did that play into this study?”
Mark Cameron, PhD, associate professor in the department of population and quantitative health sciences at Case Western Reserve University, Cleveland, called this a strong study from a strong group, although it is a preprint prior to peer review.
“In this initial study, the scientists focused on people who had rheumatic disease before getting COVID-19, knowing they are at higher risk for lasting complications and hopefully are more immunologically similar when diagnosed with long COVID – a single ‘endotype’ or group of patients with similar clinical symptoms and background,” he noted.
“Our immune system’s memory sometimes fails to effectively fight a new virus that looks too much like a virus it saw before. This ineffective immune response can set up various problems, including the poor recoveries we see in people with long COVID,” he said.
“OC43 probably emerged in the late 1800s and probably caused a pandemic of severe respiratory illness between 1889 and 1890, previously thought to be a flu,” Dr. Cameron recalled. “OC43 is still around as an endemic coronavirus, usually causing mild or moderate upper-respiratory infections.”
COVID-19 immunity is complex, and previous SARS-CoV-2 infection doesn’t guarantee we won't get COVID-19 again, especially as new variants emerge, added Dr. Cameron, who also was not involved in the study.
“This study may help us better understand the risks and possible mechanisms associated with COVID-19 and long COVID in the face of previous coronavirus infections,” he said. “It may also help guide future COVID-19 therapies and vaccines.”
The authors plan further related research.
The study received grant support and an anonymous donation. Dr. Alter, Dr. Sparks, and Dr. Wallace report financial relationships with the pharmaceutical industry. All other authors, and Dr. Davey and Dr. Cameron, report no conflicts of interest with the study. All experts commented by email.
* This story was updated 10/12/2022.
People who develop long COVID may be responding more strongly to a non–SARS-CoV-2 virus they encountered in the past than to SARS-CoV-2, a study by researchers at Harvard Medical School suggests.
Long COVID, also called postacute sequelae of COVID-19 (PASC), causes various symptoms that persist at least 4 weeks after the initial SARS-CoV-2 infection, they write in the preprint server medRxiv. Four authors explained their research into possible mechanisms of long COVID in an interview.
“Immunity to non-COVID endemic coronaviruses may play a role in who develops PASC,” co–lead author Jonathan D. Herman, MD, PhD, said. “There’s still so much more we need to understand, but it is striking that back-boosting of immune responses to coronavirus OC43 was uniquely enriched in individuals with PASC.”
“In the study, individuals with PASC preferentially generated stronger responses to previously encountered cold-causing coronaviruses,” co–senior author Galit Alter, PhD, said.
“Instead of generating strong SARS-CoV-2 immunity, they bolstered a response to a different coronavirus, potentially making their response less effective in clearing SARS-CoV-2. Surprisingly, most of the individuals had been vaccinated – and they still maintained this unusual antibody response – pointing to new therapeutic pathways to treat PASC,” Dr. Alter said.
Humoral immunity offers a clue to long-COVID origins
One-fifth of COVID-19 patients progress to long COVID, but which patients develop PASC and why are not well understood, the authors write.
“Antibodies represent powerful biomarkers that have been used for decades to diagnose disease. However, antibodies also provide a powerful source of information on previous infections. The use of antibody profiling, here, pointed to the presence of incomplete antibody responses to SARS-CoV-2 in individuals with PASC,” Dr. Alter said.
The researchers reviewed the medical records of patients in the Mass General Brigham health care system in Boston, including referrals from rheumatologists of participants diagnosed with COVID-19 outside the MGB system, starting on March 1, 2020.
They focused on patients with systemic autoimmune rheumatic diseases (SARDs) because their tendency toward inflammation and autoantibody production may make them more susceptible to PASC and enrich for specific inflammatory-driven endotypes.
All 43 participants had COVID-19 without hospital admission and SARDs. Patients treated only for fibromyalgia, osteoarthritis, mechanical back pain, gout, or pseudogout without a SARD were excluded from the study.
Overall, 79% of participants were female, 35% had rheumatoid arthritis, 19% had psoriatic arthritis, and 95% had received a COVID-19 vaccine.
The researchers used systems serology to perform comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens.
Long-COVID patients had a distinct immune response
Overall, 17 patients developed PASC and 26 did not, and in those with PASC, they found a distinct humoral immune response. Patients with PASC:
- harbored less inflamed and weaker Fc-gamma receptor–binding anti–SARS-CoV-2 antibodies;
- showed a significantly expanded and more inflamed antibody response against endemic coronavirus OC43; and
- mounted more avid IgM responses and developed expanded inflammatory OC43 S2–specific Fc-receptor–binding responses, which were linked to cross reactivity across SARS-CoV-2 and common coronaviruses.
“Strengths of the study include the detailed phenotypes of cases after COVID-19, particularly to classify PASC presence or absence, as well as the depth and breadth of antibody profiling. This allowed us to identify a humoral immune signature of PASC,” said co–senior author Jeffrey A. Sparks, MD, MMSc.
“However, the study was limited in its size to investigate different types of PASC, such as fatigue or lung symptoms, that may have biologic differences. Also, all patients in the study had a preexisting rheumatic disease,” he acknowledged.
“A substantial portion of patients with COVID-19 will develop PASC, which can have substantial impact on health and quality of life,” said co–senior author Zachary S. Wallace, MD, MS. “Given the higher risk of COVID-19 in many patients with rheumatic disease, it is important to understand the etiology of PASC in this vulnerable population, to enable future diagnostic and therapeutic advances.”
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California, San Diego, in La Jolla, who was not involved in the study, called the findings interesting even though the results will not immediately affect patient care.
“There may be a link between previous non–SARS-CoV-2 coronavirus infection and PASC,” he added. “Perhaps, by understanding why some people do and do not get PASC, we can develop treatments for the condition.
“This paper is a preprint and will need to go through peer review,” Dr. Smith said. “There are many elements that need to be scrutinized. For example, there is no definition of PASC that is universally accepted, so how did that play into this study?”
Mark Cameron, PhD, associate professor in the department of population and quantitative health sciences at Case Western Reserve University, Cleveland, called this a strong study from a strong group, although it is a preprint prior to peer review.
“In this initial study, the scientists focused on people who had rheumatic disease before getting COVID-19, knowing they are at higher risk for lasting complications and hopefully are more immunologically similar when diagnosed with long COVID – a single ‘endotype’ or group of patients with similar clinical symptoms and background,” he noted.
“Our immune system’s memory sometimes fails to effectively fight a new virus that looks too much like a virus it saw before. This ineffective immune response can set up various problems, including the poor recoveries we see in people with long COVID,” he said.
“OC43 probably emerged in the late 1800s and probably caused a pandemic of severe respiratory illness between 1889 and 1890, previously thought to be a flu,” Dr. Cameron recalled. “OC43 is still around as an endemic coronavirus, usually causing mild or moderate upper-respiratory infections.”
COVID-19 immunity is complex, and previous SARS-CoV-2 infection doesn’t guarantee we won't get COVID-19 again, especially as new variants emerge, added Dr. Cameron, who also was not involved in the study.
“This study may help us better understand the risks and possible mechanisms associated with COVID-19 and long COVID in the face of previous coronavirus infections,” he said. “It may also help guide future COVID-19 therapies and vaccines.”
The authors plan further related research.
The study received grant support and an anonymous donation. Dr. Alter, Dr. Sparks, and Dr. Wallace report financial relationships with the pharmaceutical industry. All other authors, and Dr. Davey and Dr. Cameron, report no conflicts of interest with the study. All experts commented by email.
* This story was updated 10/12/2022.
People who develop long COVID may be responding more strongly to a non–SARS-CoV-2 virus they encountered in the past than to SARS-CoV-2, a study by researchers at Harvard Medical School suggests.
Long COVID, also called postacute sequelae of COVID-19 (PASC), causes various symptoms that persist at least 4 weeks after the initial SARS-CoV-2 infection, they write in the preprint server medRxiv. Four authors explained their research into possible mechanisms of long COVID in an interview.
“Immunity to non-COVID endemic coronaviruses may play a role in who develops PASC,” co–lead author Jonathan D. Herman, MD, PhD, said. “There’s still so much more we need to understand, but it is striking that back-boosting of immune responses to coronavirus OC43 was uniquely enriched in individuals with PASC.”
“In the study, individuals with PASC preferentially generated stronger responses to previously encountered cold-causing coronaviruses,” co–senior author Galit Alter, PhD, said.
“Instead of generating strong SARS-CoV-2 immunity, they bolstered a response to a different coronavirus, potentially making their response less effective in clearing SARS-CoV-2. Surprisingly, most of the individuals had been vaccinated – and they still maintained this unusual antibody response – pointing to new therapeutic pathways to treat PASC,” Dr. Alter said.
Humoral immunity offers a clue to long-COVID origins
One-fifth of COVID-19 patients progress to long COVID, but which patients develop PASC and why are not well understood, the authors write.
“Antibodies represent powerful biomarkers that have been used for decades to diagnose disease. However, antibodies also provide a powerful source of information on previous infections. The use of antibody profiling, here, pointed to the presence of incomplete antibody responses to SARS-CoV-2 in individuals with PASC,” Dr. Alter said.
The researchers reviewed the medical records of patients in the Mass General Brigham health care system in Boston, including referrals from rheumatologists of participants diagnosed with COVID-19 outside the MGB system, starting on March 1, 2020.
They focused on patients with systemic autoimmune rheumatic diseases (SARDs) because their tendency toward inflammation and autoantibody production may make them more susceptible to PASC and enrich for specific inflammatory-driven endotypes.
All 43 participants had COVID-19 without hospital admission and SARDs. Patients treated only for fibromyalgia, osteoarthritis, mechanical back pain, gout, or pseudogout without a SARD were excluded from the study.
Overall, 79% of participants were female, 35% had rheumatoid arthritis, 19% had psoriatic arthritis, and 95% had received a COVID-19 vaccine.
The researchers used systems serology to perform comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens.
Long-COVID patients had a distinct immune response
Overall, 17 patients developed PASC and 26 did not, and in those with PASC, they found a distinct humoral immune response. Patients with PASC:
- harbored less inflamed and weaker Fc-gamma receptor–binding anti–SARS-CoV-2 antibodies;
- showed a significantly expanded and more inflamed antibody response against endemic coronavirus OC43; and
- mounted more avid IgM responses and developed expanded inflammatory OC43 S2–specific Fc-receptor–binding responses, which were linked to cross reactivity across SARS-CoV-2 and common coronaviruses.
“Strengths of the study include the detailed phenotypes of cases after COVID-19, particularly to classify PASC presence or absence, as well as the depth and breadth of antibody profiling. This allowed us to identify a humoral immune signature of PASC,” said co–senior author Jeffrey A. Sparks, MD, MMSc.
“However, the study was limited in its size to investigate different types of PASC, such as fatigue or lung symptoms, that may have biologic differences. Also, all patients in the study had a preexisting rheumatic disease,” he acknowledged.
“A substantial portion of patients with COVID-19 will develop PASC, which can have substantial impact on health and quality of life,” said co–senior author Zachary S. Wallace, MD, MS. “Given the higher risk of COVID-19 in many patients with rheumatic disease, it is important to understand the etiology of PASC in this vulnerable population, to enable future diagnostic and therapeutic advances.”
Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California, San Diego, in La Jolla, who was not involved in the study, called the findings interesting even though the results will not immediately affect patient care.
“There may be a link between previous non–SARS-CoV-2 coronavirus infection and PASC,” he added. “Perhaps, by understanding why some people do and do not get PASC, we can develop treatments for the condition.
“This paper is a preprint and will need to go through peer review,” Dr. Smith said. “There are many elements that need to be scrutinized. For example, there is no definition of PASC that is universally accepted, so how did that play into this study?”
Mark Cameron, PhD, associate professor in the department of population and quantitative health sciences at Case Western Reserve University, Cleveland, called this a strong study from a strong group, although it is a preprint prior to peer review.
“In this initial study, the scientists focused on people who had rheumatic disease before getting COVID-19, knowing they are at higher risk for lasting complications and hopefully are more immunologically similar when diagnosed with long COVID – a single ‘endotype’ or group of patients with similar clinical symptoms and background,” he noted.
“Our immune system’s memory sometimes fails to effectively fight a new virus that looks too much like a virus it saw before. This ineffective immune response can set up various problems, including the poor recoveries we see in people with long COVID,” he said.
“OC43 probably emerged in the late 1800s and probably caused a pandemic of severe respiratory illness between 1889 and 1890, previously thought to be a flu,” Dr. Cameron recalled. “OC43 is still around as an endemic coronavirus, usually causing mild or moderate upper-respiratory infections.”
COVID-19 immunity is complex, and previous SARS-CoV-2 infection doesn’t guarantee we won't get COVID-19 again, especially as new variants emerge, added Dr. Cameron, who also was not involved in the study.
“This study may help us better understand the risks and possible mechanisms associated with COVID-19 and long COVID in the face of previous coronavirus infections,” he said. “It may also help guide future COVID-19 therapies and vaccines.”
The authors plan further related research.
The study received grant support and an anonymous donation. Dr. Alter, Dr. Sparks, and Dr. Wallace report financial relationships with the pharmaceutical industry. All other authors, and Dr. Davey and Dr. Cameron, report no conflicts of interest with the study. All experts commented by email.
* This story was updated 10/12/2022.
FROM MEDRXIV
HPV infection in pregnancy higher among women living with HIV
Pregnant women living with HIV were more likely to be infected with human papillomavirus (HPV) than were pregnant women without HIV, a recent systematic review and meta-analysis reports.
“High prevalence of HPV was documented in pregnant WLWH [women living with HIV], exceeding the prevalence among pregnant women without HIV,” Elisabeth McClymont, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in the Journal of Acquired Immune Deficiency Syndrome.
Their results contribute to two major global public health goals: eliminating cervical cancer and improving the health outcomes of newborn babies.
“Our findings of a high prevalence of HPV infection during pregnancy in WLWH, particularly of highly oncogenic HPV types, emphasize the need for HPV screening and vaccination in WLWH,” they added. “WLWH are a key population for both HPV and adverse pregnancy outcome prevention.”
Emerging evidence suggests that being infected with HPV during pregnancy may be linked with adverse pregnancy outcomes. Although women living with HIV have higher rates of HPV infection and adverse pregnancy outcomes, no prior reviews have reported on HPV infection during pregnancy in women living with HIV, the authors explained.
A study of studies
Dr. McClymont and colleagues searched the standard medical research databases through Jan. 18, 2022, for pooled and type-specific HPV prevalence and associated pregnancy outcomes among pregnant women living with HIV, including available within-study comparators of women without HIV.
They performed subgroup analyses according to polymerase chain reaction primers used to detect HPV type and according to region (Africa, Asia and Europe, the Americas).
Their analysis of 10 studies describing HPV prevalence in 1,594 pregnant women living with HIV found:
- The pooled HPV prevalence in pregnant women living with HIV was 75.5% (95% confidence interval, 50.2%-90.4%) but ranged from 23% to 98% between individual studies.
- Among the five studies that also analyzed HPV prevalence in pregnant women without HIV, the pooled prevalence was 48.1% (95% CI, 27.1%-69.8%).
- Pregnant women living with HIV had 54% higher odds of being HPV positive than did pregnant women without HIV.
- HPV-16 was the most common HPV type detected in pregnant women living with HIV, followed by HPV-52; other common types included HPV-18 and HPV-58.
- One study provided data on pregnancy outcomes in women living with HIV but did not correlate pregnancy outcomes with HPV status.
Experts urge HPV, cervical cancer screening for women living with HIV
“HPV is a common virus that can lead to cervical dysplasia and cervical cancer,” cautioned Clara Paik, MD, professor and clinic medical director of obstetrics and gynecology at UC Davis Health, Sacramento.
“HPV can also be associated with adverse pregnancy outcomes, including preterm birth and premature membrane rupture,” she said in an interview. “It is important to know the prevalence of HPV infection in pregnant women living with HIV in order to assess if this specific population is at higher risk for adverse pregnancy outcomes.”
Dr. Paik, who was not involved in the study, would like these results to lead to better HPV screening in pregnant women living with HIV.
“The study’s strengths include the large number of women studied when all the research studies were pooled,” she said. “A weakness is that, if individual studies had limitations, a systematic review based on weaker studies may not necessarily yield results that are conclusive.”
Linda Eckert, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, said that the study highlights the importance of including cervical cancer screening in antepartum care, especially in areas of high HIV prevalence.
“Women living with HIV have a sixfold increased rate of developing cervical cancer compared to women without HIV,” she added, citing a 2020 analysis in The Lancet Global Health that estimated global cervical cancer risk among women living with HIV.
“This [new] study allows us to definitively say that pregnant women living with HIV have higher rates of HPV than do pregnant women without HIV,” noted Dr. Eckert, who was not involved in either study. “And HPV type 16 – the HPV type most associated with developing cervical cancer – was the most common high-risk HPV type found in these patients.”
HPV vaccination recommended
The World Health Organization’s call to eliminate cervical cancer has generated interest and funding for cervical cancer screening of women with HIV, Dr. Eckert said. “WHO recommends that women living with HIV who are 25 years of age and above be screened for cervical cancer annually.”
The authors urged that women living with HIV not only be screened for HPV but that they also be vaccinated against HPV.
“We know that HPV vaccination is unprecedented in its ability to prevent HPV infections when it is received prior to acquiring HPV infection,” Dr. Eckert said, “but currently data showing that HPV vaccination would treat HPV16 in pregnant women already infected with HPV16 are lacking.
“This study points to the need for a trial to investigate HPV vaccination in pregnant women living with HIV who have the high-risk HPV types,” she suggested.
Dr. Eckert contributed to the American College of Obstetricians and Gynecologists’ 2020 Human Papillomavirus Vaccination Committee Opinion. One study coauthor reported financial relationships with Merck. Dr. McClymont, the other coauthors, as well as Dr. Paik and Dr. Eckert reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pregnant women living with HIV were more likely to be infected with human papillomavirus (HPV) than were pregnant women without HIV, a recent systematic review and meta-analysis reports.
“High prevalence of HPV was documented in pregnant WLWH [women living with HIV], exceeding the prevalence among pregnant women without HIV,” Elisabeth McClymont, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in the Journal of Acquired Immune Deficiency Syndrome.
Their results contribute to two major global public health goals: eliminating cervical cancer and improving the health outcomes of newborn babies.
“Our findings of a high prevalence of HPV infection during pregnancy in WLWH, particularly of highly oncogenic HPV types, emphasize the need for HPV screening and vaccination in WLWH,” they added. “WLWH are a key population for both HPV and adverse pregnancy outcome prevention.”
Emerging evidence suggests that being infected with HPV during pregnancy may be linked with adverse pregnancy outcomes. Although women living with HIV have higher rates of HPV infection and adverse pregnancy outcomes, no prior reviews have reported on HPV infection during pregnancy in women living with HIV, the authors explained.
A study of studies
Dr. McClymont and colleagues searched the standard medical research databases through Jan. 18, 2022, for pooled and type-specific HPV prevalence and associated pregnancy outcomes among pregnant women living with HIV, including available within-study comparators of women without HIV.
They performed subgroup analyses according to polymerase chain reaction primers used to detect HPV type and according to region (Africa, Asia and Europe, the Americas).
Their analysis of 10 studies describing HPV prevalence in 1,594 pregnant women living with HIV found:
- The pooled HPV prevalence in pregnant women living with HIV was 75.5% (95% confidence interval, 50.2%-90.4%) but ranged from 23% to 98% between individual studies.
- Among the five studies that also analyzed HPV prevalence in pregnant women without HIV, the pooled prevalence was 48.1% (95% CI, 27.1%-69.8%).
- Pregnant women living with HIV had 54% higher odds of being HPV positive than did pregnant women without HIV.
- HPV-16 was the most common HPV type detected in pregnant women living with HIV, followed by HPV-52; other common types included HPV-18 and HPV-58.
- One study provided data on pregnancy outcomes in women living with HIV but did not correlate pregnancy outcomes with HPV status.
Experts urge HPV, cervical cancer screening for women living with HIV
“HPV is a common virus that can lead to cervical dysplasia and cervical cancer,” cautioned Clara Paik, MD, professor and clinic medical director of obstetrics and gynecology at UC Davis Health, Sacramento.
“HPV can also be associated with adverse pregnancy outcomes, including preterm birth and premature membrane rupture,” she said in an interview. “It is important to know the prevalence of HPV infection in pregnant women living with HIV in order to assess if this specific population is at higher risk for adverse pregnancy outcomes.”
Dr. Paik, who was not involved in the study, would like these results to lead to better HPV screening in pregnant women living with HIV.
“The study’s strengths include the large number of women studied when all the research studies were pooled,” she said. “A weakness is that, if individual studies had limitations, a systematic review based on weaker studies may not necessarily yield results that are conclusive.”
Linda Eckert, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, said that the study highlights the importance of including cervical cancer screening in antepartum care, especially in areas of high HIV prevalence.
“Women living with HIV have a sixfold increased rate of developing cervical cancer compared to women without HIV,” she added, citing a 2020 analysis in The Lancet Global Health that estimated global cervical cancer risk among women living with HIV.
“This [new] study allows us to definitively say that pregnant women living with HIV have higher rates of HPV than do pregnant women without HIV,” noted Dr. Eckert, who was not involved in either study. “And HPV type 16 – the HPV type most associated with developing cervical cancer – was the most common high-risk HPV type found in these patients.”
HPV vaccination recommended
The World Health Organization’s call to eliminate cervical cancer has generated interest and funding for cervical cancer screening of women with HIV, Dr. Eckert said. “WHO recommends that women living with HIV who are 25 years of age and above be screened for cervical cancer annually.”
The authors urged that women living with HIV not only be screened for HPV but that they also be vaccinated against HPV.
“We know that HPV vaccination is unprecedented in its ability to prevent HPV infections when it is received prior to acquiring HPV infection,” Dr. Eckert said, “but currently data showing that HPV vaccination would treat HPV16 in pregnant women already infected with HPV16 are lacking.
“This study points to the need for a trial to investigate HPV vaccination in pregnant women living with HIV who have the high-risk HPV types,” she suggested.
Dr. Eckert contributed to the American College of Obstetricians and Gynecologists’ 2020 Human Papillomavirus Vaccination Committee Opinion. One study coauthor reported financial relationships with Merck. Dr. McClymont, the other coauthors, as well as Dr. Paik and Dr. Eckert reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pregnant women living with HIV were more likely to be infected with human papillomavirus (HPV) than were pregnant women without HIV, a recent systematic review and meta-analysis reports.
“High prevalence of HPV was documented in pregnant WLWH [women living with HIV], exceeding the prevalence among pregnant women without HIV,” Elisabeth McClymont, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in the Journal of Acquired Immune Deficiency Syndrome.
Their results contribute to two major global public health goals: eliminating cervical cancer and improving the health outcomes of newborn babies.
“Our findings of a high prevalence of HPV infection during pregnancy in WLWH, particularly of highly oncogenic HPV types, emphasize the need for HPV screening and vaccination in WLWH,” they added. “WLWH are a key population for both HPV and adverse pregnancy outcome prevention.”
Emerging evidence suggests that being infected with HPV during pregnancy may be linked with adverse pregnancy outcomes. Although women living with HIV have higher rates of HPV infection and adverse pregnancy outcomes, no prior reviews have reported on HPV infection during pregnancy in women living with HIV, the authors explained.
A study of studies
Dr. McClymont and colleagues searched the standard medical research databases through Jan. 18, 2022, for pooled and type-specific HPV prevalence and associated pregnancy outcomes among pregnant women living with HIV, including available within-study comparators of women without HIV.
They performed subgroup analyses according to polymerase chain reaction primers used to detect HPV type and according to region (Africa, Asia and Europe, the Americas).
Their analysis of 10 studies describing HPV prevalence in 1,594 pregnant women living with HIV found:
- The pooled HPV prevalence in pregnant women living with HIV was 75.5% (95% confidence interval, 50.2%-90.4%) but ranged from 23% to 98% between individual studies.
- Among the five studies that also analyzed HPV prevalence in pregnant women without HIV, the pooled prevalence was 48.1% (95% CI, 27.1%-69.8%).
- Pregnant women living with HIV had 54% higher odds of being HPV positive than did pregnant women without HIV.
- HPV-16 was the most common HPV type detected in pregnant women living with HIV, followed by HPV-52; other common types included HPV-18 and HPV-58.
- One study provided data on pregnancy outcomes in women living with HIV but did not correlate pregnancy outcomes with HPV status.
Experts urge HPV, cervical cancer screening for women living with HIV
“HPV is a common virus that can lead to cervical dysplasia and cervical cancer,” cautioned Clara Paik, MD, professor and clinic medical director of obstetrics and gynecology at UC Davis Health, Sacramento.
“HPV can also be associated with adverse pregnancy outcomes, including preterm birth and premature membrane rupture,” she said in an interview. “It is important to know the prevalence of HPV infection in pregnant women living with HIV in order to assess if this specific population is at higher risk for adverse pregnancy outcomes.”
Dr. Paik, who was not involved in the study, would like these results to lead to better HPV screening in pregnant women living with HIV.
“The study’s strengths include the large number of women studied when all the research studies were pooled,” she said. “A weakness is that, if individual studies had limitations, a systematic review based on weaker studies may not necessarily yield results that are conclusive.”
Linda Eckert, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, said that the study highlights the importance of including cervical cancer screening in antepartum care, especially in areas of high HIV prevalence.
“Women living with HIV have a sixfold increased rate of developing cervical cancer compared to women without HIV,” she added, citing a 2020 analysis in The Lancet Global Health that estimated global cervical cancer risk among women living with HIV.
“This [new] study allows us to definitively say that pregnant women living with HIV have higher rates of HPV than do pregnant women without HIV,” noted Dr. Eckert, who was not involved in either study. “And HPV type 16 – the HPV type most associated with developing cervical cancer – was the most common high-risk HPV type found in these patients.”
HPV vaccination recommended
The World Health Organization’s call to eliminate cervical cancer has generated interest and funding for cervical cancer screening of women with HIV, Dr. Eckert said. “WHO recommends that women living with HIV who are 25 years of age and above be screened for cervical cancer annually.”
The authors urged that women living with HIV not only be screened for HPV but that they also be vaccinated against HPV.
“We know that HPV vaccination is unprecedented in its ability to prevent HPV infections when it is received prior to acquiring HPV infection,” Dr. Eckert said, “but currently data showing that HPV vaccination would treat HPV16 in pregnant women already infected with HPV16 are lacking.
“This study points to the need for a trial to investigate HPV vaccination in pregnant women living with HIV who have the high-risk HPV types,” she suggested.
Dr. Eckert contributed to the American College of Obstetricians and Gynecologists’ 2020 Human Papillomavirus Vaccination Committee Opinion. One study coauthor reported financial relationships with Merck. Dr. McClymont, the other coauthors, as well as Dr. Paik and Dr. Eckert reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROME.
Childhood peanut allergy linked with other legume allergies
, a retrospective study reports.
“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” senior study author Amandine Divaret-Chauveau, MD, of the Centre Hospitalier Universitaire de Nancy in Vandoeuvre-les-Nancy, France, and colleagues reported in Pediatric Allergy and Immunology.
People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.
Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.
Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one nonpeanut legume; 69.7% were boys.
The researchers analyzed data on consumption history, skin-prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:
Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
Of the 118 children also having a nonlegume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
50% of allergic reactions to nonpeanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.
Allergy awareness needs to grow with plant-based diets
“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.
Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City (Mo.), said in an interview that few data are available in the literature regarding allergies to legumes other than peanut.
“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Dr. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”
Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.
“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said in a comment.
“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.
“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.
“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.
The authors recommend further research and registry data collection of legume anaphylaxis.
Details regarding funding for the study were not provided. The authors, Dr. Shroba, and Dr. Albright report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a retrospective study reports.
“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” senior study author Amandine Divaret-Chauveau, MD, of the Centre Hospitalier Universitaire de Nancy in Vandoeuvre-les-Nancy, France, and colleagues reported in Pediatric Allergy and Immunology.
People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.
Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.
Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one nonpeanut legume; 69.7% were boys.
The researchers analyzed data on consumption history, skin-prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:
Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
Of the 118 children also having a nonlegume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
50% of allergic reactions to nonpeanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.
Allergy awareness needs to grow with plant-based diets
“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.
Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City (Mo.), said in an interview that few data are available in the literature regarding allergies to legumes other than peanut.
“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Dr. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”
Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.
“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said in a comment.
“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.
“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.
“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.
The authors recommend further research and registry data collection of legume anaphylaxis.
Details regarding funding for the study were not provided. The authors, Dr. Shroba, and Dr. Albright report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a retrospective study reports.
“Among children allergic to peanut, at least two-thirds were sensitized to one other legume, and legume allergy was diagnosed in one-quarter of the sensitized patients,” senior study author Amandine Divaret-Chauveau, MD, of the Centre Hospitalier Universitaire de Nancy in Vandoeuvre-les-Nancy, France, and colleagues reported in Pediatric Allergy and Immunology.
People worldwide are eating more legumes these days, the authors noted. High in protein, low in unsaturated fats, with low production costs, legumes are important components of increasingly vegetarian, healthy, sustainable diets.
Food allergens are the most common childhood triggers of allergic reactions. Among children in France, legumes cause 14.6% of food-related anaphylactic reactions, with peanut as the main allergen, they added.
Dr. Divaret-Chauveau and colleagues assessed the prevalence and relevance of sensitization to legumes among all children and adolescents aged 1-17 years who had peanut allergy and had been admitted to one academic pediatric allergy department over roughly 3 years, beginning in early 2017. For the 195 study participants, peanut allergy had been confirmed, and they had been documented to have consumed or to have sensitization to at least one nonpeanut legume; 69.7% were boys.
The researchers analyzed data on consumption history, skin-prick tests, specific immunoglobulin E status, prior allergic reactions, and oral food challenges for each legume. They found the following:
Among the 195 children with peanut allergy, 98.4% had at least one other atopic disease.
Of the 195 children with peanut allergy, 122 (63.9%) were sensitized to at least one other legume. Of these 122 children, 66.3% were sensitized to fenugreek, 42.2% to lentil, 39.9% to soy, and 34.2% to lupin.
Allergy to one or more legumes was confirmed for 27.9% of the 122 sensitized children, including 4.9% who had multiple legume allergies. Lentil, lupin, and pea were the main allergens.
Of the 118 children also having a nonlegume food allergy, the main food allergens were egg (57.6%), cow’s milk (33.0%), cashew (39.0%), pistachio (23.7%), and hazelnut (30.5%).
50% of allergic reactions to nonpeanut legumes were severe, often showing as asthma. Atopic comorbidities, including asthma, in most participants may have contributed to the severity of allergic reactions, the authors noted.
Allergy awareness needs to grow with plant-based diets
“The high prevalence of legume sensitization reported in our study highlights the need to explore legume consumption in children with PA [peanut allergy], and the need to investigate sensitization in the absence of consumption,” they added.
Jodi A. Shroba, MSN, APRN, CPNP, coordinator for the Food Allergy Program at Children’s Mercy Kansas City (Mo.), said in an interview that few data are available in the literature regarding allergies to legumes other than peanut.
“It was interesting that these authors found such a high legume sensitization in their peanut-allergic patients,” Dr. Shroba, who was not involved in the study, said by email. “As more people are starting to eat plant-based diets, it is important that we better understand their allergenicity and cross-reactivity so we can better help guide patient management and education.”
Deborah Albright, MD, assistant professor of pediatrics at the University of Pittsburgh, agreed.
“As plant-based protein consumption broadens worldwide, awareness of the potential for cross-reactivity and co-allergy amongst legumes will become increasingly important,” she said in a comment.
“However, positive allergy tests do not reliably correlate with true food allergy; therefore, the diagnosis of legume co-allergy should be confirmed by the individual patient’s history, a formal food challenge, or both,” advised Dr. Albright. She was not involved in the study.
“Cross-sensitization to other legumes in patients with a single legume allergy is common; however, true clinical reactivity is often not present,” she added. “Also, legume allergy test sensitization rates and objective reactivity on food challenge can vary by region, depending on diet and pollen aeroallergen exposure.
“Systematic exploration of tolerance versus co-allergy to other legumes should be considered in patients allergic to peanut or other legumes,” Dr. Albright said.
The authors recommend further research and registry data collection of legume anaphylaxis.
Details regarding funding for the study were not provided. The authors, Dr. Shroba, and Dr. Albright report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PEDIATRIC ALLERGY AND IMMUNOLOGY
USPSTF: Screen at-risk, nonpregnant people for syphilis
People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.
“Using a reaffirmation process, the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.
Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.
To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.
Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:
Assess risk:
- Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
- Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.
Screen and confirm by testing:
- Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
- Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.
Consider screening interval:
- Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.
The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.
They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
More testing, treatment, and research are needed
Four experts welcomed the reaffirmation.
“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.
“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.
Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.
“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.
Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs.
“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”
Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.
“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”
Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.
“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.
In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”
“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.
The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.
A version of this article first appeared on Medscape.com.
People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.
“Using a reaffirmation process, the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.
Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.
To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.
Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:
Assess risk:
- Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
- Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.
Screen and confirm by testing:
- Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
- Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.
Consider screening interval:
- Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.
The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.
They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
More testing, treatment, and research are needed
Four experts welcomed the reaffirmation.
“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.
“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.
Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.
“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.
Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs.
“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”
Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.
“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”
Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.
“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.
In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”
“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.
The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.
A version of this article first appeared on Medscape.com.
People at increased risk for syphilis – including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease – should be screened for it, according to a reaffirmation by the United States Preventive Services Task Force of its 2016 recommendation of syphilis screening for people at increased risk for infection.
“Using a reaffirmation process, the authors, led by Carol M. Mangione, MD, MSPH, of the University of California, Los Angeles, wrote in JAMA.
Reported cases in the United States of primary and secondary syphilis – a sexually transmitted infection caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated – increased from a low of 2.1 cases per 100,000 people in 2000 and 2001 to 11.9 cases per 100,000 in 2019, the authors reported. In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.
To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, Michelle L. Henninger, PhD, Sarah I. Bean, MPH, and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Ore., noted in a related evidence report of the post-2016 recommendation data.
Reaffirming its 2016 recommendation, the USPSTF now advises clinicians to:
Assess risk:
- Clinicians should know how common syphilis is in their community and assess their patient’s individual risk.
- Risk for syphilis is higher in MSM, people with HIV infection or other STIs, and those who use illicit drugs or have a history of incarceration, sex work, or military service.
Screen and confirm by testing:
- Traditional screening algorithm: Start with a nontreponemal test such as Venereal Disease Research Laborator or rapid plasma reagin. If positive, confirm result with a treponemal antibody detection test, such as T. pallidum particle agglutination.
- Reverse sequence algorithm: Screen with an initial automated treponemal test such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test.
Consider screening interval:
- Evidence on optimal screening intervals is limited for the general population, but MSM and people with HIV may benefit from screening yearly or every 3-6 months if they remain at high risk.
The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Native, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health including differences in income, education, and access to coverage and care.
They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.
More testing, treatment, and research are needed
Four experts welcomed the reaffirmation.
“It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in sexually transmitted infections in the U.S. since the 2016 published recommendations,” Judith A. O’Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, said in an interview.
“Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key,” she added.
Heidi Gullettt, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University, Cleveland, said: “The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.
“Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office,” she added.
Testing during office visits is not easy, Dr. Gullettt said, because of competing priorities, stigma associated with STIs, and testing and treatment costs.
“Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening,” Dr. Gullett pointed out. “Patients are often reluctant to do screening because of cost.”
Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center at Duke University, Durham, N.C., said that the true incidence and prevalence of syphilis is unknown.
“The more we test, the more accurate our data will be,” he said. “Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed. Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient’s health.”
Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, noted that the United States is in a syphilis epidemic.
“Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat,” he said.
In an accompanying editorial, Susan Tuddenham, MD, MPH; and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University, Baltimore, urged that funding to develop novel syphilis diagnostics be prioritized, “just as there has been for development of syphilis vaccines, which are still many years from becoming a reality.”
“Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection,” they cautioned.
The authors of the recommendation statement and the evidence report, as well as Dr. O’Donnell, Dr. Gullettt, Dr. Moody, and Dr. Hazra, who were not involved in the study, reported no relevant financial relationships. Dr. Tuddenham reported financial relationships with the pharmaceutical and publishing industries. Dr. Ghanem reported financial relationships with the publishing industry. The research was federally funded.
A version of this article first appeared on Medscape.com.
FROM JAMA
A switch to B/F/TAF keeps HIV suppressed, even with M184V/I mutation
People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.
“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .
“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.
Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.
Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.
Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.
All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.
The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
Virologic suppression well maintained
At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.
Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.
These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.
added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
Easy to administer, well tolerated, and potent
Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”
“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.
Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.
“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.
“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.
“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.
The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.
“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .
“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.
Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.
Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.
Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.
All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.
The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
Virologic suppression well maintained
At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.
Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.
These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.
added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
Easy to administer, well tolerated, and potent
Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”
“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.
Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.
“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.
“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.
“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.
The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.
“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .
“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.
Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.
Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.
Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.
All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.
The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
Virologic suppression well maintained
At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.
Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.
These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.
added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
Easy to administer, well tolerated, and potent
Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”
“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.
Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.
“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.
“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.
“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.
The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When is an allergic reaction to raw plant food due to tree pollen?
A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.
The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.
The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
PFS is common and increasingly prevalent
PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.
Symptoms from similar proteins in food
Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.
Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
Triggers depend on pollen type
PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.
Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
Diagnostic clinical history
If a patient answers yes to these questions, they almost certainly have PFS, the authors write:
- Are symptoms caused by raw fruits, nuts, carrots, or celery?
- Are the same trigger foods tolerated when they’re cooked well or roasted?
- Do symptoms come immediately or within a few minutes of eating?
- Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
- Does the patient have seasonal allergic rhinitis or sensitization to pollen?
Testing needed for some cases
Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.
Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.
An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
Dietary management
PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.
Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
Guideline helpful beyond the United Kingdom and birch pollen
Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.
“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.
“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”
Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.
“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.
“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.
“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development.
The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.
The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.
A version of this article first appeared on Medscape.com.
A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.
The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.
The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
PFS is common and increasingly prevalent
PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.
Symptoms from similar proteins in food
Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.
Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
Triggers depend on pollen type
PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.
Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
Diagnostic clinical history
If a patient answers yes to these questions, they almost certainly have PFS, the authors write:
- Are symptoms caused by raw fruits, nuts, carrots, or celery?
- Are the same trigger foods tolerated when they’re cooked well or roasted?
- Do symptoms come immediately or within a few minutes of eating?
- Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
- Does the patient have seasonal allergic rhinitis or sensitization to pollen?
Testing needed for some cases
Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.
Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.
An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
Dietary management
PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.
Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
Guideline helpful beyond the United Kingdom and birch pollen
Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.
“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.
“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”
Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.
“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.
“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.
“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development.
The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.
The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.
A version of this article first appeared on Medscape.com.
A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.
The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.
The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
PFS is common and increasingly prevalent
PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.
Symptoms from similar proteins in food
Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.
Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
Triggers depend on pollen type
PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.
Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
Diagnostic clinical history
If a patient answers yes to these questions, they almost certainly have PFS, the authors write:
- Are symptoms caused by raw fruits, nuts, carrots, or celery?
- Are the same trigger foods tolerated when they’re cooked well or roasted?
- Do symptoms come immediately or within a few minutes of eating?
- Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
- Does the patient have seasonal allergic rhinitis or sensitization to pollen?
Testing needed for some cases
Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.
Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.
An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
Dietary management
PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.
Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
Guideline helpful beyond the United Kingdom and birch pollen
Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.
“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.
“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”
Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.
“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.
“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.
“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development.
The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.
The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.
A version of this article first appeared on Medscape.com.
Lower BMI linked with better knee osteoarthritis outcomes
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
FROM ARTHRITIS & RHEUMATOLOGY
Dermatoses often occur in people who wear face masks
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
according to a recently published systematic review and meta-analysis.
“This report finds the most statistically significant risk factor for developing a facial dermatosis under a face mask is how long one wears the mask. Specifically, wearing a mask for more than 4 to 6 hours correlated most strongly with the development of a facial skin problem,” Jami L. Miller, MD, associate professor of dermatology, Vanderbilt University Medical Center, Nashville, Tenn., told this news organization. Dr. Miller was not involved in the study.
“The type of mask and the environment were of less significance,” she added.
Mask wearing for infection control has been common during the COVID-19 pandemic and will likely continue for some time, study coauthors Lim Yi Shen Justin, MBBS, and Yik Weng Yew*, MBBS, MPH, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, write in Contact Dermatitis. And cross-sectional studies have suggested a link between mask wearing and various facial dermatoses.
To evaluate this link, as well as potential risk factors for facial dermatoses, the researchers reviewed 37 studies published between 2004 and 2022 involving 29,557 adult participants self-reporting regular use of any face mask type across 17 countries in Europe and Asia. The mask types commonly studied in the papers they analyzed included surgical masks and respirators.
Facial dermatoses were self-reported in 30 studies (81.1%) and were diagnosed by trained dermatologists in seven studies (18.9%).
Dr. Justin and Dr. Yew found that:
- The overall prevalence of facial dermatoses was 55%
- Individually, facial dermatitis, itch, acne, and pressure injuries were consistently reported as facial dermatoses, with pooled prevalence rates of 24%, 30%, 31%, and 31%, respectively
- The duration of mask wearing was the most significant risk factor for facial dermatoses (P < .001)
- Respirators, including N95 masks, were not more likely than surgical masks to be linked with facial dermatoses
“Understanding risk factors of mask wearing, including situation, duration, and type of mask, may allow for targeted interventions to mitigate problems,” Dr. Yew told this news organization.
He advised taking a break from mask wearing after 4 to 6 hours to improve outcomes.
Dr. Yew acknowledged limitations, including that most of the reviewed studies relied on self-reported symptoms.
“Patient factors were not investigated in most studies; therefore, we were not able to ascertain their contributory role in the development of facial dermatoses from mask wearing,” he said. “We were also unable to prove causation between risk factors and outcome.”
Four dermatologists welcome the findings
Dr. Miller called this an “interesting, and certainly relevant” study, now that mask wearing is common and facial skin problems are fairly common complaints in medical visits.
“As the authors say, irritants or contact allergens with longer exposures can be expected to cause a more severe dermatitis than short contact,” she said. “Longer duration also can cause occlusion of pores and hair follicles, which can be expected to worsen acne and folliculitis.”
“I was surprised that the type of mask did not seem to matter significantly,” she added. “Patients wearing N95 masks may be relieved to know N95s do not cause more skin problems than lighter masks.”
Still, Dr. Miller had several questions, including if the materials and chemical finishes that vary by manufacturer may affect skin conditions.
Olga Bunimovich, MD, assistant professor, department of dermatology, University of Pittsburgh School of Medicine, Pennsylvania, called this study “an excellent step towards characterizing the role masks play in facial dermatoses.”
“The study provides a window into the prevalence of these conditions, as well as some understanding of the factors that may be contributing to it,” Dr. Bunimovich, who was not part of the study, added. But “we can also utilize this information to alter behavior in the work environment, allowing ‘mask-free’ breaks to decrease the risk of facial dermatoses.”
Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University School of Medicine, Cleveland, expected skin problems to be linked with mask wearing but didn’t expect the prevalence to be as high as 55%, which she called “very significant.”
“Mask wearing is an important means to prevent transmission of communicable infections, and the practice will most likely continue,” she said.
“Given the data, it is reasonable to advise patients who are already prone to these specific dermatoses to be proactive,” she added. “Early intervention with proper topical medications, preferably prescribed by a dermatologist or other health care provider, and changing masks frequently before they get soaked with moisture, will hopefully lessen the severity of skin rashes and minimize the negative impact on quality of life.”
Also commenting on the study, Susan Massick, MD, dermatologist and clinical associate professor of internal medicine, The Ohio State University Wexner Medical Center, Westerville, said in an interview that she urges people to wear masks, despite these risks.
“The majority of concerns are straightforward, manageable, and overall benign,” she said. “We have a multitude of treatments that can help control, address, or improve symptoms.”
“Masks are an effective and easy way to protect yourself from infection, and they remain one of the most reliable preventions we have,” Dr. Massick noted. “The findings in this article should not preclude anyone from wearing a mask, nor should facial dermatoses be a cause for people to stop wearing their masks.”
The study received no funding. The authors, as well as Dr. Baron, Dr. Miller, Dr. Bunimovich, and Dr. Massick, who were not involved in the study, reported no relevant financial relationships. All experts commented by email.
A version of this article first appeared on Medscape.com.
Correction, 9/22/22: An earlier version of this article misstated the name of Dr. Yik Weng Yew.
Hydroquinone, found in skin-lightening agents worldwide, linked with increased skin cancer risk
an analysis of records from a large research database suggests.
In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”
The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.
Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.
The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).
Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.
The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.
They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)
While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
Skin lightening is big business and more research is needed
“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.
Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.
“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.
Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.
The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.
“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?
“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”
These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.
“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.
Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.
“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.
“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.
“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.
The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.
A version of this article first appeared on Medscape.com.
an analysis of records from a large research database suggests.
In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”
The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.
Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.
The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).
Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.
The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.
They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)
While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
Skin lightening is big business and more research is needed
“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.
Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.
“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.
Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.
The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.
“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?
“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”
These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.
“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.
Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.
“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.
“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.
“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.
The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.
A version of this article first appeared on Medscape.com.
an analysis of records from a large research database suggests.
In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”
The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.
Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.
The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).
Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.
The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.
They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)
While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
Skin lightening is big business and more research is needed
“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.
Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.
“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.
Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.
The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.
“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?
“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”
These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.
“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.
Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.
“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.
“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.
“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.
The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.
A version of this article first appeared on Medscape.com.
FROM SID 2022
Ultrasound helps predict gout flares over the next year
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM RHEUMATOLOGY