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Mechanistic link between herpes virus, Alzheimer’s revealed?
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
IV nutrition becoming the norm for athletes despite no evidence it works
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE
Dermatology and monkeypox: What you need to know
.
Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.
To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.
To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.
But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.
Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”
Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
Know your lesions
Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).
However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”
Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.
Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”
Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.
Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)
It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).
Testing is crucial to rule monkeypox in – or out
While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”
Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.
As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”
It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”
In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”
Recommendations pending on scarring prevention
There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”
He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.
“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”
Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”
As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”
The dermatologists interviewed for this article report no disclosures.
.
Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.
To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.
To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.
But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.
Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”
Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
Know your lesions
Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).
However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”
Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.
Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”
Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.
Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)
It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).
Testing is crucial to rule monkeypox in – or out
While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”
Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.
As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”
It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”
In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”
Recommendations pending on scarring prevention
There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”
He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.
“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”
Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”
As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”
The dermatologists interviewed for this article report no disclosures.
.
Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.
To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.
To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.
But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.
Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”
Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
Know your lesions
Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).
However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”
Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.
Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”
Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.
Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)
It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).
Testing is crucial to rule monkeypox in – or out
While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”
Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.
As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”
It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”
In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”
Recommendations pending on scarring prevention
There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”
He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.
“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”
Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”
As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”
The dermatologists interviewed for this article report no disclosures.
Strength training overcomes bone effects of vegan diet
People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.
“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.
“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”
The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Exercise significantly impacts bone health in vegans
The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.
However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.
“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.
“By ignoring these effects, important factors influencing bone health are neglected.”
For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.
Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.
Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m2), being age 30-50 years, and being premenopausal.
Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.
Vegan bone deficits disappear with strength training
Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).
Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.
However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.
Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.
Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.
Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.
“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”
Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.
“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
Mechanisms
The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.
The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.
“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.
“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.
Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.
“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.
“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”
The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Exercise significantly impacts bone health in vegans
The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.
However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.
“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.
“By ignoring these effects, important factors influencing bone health are neglected.”
For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.
Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.
Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m2), being age 30-50 years, and being premenopausal.
Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.
Vegan bone deficits disappear with strength training
Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).
Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.
However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.
Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.
Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.
Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.
“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”
Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.
“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
Mechanisms
The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.
The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.
“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.
“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.
Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.
“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.
“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”
The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Exercise significantly impacts bone health in vegans
The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.
However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.
“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.
“By ignoring these effects, important factors influencing bone health are neglected.”
For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.
Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.
Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m2), being age 30-50 years, and being premenopausal.
Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.
Vegan bone deficits disappear with strength training
Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).
Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.
However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.
Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.
Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.
Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.
“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”
Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.
“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
Mechanisms
The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.
The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.
“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.
“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.
Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Review cautions against influencer-promoted hair-growth remedies
One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.
Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.
From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .
They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”
Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.
“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.
For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..
Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”
The study was independently supported. Dr. Farah reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.
Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.
From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .
They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”
Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.
“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.
For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..
Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”
The study was independently supported. Dr. Farah reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.
Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.
From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .
They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”
Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.
“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.
For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..
Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”
The study was independently supported. Dr. Farah reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF COSMETIC DERMATOLOGY
Getting cancer research on track again may require a ‘behemoth’ effort
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
Which factors fuel sexual violence in health care?
At the beginning of July, Brazilians across the country were appalled when they heard that an anesthesiologist was accused of sexually abusing a woman he had been treating during cesarean delivery. The incident was recorded on video by nurses and nurse technicians who, having become suspicious of the excessive amount of sedatives given to mothers-to-be by this particular anesthesiologist, decided to film him during a procedure. To do this, they made a last-minute change, switching delivery rooms to one in which they had hidden a cell phone in a cabinet.
What the footage showed was horrifying and the assailant, Giovanni Quintella Bezerra, was arrested on the spot. He’s a 32-year-old, White, successful physician, and he’s now accused of rape. The authorities are looking into whether there are more victims, others who may have been abused by the physician. The police are investigating about 40 surgeries in which Dr. Bezerra participated. That same month saw the arrest of another physician, gynecologist Ricardo Teles Martins, who was arrested after being accused of sexually harassing and abusing several women in Hidrolândia, in the northeastern state of Ceará.
In gathering information about these incidents, this news organization interviewed four Brazilian specialists to get their insights on the issues that have been brought to light by these recent cases and the factors that play a role in these kinds of criminal acts. Claudio Cohen, MD, PhD, is a psychiatrist, bioethicist, and professor at the University of São Paulo in Brazil. Daniela Pedroso, MA, is a psychologist who has 25 years’ experience working with victims of sexual violence. Gynecologist and obstetrician Jefferson Drezett, MD, PhD, is a professor in the field of population genetics and reproductive and sexual health at the Federal University of ABC, São Paulo, and in the department of health, life cycles, and society at the University of São Paulo School of Public Health. Maria Alice Scardoelli, MD, is a psychiatrist who also serves as vice-chair of the São Paulo Regional Council of Medicine (Cremesp).
Accusations and investigations
Not all incidents of sexual violence in health care institutions are reported, and precise numbers are difficult to obtain. The fact that there are any cases at all is troubling. In 2019, journalists from The Intercept found that over a period of 6 years (2014-2019), 1,734 such attacks were recorded in nine Brazilian states. They were able to get that information from the states’ Public Security Secretariats by using the Information Access Act, a law that regulates the right to access public information.
Efforts to determine how widespread this type of sexual violence is are further complicated by the difficulties in collating the accusations filed at each state’s regional council of medicine, police stations, and public prosecutor’s office. Which investigative steps are taken depends upon where the report was filed, and only occasionally do these entities communicate with each other. According to its data, Cremesp received 78 accusations in 2019. In 2020, that number increased to 84. In 2021, it was 83; these types of attacks were the seventh most common among the investigations opened that year. In the first 6 months of 2022, there were 36 complaints. The number includes investigations opened on the basis of press reports. In such cases, enough information must be available in the press reports make it possible to initiate an evaluation and assessment of the matter. There is no information about how many accusations became the subject of professional ethics proceedings and how many were formally adjudicated.
“Each accusation received is investigated by a technical committee made up of professionals from various specialties. There really needs to be a rigorous evaluation and assessment during the investigation. We cannot be unfair: It may turn out that there was no truth to the accusation after all, and yet someone’s career may already have been destroyed,” explained Dr. Scardoelli.
After the accusation is investigated and accepted by Cremesp, there is no deadline by which the proceedings must end. They can take up to 5 years, and sometimes longer. Since March, however, a deadline for the investigation period has been in effect, after which the proceedings can commence.
“We now have 90 days to make an evaluation and assessment in the investigation phase; that time period can be extended by 3 months, starting from the date the accusation is submitted to the council. If the case is accepted, then the proceedings are opened,” Dr. Scardoelli said.
Some incidents are not reported by victims. And there are incidents that are reported only after many years have passed. This was the case with Nina Marqueti, the actress at the center of #OndeDói — “Where It Hurts” — a campaign that was launched to raise awareness about sexual violence committed by health care professionals. When she was 16, her pediatrician sexually abused her. It wasn’t until 2019, more than a decade later, that she felt able to make this accusation known publicly.
Almost immediately, the campaign received over 4,000 posts online. Most of them were people’s accounts of acts of violence committed by physicians during appointments in their offices or during treatment in a hospital. These are available on Twitter under the hashtag #ondedoi.
Inadequate sex education?
News reports about physicians who abuse patients have a tremendous impact on the public. People are genuinely surprised when they hear the words “health care professional” and “sex attack” in the same sentence. “One of the most disturbing aspects is that health care professionals are committing these acts of violence against women who are in a vulnerable state, typically when they’re under anesthesia, they’ve fallen ill, or when the health care professional introduces an element of deception into the procedure so as to create the opportunity to abuse the patient in some way,” said Dr. Drezett.
As Dr. Cohen sees it, to perpetrate these acts of sexual violence, physicians – as well as lawyers, religious leaders, judges, politicians, police officers, and other persons in a position of trust – make use of their power to take advantage of a person’s vulnerability. “Physicians, lawyers, police officers, religious leaders, dads, bosses, husbands – the people who commit sexual abuse all have something in common,” he said. “In terms of the emotional aspect, all of them are taking advantage of both the power that their position holds in society and the asymmetrical power dynamics that exist between them and the other person.”
Indeed, anyone who knocks on a physician’s door seeking a diagnosis or treatment, anyone who knocks on a lawyer’s door seeking assistance, is putting themselves in a fragile situation. “The abuser considers the other person an object, not a human being who has rights,” said Dr. Cohen. People who fit the psychological and behavioral profile of a sexual assailant find in these “powerful” professions and in the circumstances and opportunities these professions provide a means to fulfill their desires. In medicine, however, there is yet another imbalance, one involving consent to touch a person’s body.
The age of the recently arrested anesthesiologist is something that caught Dr. Cohen’s attention. As noted in one of his many books, Bioética e Sexualidade nas Relações Profissionais [Bioethics and Sexuality in Professional Relationships], published in 1999 by the São Paulo Medical Association, age is a characteristic that repeatedly came up in his analysis of 150 sexual abuse proceedings handled by Cremesp.
“When I looked over the cases, I saw that most of the abusers were not right out of med school in their twenties – a time when sex is at the forefront of one’s life – nor were the abusers on the older end of the age spectrum. The abusers were, in fact, those who had already had several years of experience – as was the case with this 32-year-old anesthesiologist who, at a particular moment in time, breached all prohibitions and betrayed the expectations that society had of him as a physician: to care for people’s well-being and to alleviate their suffering. There was nothing that could hold him back from fulfilling his desire, not even the presence of nurses and other physicians in the operating room.” As for the findings of Dr. Cohen’s review, the majority of the 150 cases were dismissed because of lack of evidence.
To Ms. Pedroso, who has treated more than 12,000 victims of sexual harassment, it’s the questioning and intimidation that women feel in relationship to the male physician – a person who is viewed as holding knowledge about her body – that leaves them vulnerable and more subject to acts of violence, especially in more remote places. “We’re speaking, yet again, about rape culture. Not many people know what that term means, but, generally speaking, it has to do with the objectification of women’s bodies and the issue of boys growing up thinking they have the right to touch girls and women and that they will go unpunished for doing so.”
The lack of sex education and efforts to prevent sexual abuse are contributing factors for why the situation remains unchanged. “We are long overdue. We live in a country where there’s this completely mistaken belief that talking about sex education involves teaching children how to have sex, as opposed to teaching them how to protect themselves. We teach girls that they have to protect themselves from being raped, but we don’t teach boys not to rape.”
Another point highlighted by Ms. Pedroso is the fact that to carry out their actions, sexual assailants seek out-of-the-way places, places where they believe the rules can be bent and where they won’t be caught. This is what may have happened with Dr. Bezerra. During a recent press conference, the coordinator of the Health Section of the Rio de Janeiro Public Defender’s Office, Thaísa Guerreiro, stated that although the Women’s Hospital in São João do Meriti – one of the places where the assailant worked as an anesthesiologist – had adopted protocols to protect patients, it failed to enforce them. Another observation was that the health care professionals normalized violations of a woman’s right to have a companion present throughout labor and delivery, a right guaranteed by federal law. Ms. Guerreiro went on to say that the hospital’s chief of anesthesia and the state’s health coordination office did not question this, nor did they find it strange or surprising. According to witness statements, Dr. Bezerra would ask the patients’ husbands to leave the room in the middle of the procedure.
It should be clarified, Dr. Drezett mentioned, that although obstetric violence and sexual abuse overlap in places, they do not have the same root cause or definition. “There are two sets of situations that we term ‘obstetric violence.’ One involves any type of disrespectful treatment, whether comments or neglect, during pregnancy, delivery, or the postpartum period. The other refers to health care professionals’ attitudes in imposing inadequate and outdated medical procedures at the time of birth, such as keeping the woman fasting, having her pubic hair removed, and inducing labor or speeding up the delivery with oxytocin and [routine] episiotomy, among other things.”
Early education crucial
How are health care institutions dealing with this problem? “Very poorly. Sexual violence perpetrated by physicians and other health care professionals is a taboo subject that people are still afraid to talk about,” Dr. Cohen observed. “Regrettably, sexual violence happens all too often. Before, maybe we weren’t talking about it much because, from our viewpoint, health care professionals, such as physicians and nurses, weren’t likely to commit acts of violence while performing their duties,” noted Dr. Drezett.
Dr. Drezett also spoke about schools and what role they can play. “Of course, schools should discuss violence against women, especially in the field of health care. This has been done for a long time now, though it’s not in every curriculum in every medical school or nursing school, nor in every school of social work or of psychology,” said Dr. Drezett. For example, in the bioethics classes taken in the third and fourth years of the University of São Paolo’s medical degree program, Dr. Cohen asks students to reflect on the significance of being in a position where you ask a patient you’ve never met to undress so you can perform an exam, and the patient promptly and readily complies. “This is not about the physician, it’s about the power of the institution,” the professor pointed out. Sexual violence is a problem on the university campus as well. Another front in the battle has formed across various schools, where groups of students have created feminist collectives to have sexual violence and other issues related to gender-based violence added to the agenda.
Dr. Drezett said it’s very unlikely that efforts made during a degree program are going to succeed in preventing students who are prone to commit sexual violence from engaging in such behavior. “We’re talking about gender-specific lessons, where discussions about gender-based violence should be started much, much earlier – parents talking to their children, teachers talking to their pupils.” He also doesn’t believe that the molesters are dissuaded by the fact that these accusations get publicized in the media. “If they were, the Roger Abdelmassih case would have done away with the problem.”
On the other hand, Dr. Drezett suggested, publicizing these stories can help to bring very positive issues out into the open. What the Bezerra case made clear was that laws were not followed and rights were not protected. An environment was thus created in which the sexual crime could be perpetrated, with nurses coming to suspect acts of obstetric violence, such as use of sedation, which prevented the woman from having skin-to-skin contact with the newborn and from breastfeeding within the first few hours of birth – two clinical practices that are recommended the world over.
“Health care professionals who act properly, in accordance with best practices for interacting with others and performing daily duties, at all times, in public or private practice – they remove themselves from situations like those described in the Bezerra case; they don’t practice medicine in a reckless manner,” said Dr. Drezett.
Another negative aspect of all this, he said, is that the suspicion and wariness that patients feel may spread far and wide. “Among my colleagues are anesthetists and anesthesiologists with impeccable ethical and professional records. They are very upset that people are now regarding them with doubt and uncertainty. We need to make it clear that those horrifying cases are the exceptions, not the rule,” he said. There is also a need to correct the misconception that such abuse is always in some way associated with obstetrics and gynecology.
“This is not true. These incidents can happen in any doctor’s office. It all depends on the physician – whether he or she has designs on committing a criminal act,” Dr. Drezett noted. He did point out that there are few sexual molesters among health care professionals, though there are numerous cases. Yet this in no way diminishes the seriousness of the incidents. “Of course, we’re speaking again about the exceptions, but in my experience of treating victims, I’ve seen, for example, more cases where it’s been a police officer, not a physician, committing an act of sexual violence against a woman,” he stated.
The nurses and nurse technicians at São João do Meriti Hospital who reported the abuser acted very assertively. If they hadn’t gathered the evidence to back up their accusations, it’s possible that the physician wouldn’t have been caught in the act and that the case would have taken a different course – including pressure being put on them and their becoming the target of retaliation.
A version of this article first appeared on Medscape.com. This article was translated from the Medscape Portuguese edition.
At the beginning of July, Brazilians across the country were appalled when they heard that an anesthesiologist was accused of sexually abusing a woman he had been treating during cesarean delivery. The incident was recorded on video by nurses and nurse technicians who, having become suspicious of the excessive amount of sedatives given to mothers-to-be by this particular anesthesiologist, decided to film him during a procedure. To do this, they made a last-minute change, switching delivery rooms to one in which they had hidden a cell phone in a cabinet.
What the footage showed was horrifying and the assailant, Giovanni Quintella Bezerra, was arrested on the spot. He’s a 32-year-old, White, successful physician, and he’s now accused of rape. The authorities are looking into whether there are more victims, others who may have been abused by the physician. The police are investigating about 40 surgeries in which Dr. Bezerra participated. That same month saw the arrest of another physician, gynecologist Ricardo Teles Martins, who was arrested after being accused of sexually harassing and abusing several women in Hidrolândia, in the northeastern state of Ceará.
In gathering information about these incidents, this news organization interviewed four Brazilian specialists to get their insights on the issues that have been brought to light by these recent cases and the factors that play a role in these kinds of criminal acts. Claudio Cohen, MD, PhD, is a psychiatrist, bioethicist, and professor at the University of São Paulo in Brazil. Daniela Pedroso, MA, is a psychologist who has 25 years’ experience working with victims of sexual violence. Gynecologist and obstetrician Jefferson Drezett, MD, PhD, is a professor in the field of population genetics and reproductive and sexual health at the Federal University of ABC, São Paulo, and in the department of health, life cycles, and society at the University of São Paulo School of Public Health. Maria Alice Scardoelli, MD, is a psychiatrist who also serves as vice-chair of the São Paulo Regional Council of Medicine (Cremesp).
Accusations and investigations
Not all incidents of sexual violence in health care institutions are reported, and precise numbers are difficult to obtain. The fact that there are any cases at all is troubling. In 2019, journalists from The Intercept found that over a period of 6 years (2014-2019), 1,734 such attacks were recorded in nine Brazilian states. They were able to get that information from the states’ Public Security Secretariats by using the Information Access Act, a law that regulates the right to access public information.
Efforts to determine how widespread this type of sexual violence is are further complicated by the difficulties in collating the accusations filed at each state’s regional council of medicine, police stations, and public prosecutor’s office. Which investigative steps are taken depends upon where the report was filed, and only occasionally do these entities communicate with each other. According to its data, Cremesp received 78 accusations in 2019. In 2020, that number increased to 84. In 2021, it was 83; these types of attacks were the seventh most common among the investigations opened that year. In the first 6 months of 2022, there were 36 complaints. The number includes investigations opened on the basis of press reports. In such cases, enough information must be available in the press reports make it possible to initiate an evaluation and assessment of the matter. There is no information about how many accusations became the subject of professional ethics proceedings and how many were formally adjudicated.
“Each accusation received is investigated by a technical committee made up of professionals from various specialties. There really needs to be a rigorous evaluation and assessment during the investigation. We cannot be unfair: It may turn out that there was no truth to the accusation after all, and yet someone’s career may already have been destroyed,” explained Dr. Scardoelli.
After the accusation is investigated and accepted by Cremesp, there is no deadline by which the proceedings must end. They can take up to 5 years, and sometimes longer. Since March, however, a deadline for the investigation period has been in effect, after which the proceedings can commence.
“We now have 90 days to make an evaluation and assessment in the investigation phase; that time period can be extended by 3 months, starting from the date the accusation is submitted to the council. If the case is accepted, then the proceedings are opened,” Dr. Scardoelli said.
Some incidents are not reported by victims. And there are incidents that are reported only after many years have passed. This was the case with Nina Marqueti, the actress at the center of #OndeDói — “Where It Hurts” — a campaign that was launched to raise awareness about sexual violence committed by health care professionals. When she was 16, her pediatrician sexually abused her. It wasn’t until 2019, more than a decade later, that she felt able to make this accusation known publicly.
Almost immediately, the campaign received over 4,000 posts online. Most of them were people’s accounts of acts of violence committed by physicians during appointments in their offices or during treatment in a hospital. These are available on Twitter under the hashtag #ondedoi.
Inadequate sex education?
News reports about physicians who abuse patients have a tremendous impact on the public. People are genuinely surprised when they hear the words “health care professional” and “sex attack” in the same sentence. “One of the most disturbing aspects is that health care professionals are committing these acts of violence against women who are in a vulnerable state, typically when they’re under anesthesia, they’ve fallen ill, or when the health care professional introduces an element of deception into the procedure so as to create the opportunity to abuse the patient in some way,” said Dr. Drezett.
As Dr. Cohen sees it, to perpetrate these acts of sexual violence, physicians – as well as lawyers, religious leaders, judges, politicians, police officers, and other persons in a position of trust – make use of their power to take advantage of a person’s vulnerability. “Physicians, lawyers, police officers, religious leaders, dads, bosses, husbands – the people who commit sexual abuse all have something in common,” he said. “In terms of the emotional aspect, all of them are taking advantage of both the power that their position holds in society and the asymmetrical power dynamics that exist between them and the other person.”
Indeed, anyone who knocks on a physician’s door seeking a diagnosis or treatment, anyone who knocks on a lawyer’s door seeking assistance, is putting themselves in a fragile situation. “The abuser considers the other person an object, not a human being who has rights,” said Dr. Cohen. People who fit the psychological and behavioral profile of a sexual assailant find in these “powerful” professions and in the circumstances and opportunities these professions provide a means to fulfill their desires. In medicine, however, there is yet another imbalance, one involving consent to touch a person’s body.
The age of the recently arrested anesthesiologist is something that caught Dr. Cohen’s attention. As noted in one of his many books, Bioética e Sexualidade nas Relações Profissionais [Bioethics and Sexuality in Professional Relationships], published in 1999 by the São Paulo Medical Association, age is a characteristic that repeatedly came up in his analysis of 150 sexual abuse proceedings handled by Cremesp.
“When I looked over the cases, I saw that most of the abusers were not right out of med school in their twenties – a time when sex is at the forefront of one’s life – nor were the abusers on the older end of the age spectrum. The abusers were, in fact, those who had already had several years of experience – as was the case with this 32-year-old anesthesiologist who, at a particular moment in time, breached all prohibitions and betrayed the expectations that society had of him as a physician: to care for people’s well-being and to alleviate their suffering. There was nothing that could hold him back from fulfilling his desire, not even the presence of nurses and other physicians in the operating room.” As for the findings of Dr. Cohen’s review, the majority of the 150 cases were dismissed because of lack of evidence.
To Ms. Pedroso, who has treated more than 12,000 victims of sexual harassment, it’s the questioning and intimidation that women feel in relationship to the male physician – a person who is viewed as holding knowledge about her body – that leaves them vulnerable and more subject to acts of violence, especially in more remote places. “We’re speaking, yet again, about rape culture. Not many people know what that term means, but, generally speaking, it has to do with the objectification of women’s bodies and the issue of boys growing up thinking they have the right to touch girls and women and that they will go unpunished for doing so.”
The lack of sex education and efforts to prevent sexual abuse are contributing factors for why the situation remains unchanged. “We are long overdue. We live in a country where there’s this completely mistaken belief that talking about sex education involves teaching children how to have sex, as opposed to teaching them how to protect themselves. We teach girls that they have to protect themselves from being raped, but we don’t teach boys not to rape.”
Another point highlighted by Ms. Pedroso is the fact that to carry out their actions, sexual assailants seek out-of-the-way places, places where they believe the rules can be bent and where they won’t be caught. This is what may have happened with Dr. Bezerra. During a recent press conference, the coordinator of the Health Section of the Rio de Janeiro Public Defender’s Office, Thaísa Guerreiro, stated that although the Women’s Hospital in São João do Meriti – one of the places where the assailant worked as an anesthesiologist – had adopted protocols to protect patients, it failed to enforce them. Another observation was that the health care professionals normalized violations of a woman’s right to have a companion present throughout labor and delivery, a right guaranteed by federal law. Ms. Guerreiro went on to say that the hospital’s chief of anesthesia and the state’s health coordination office did not question this, nor did they find it strange or surprising. According to witness statements, Dr. Bezerra would ask the patients’ husbands to leave the room in the middle of the procedure.
It should be clarified, Dr. Drezett mentioned, that although obstetric violence and sexual abuse overlap in places, they do not have the same root cause or definition. “There are two sets of situations that we term ‘obstetric violence.’ One involves any type of disrespectful treatment, whether comments or neglect, during pregnancy, delivery, or the postpartum period. The other refers to health care professionals’ attitudes in imposing inadequate and outdated medical procedures at the time of birth, such as keeping the woman fasting, having her pubic hair removed, and inducing labor or speeding up the delivery with oxytocin and [routine] episiotomy, among other things.”
Early education crucial
How are health care institutions dealing with this problem? “Very poorly. Sexual violence perpetrated by physicians and other health care professionals is a taboo subject that people are still afraid to talk about,” Dr. Cohen observed. “Regrettably, sexual violence happens all too often. Before, maybe we weren’t talking about it much because, from our viewpoint, health care professionals, such as physicians and nurses, weren’t likely to commit acts of violence while performing their duties,” noted Dr. Drezett.
Dr. Drezett also spoke about schools and what role they can play. “Of course, schools should discuss violence against women, especially in the field of health care. This has been done for a long time now, though it’s not in every curriculum in every medical school or nursing school, nor in every school of social work or of psychology,” said Dr. Drezett. For example, in the bioethics classes taken in the third and fourth years of the University of São Paolo’s medical degree program, Dr. Cohen asks students to reflect on the significance of being in a position where you ask a patient you’ve never met to undress so you can perform an exam, and the patient promptly and readily complies. “This is not about the physician, it’s about the power of the institution,” the professor pointed out. Sexual violence is a problem on the university campus as well. Another front in the battle has formed across various schools, where groups of students have created feminist collectives to have sexual violence and other issues related to gender-based violence added to the agenda.
Dr. Drezett said it’s very unlikely that efforts made during a degree program are going to succeed in preventing students who are prone to commit sexual violence from engaging in such behavior. “We’re talking about gender-specific lessons, where discussions about gender-based violence should be started much, much earlier – parents talking to their children, teachers talking to their pupils.” He also doesn’t believe that the molesters are dissuaded by the fact that these accusations get publicized in the media. “If they were, the Roger Abdelmassih case would have done away with the problem.”
On the other hand, Dr. Drezett suggested, publicizing these stories can help to bring very positive issues out into the open. What the Bezerra case made clear was that laws were not followed and rights were not protected. An environment was thus created in which the sexual crime could be perpetrated, with nurses coming to suspect acts of obstetric violence, such as use of sedation, which prevented the woman from having skin-to-skin contact with the newborn and from breastfeeding within the first few hours of birth – two clinical practices that are recommended the world over.
“Health care professionals who act properly, in accordance with best practices for interacting with others and performing daily duties, at all times, in public or private practice – they remove themselves from situations like those described in the Bezerra case; they don’t practice medicine in a reckless manner,” said Dr. Drezett.
Another negative aspect of all this, he said, is that the suspicion and wariness that patients feel may spread far and wide. “Among my colleagues are anesthetists and anesthesiologists with impeccable ethical and professional records. They are very upset that people are now regarding them with doubt and uncertainty. We need to make it clear that those horrifying cases are the exceptions, not the rule,” he said. There is also a need to correct the misconception that such abuse is always in some way associated with obstetrics and gynecology.
“This is not true. These incidents can happen in any doctor’s office. It all depends on the physician – whether he or she has designs on committing a criminal act,” Dr. Drezett noted. He did point out that there are few sexual molesters among health care professionals, though there are numerous cases. Yet this in no way diminishes the seriousness of the incidents. “Of course, we’re speaking again about the exceptions, but in my experience of treating victims, I’ve seen, for example, more cases where it’s been a police officer, not a physician, committing an act of sexual violence against a woman,” he stated.
The nurses and nurse technicians at São João do Meriti Hospital who reported the abuser acted very assertively. If they hadn’t gathered the evidence to back up their accusations, it’s possible that the physician wouldn’t have been caught in the act and that the case would have taken a different course – including pressure being put on them and their becoming the target of retaliation.
A version of this article first appeared on Medscape.com. This article was translated from the Medscape Portuguese edition.
At the beginning of July, Brazilians across the country were appalled when they heard that an anesthesiologist was accused of sexually abusing a woman he had been treating during cesarean delivery. The incident was recorded on video by nurses and nurse technicians who, having become suspicious of the excessive amount of sedatives given to mothers-to-be by this particular anesthesiologist, decided to film him during a procedure. To do this, they made a last-minute change, switching delivery rooms to one in which they had hidden a cell phone in a cabinet.
What the footage showed was horrifying and the assailant, Giovanni Quintella Bezerra, was arrested on the spot. He’s a 32-year-old, White, successful physician, and he’s now accused of rape. The authorities are looking into whether there are more victims, others who may have been abused by the physician. The police are investigating about 40 surgeries in which Dr. Bezerra participated. That same month saw the arrest of another physician, gynecologist Ricardo Teles Martins, who was arrested after being accused of sexually harassing and abusing several women in Hidrolândia, in the northeastern state of Ceará.
In gathering information about these incidents, this news organization interviewed four Brazilian specialists to get their insights on the issues that have been brought to light by these recent cases and the factors that play a role in these kinds of criminal acts. Claudio Cohen, MD, PhD, is a psychiatrist, bioethicist, and professor at the University of São Paulo in Brazil. Daniela Pedroso, MA, is a psychologist who has 25 years’ experience working with victims of sexual violence. Gynecologist and obstetrician Jefferson Drezett, MD, PhD, is a professor in the field of population genetics and reproductive and sexual health at the Federal University of ABC, São Paulo, and in the department of health, life cycles, and society at the University of São Paulo School of Public Health. Maria Alice Scardoelli, MD, is a psychiatrist who also serves as vice-chair of the São Paulo Regional Council of Medicine (Cremesp).
Accusations and investigations
Not all incidents of sexual violence in health care institutions are reported, and precise numbers are difficult to obtain. The fact that there are any cases at all is troubling. In 2019, journalists from The Intercept found that over a period of 6 years (2014-2019), 1,734 such attacks were recorded in nine Brazilian states. They were able to get that information from the states’ Public Security Secretariats by using the Information Access Act, a law that regulates the right to access public information.
Efforts to determine how widespread this type of sexual violence is are further complicated by the difficulties in collating the accusations filed at each state’s regional council of medicine, police stations, and public prosecutor’s office. Which investigative steps are taken depends upon where the report was filed, and only occasionally do these entities communicate with each other. According to its data, Cremesp received 78 accusations in 2019. In 2020, that number increased to 84. In 2021, it was 83; these types of attacks were the seventh most common among the investigations opened that year. In the first 6 months of 2022, there were 36 complaints. The number includes investigations opened on the basis of press reports. In such cases, enough information must be available in the press reports make it possible to initiate an evaluation and assessment of the matter. There is no information about how many accusations became the subject of professional ethics proceedings and how many were formally adjudicated.
“Each accusation received is investigated by a technical committee made up of professionals from various specialties. There really needs to be a rigorous evaluation and assessment during the investigation. We cannot be unfair: It may turn out that there was no truth to the accusation after all, and yet someone’s career may already have been destroyed,” explained Dr. Scardoelli.
After the accusation is investigated and accepted by Cremesp, there is no deadline by which the proceedings must end. They can take up to 5 years, and sometimes longer. Since March, however, a deadline for the investigation period has been in effect, after which the proceedings can commence.
“We now have 90 days to make an evaluation and assessment in the investigation phase; that time period can be extended by 3 months, starting from the date the accusation is submitted to the council. If the case is accepted, then the proceedings are opened,” Dr. Scardoelli said.
Some incidents are not reported by victims. And there are incidents that are reported only after many years have passed. This was the case with Nina Marqueti, the actress at the center of #OndeDói — “Where It Hurts” — a campaign that was launched to raise awareness about sexual violence committed by health care professionals. When she was 16, her pediatrician sexually abused her. It wasn’t until 2019, more than a decade later, that she felt able to make this accusation known publicly.
Almost immediately, the campaign received over 4,000 posts online. Most of them were people’s accounts of acts of violence committed by physicians during appointments in their offices or during treatment in a hospital. These are available on Twitter under the hashtag #ondedoi.
Inadequate sex education?
News reports about physicians who abuse patients have a tremendous impact on the public. People are genuinely surprised when they hear the words “health care professional” and “sex attack” in the same sentence. “One of the most disturbing aspects is that health care professionals are committing these acts of violence against women who are in a vulnerable state, typically when they’re under anesthesia, they’ve fallen ill, or when the health care professional introduces an element of deception into the procedure so as to create the opportunity to abuse the patient in some way,” said Dr. Drezett.
As Dr. Cohen sees it, to perpetrate these acts of sexual violence, physicians – as well as lawyers, religious leaders, judges, politicians, police officers, and other persons in a position of trust – make use of their power to take advantage of a person’s vulnerability. “Physicians, lawyers, police officers, religious leaders, dads, bosses, husbands – the people who commit sexual abuse all have something in common,” he said. “In terms of the emotional aspect, all of them are taking advantage of both the power that their position holds in society and the asymmetrical power dynamics that exist between them and the other person.”
Indeed, anyone who knocks on a physician’s door seeking a diagnosis or treatment, anyone who knocks on a lawyer’s door seeking assistance, is putting themselves in a fragile situation. “The abuser considers the other person an object, not a human being who has rights,” said Dr. Cohen. People who fit the psychological and behavioral profile of a sexual assailant find in these “powerful” professions and in the circumstances and opportunities these professions provide a means to fulfill their desires. In medicine, however, there is yet another imbalance, one involving consent to touch a person’s body.
The age of the recently arrested anesthesiologist is something that caught Dr. Cohen’s attention. As noted in one of his many books, Bioética e Sexualidade nas Relações Profissionais [Bioethics and Sexuality in Professional Relationships], published in 1999 by the São Paulo Medical Association, age is a characteristic that repeatedly came up in his analysis of 150 sexual abuse proceedings handled by Cremesp.
“When I looked over the cases, I saw that most of the abusers were not right out of med school in their twenties – a time when sex is at the forefront of one’s life – nor were the abusers on the older end of the age spectrum. The abusers were, in fact, those who had already had several years of experience – as was the case with this 32-year-old anesthesiologist who, at a particular moment in time, breached all prohibitions and betrayed the expectations that society had of him as a physician: to care for people’s well-being and to alleviate their suffering. There was nothing that could hold him back from fulfilling his desire, not even the presence of nurses and other physicians in the operating room.” As for the findings of Dr. Cohen’s review, the majority of the 150 cases were dismissed because of lack of evidence.
To Ms. Pedroso, who has treated more than 12,000 victims of sexual harassment, it’s the questioning and intimidation that women feel in relationship to the male physician – a person who is viewed as holding knowledge about her body – that leaves them vulnerable and more subject to acts of violence, especially in more remote places. “We’re speaking, yet again, about rape culture. Not many people know what that term means, but, generally speaking, it has to do with the objectification of women’s bodies and the issue of boys growing up thinking they have the right to touch girls and women and that they will go unpunished for doing so.”
The lack of sex education and efforts to prevent sexual abuse are contributing factors for why the situation remains unchanged. “We are long overdue. We live in a country where there’s this completely mistaken belief that talking about sex education involves teaching children how to have sex, as opposed to teaching them how to protect themselves. We teach girls that they have to protect themselves from being raped, but we don’t teach boys not to rape.”
Another point highlighted by Ms. Pedroso is the fact that to carry out their actions, sexual assailants seek out-of-the-way places, places where they believe the rules can be bent and where they won’t be caught. This is what may have happened with Dr. Bezerra. During a recent press conference, the coordinator of the Health Section of the Rio de Janeiro Public Defender’s Office, Thaísa Guerreiro, stated that although the Women’s Hospital in São João do Meriti – one of the places where the assailant worked as an anesthesiologist – had adopted protocols to protect patients, it failed to enforce them. Another observation was that the health care professionals normalized violations of a woman’s right to have a companion present throughout labor and delivery, a right guaranteed by federal law. Ms. Guerreiro went on to say that the hospital’s chief of anesthesia and the state’s health coordination office did not question this, nor did they find it strange or surprising. According to witness statements, Dr. Bezerra would ask the patients’ husbands to leave the room in the middle of the procedure.
It should be clarified, Dr. Drezett mentioned, that although obstetric violence and sexual abuse overlap in places, they do not have the same root cause or definition. “There are two sets of situations that we term ‘obstetric violence.’ One involves any type of disrespectful treatment, whether comments or neglect, during pregnancy, delivery, or the postpartum period. The other refers to health care professionals’ attitudes in imposing inadequate and outdated medical procedures at the time of birth, such as keeping the woman fasting, having her pubic hair removed, and inducing labor or speeding up the delivery with oxytocin and [routine] episiotomy, among other things.”
Early education crucial
How are health care institutions dealing with this problem? “Very poorly. Sexual violence perpetrated by physicians and other health care professionals is a taboo subject that people are still afraid to talk about,” Dr. Cohen observed. “Regrettably, sexual violence happens all too often. Before, maybe we weren’t talking about it much because, from our viewpoint, health care professionals, such as physicians and nurses, weren’t likely to commit acts of violence while performing their duties,” noted Dr. Drezett.
Dr. Drezett also spoke about schools and what role they can play. “Of course, schools should discuss violence against women, especially in the field of health care. This has been done for a long time now, though it’s not in every curriculum in every medical school or nursing school, nor in every school of social work or of psychology,” said Dr. Drezett. For example, in the bioethics classes taken in the third and fourth years of the University of São Paolo’s medical degree program, Dr. Cohen asks students to reflect on the significance of being in a position where you ask a patient you’ve never met to undress so you can perform an exam, and the patient promptly and readily complies. “This is not about the physician, it’s about the power of the institution,” the professor pointed out. Sexual violence is a problem on the university campus as well. Another front in the battle has formed across various schools, where groups of students have created feminist collectives to have sexual violence and other issues related to gender-based violence added to the agenda.
Dr. Drezett said it’s very unlikely that efforts made during a degree program are going to succeed in preventing students who are prone to commit sexual violence from engaging in such behavior. “We’re talking about gender-specific lessons, where discussions about gender-based violence should be started much, much earlier – parents talking to their children, teachers talking to their pupils.” He also doesn’t believe that the molesters are dissuaded by the fact that these accusations get publicized in the media. “If they were, the Roger Abdelmassih case would have done away with the problem.”
On the other hand, Dr. Drezett suggested, publicizing these stories can help to bring very positive issues out into the open. What the Bezerra case made clear was that laws were not followed and rights were not protected. An environment was thus created in which the sexual crime could be perpetrated, with nurses coming to suspect acts of obstetric violence, such as use of sedation, which prevented the woman from having skin-to-skin contact with the newborn and from breastfeeding within the first few hours of birth – two clinical practices that are recommended the world over.
“Health care professionals who act properly, in accordance with best practices for interacting with others and performing daily duties, at all times, in public or private practice – they remove themselves from situations like those described in the Bezerra case; they don’t practice medicine in a reckless manner,” said Dr. Drezett.
Another negative aspect of all this, he said, is that the suspicion and wariness that patients feel may spread far and wide. “Among my colleagues are anesthetists and anesthesiologists with impeccable ethical and professional records. They are very upset that people are now regarding them with doubt and uncertainty. We need to make it clear that those horrifying cases are the exceptions, not the rule,” he said. There is also a need to correct the misconception that such abuse is always in some way associated with obstetrics and gynecology.
“This is not true. These incidents can happen in any doctor’s office. It all depends on the physician – whether he or she has designs on committing a criminal act,” Dr. Drezett noted. He did point out that there are few sexual molesters among health care professionals, though there are numerous cases. Yet this in no way diminishes the seriousness of the incidents. “Of course, we’re speaking again about the exceptions, but in my experience of treating victims, I’ve seen, for example, more cases where it’s been a police officer, not a physician, committing an act of sexual violence against a woman,” he stated.
The nurses and nurse technicians at São João do Meriti Hospital who reported the abuser acted very assertively. If they hadn’t gathered the evidence to back up their accusations, it’s possible that the physician wouldn’t have been caught in the act and that the case would have taken a different course – including pressure being put on them and their becoming the target of retaliation.
A version of this article first appeared on Medscape.com. This article was translated from the Medscape Portuguese edition.
After ‘a Lot of Doors Shut in Our Face,’ Crusading Couple Celebrate Passage of Burn Pit Bill
The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.
Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.
Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.
Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.
“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”
The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.
Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.
When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.
He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.
In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.
Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.
Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.
For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.
“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.
As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”
It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.
“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.
“There were a lot of doors shut in our face,” Rosie said.
While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.
The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.
She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.
The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.
Related Links
- Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
- Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
- Role Reversal: Covid Increases Ranks of Child Caregivers
Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.
“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.
But just as with the 9/11 legislation, many in Congress weren’t that interested.
“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”
Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.
Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.
Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.
“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.
Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.
Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.
“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”
For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.
“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”
Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.
“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”
KHN reporter Heidi de Marco contributed to this article.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.
Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.
Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.
Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.
“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”
The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.
Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.
When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.
He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.
In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.
Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.
Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.
For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.
“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.
As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”
It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.
“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.
“There were a lot of doors shut in our face,” Rosie said.
While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.
The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.
She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.
The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.
Related Links
- Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
- Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
- Role Reversal: Covid Increases Ranks of Child Caregivers
Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.
“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.
But just as with the 9/11 legislation, many in Congress weren’t that interested.
“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”
Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.
Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.
Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.
“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.
Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.
Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.
“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”
For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.
“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”
Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.
“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”
KHN reporter Heidi de Marco contributed to this article.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.
Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.
Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.
Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.
“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”
The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.
Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.
When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.
He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.
In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.
Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.
Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.
For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.
“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.
As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”
It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.
“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.
“There were a lot of doors shut in our face,” Rosie said.
While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.
The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.
She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.
The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.
Related Links
- Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
- Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
- Role Reversal: Covid Increases Ranks of Child Caregivers
Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.
“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.
But just as with the 9/11 legislation, many in Congress weren’t that interested.
“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”
Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.
Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.
Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.
“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.
Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.
Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.
“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”
For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.
“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”
Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.
“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”
KHN reporter Heidi de Marco contributed to this article.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Vitamin D supplements during pregnancy may protect infants from atopic eczema
according to results of a clinical trial.
“Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on risk of infantile atopic eczema, with the effect only seen in infants that were breastfed for more than 1 month,” lead study author Sarah El-Heis, MRCP, DM, and colleagues wrote.
“The findings support a developmental influence on infantile atopic eczema and point to gestational cholecalciferol supplementation as a preventive strategy to reduce the burden of atopic eczema during infancy,” Dr. El-Heis, an academic clinical lecturer in dermatology at the Medical Research Council Lifecourse Epidemiology Center of the University of Southampton (England), said in a presentation at the annual meeting of the Society for Investigative Dermatology.
The study also was published in the British Journal of Dermatology.
Dr. El-Heis and colleagues analyzed data from one of the three U.K. study sites involved in the double-blind Maternal Vitamin D Osteoporosis Study (MAVIDOS), which enrolled participants between 2008 and 2014.
The women enrolled at the University of Southampton site were of age 18 or older, and had a singleton pregnancy. Serum 25-hydroxy vitamin D (25[OH]D) levels were 25-100 nmol/L, and calcium levels were less than 2.75 mmol/L.
Those who had metabolic bone disease, kidney stones, hyperparathyroidism, or hypercalciuria or who were taking more than 400 IU/day of vitamin D supplements or medication known to interfere with fetal growth or whose fetus had a major anomaly were excluded.
The study included 1,134 women. Half of the participants were randomly assigned to receive cholecalciferol 1,000 IU/day from around 14 weeks’ gestation until delivery, and half were assigned to receive placebo. Their babies were assessed for atopic eczema at 12, 24, and 48 months of age.
The maternal and infant characteristics were similar in both groups, but the treatment group tended to breastfeed longer.
Infants appear to be protected up to 1 year of age
Using logistic regression, the researchers analyzed links between maternal cholecalciferol 1,000 IU/day supplements or placebo and atopic eczema risk in their offspring.
After adjustments for breastfeeding duration, among the 636 infants assessed at 12 months, those whose mothers received cholecalciferol had lower odds ratios of atopic eczema than those whose mothers received placebo (OR, 0.55; 95% confidence interval, 0.32-0.97).
The risk of atopic eczema at 12 months was reduced only for children in the treatment group who were breastfed longer than 1 month (OR, 0.48; 95% CI, 0.24-0.94), further analysis showed. Those who were breastfed for less than 1 month showed no reduced risk.
The combined effect of vitamin D and breastfeeding for longer than 1 month weakened after 1 year and was not statistically significant among the 611 children assessed at 24 months and the 450 children assessed at 48 months. The ORs of atopic eczema in the treatment group and in the control group increased to 0.76 (95% CI, 0.47-1.23) and 0.75 (95% CI, 0.37-1.52), respectively.
At baseline, the mean maternal serum 25(OH)D levels in the treatment group (46.0 nmol/L) and in the control group (44.7 nmol/L) were similar. But by late pregnancy, maternal serum 25(OH)D levels in the treatment group were higher (67.4 nmol/L) than in the control group (42.4 nmol/L).
The authors note that strengths of the study include its design, the uniformity of criteria used to diagnose atopic eczema, and the similarity of both pregnant groups in their intake of vitamin D during the study.
Limitations included the lack of ultraviolet B light exposure data, the lack of non-White women in the study, the lack of measurement of cord blood and offspring 25(OH)D levels, and the exclusion of women with baseline 25(OH)D concentrations less than 25 nmol/L.
“This is an interesting study that brings up the possibility that maternal factors during pregnancy may impact atopic dermatitis,” Kalyani S. Marathe, MD, MPH, the director of the division of dermatology at Cincinnati Children’s Hospital Medical Center, told this news organization.
The results are mixed, though, she noted.
“While some impact on the risk of eczema is seen at 1 year of age, that protective effect is gone by 2 years and 4 years,” Dr. Marathe, who was not involved in the study, said in an email. “So if maternal supplementation does improve eczema, the effect is not long-lasting.
“The other complicating factor is that the babies who showed reduction in eczema were also the ones who were breastfed longer than 1 month,” she added. “We know that breastfeeding is associated with several factors, including socioeconomic status, so it is difficult to tease out the relationships here.
“Vitamin D has become a very hot topic lately and seems to have protective effects in many areas of health care,” Dr. Marathe said. “These results may motivate pregnant women to be compliant with their prenatal vitamins that contain the amount of vitamin D studied here.”
The study received grant support. Several authors disclosed financial relationships with pharmaceutical and nutritional products industries. Dr. El-Heis and Dr. Marathe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to results of a clinical trial.
“Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on risk of infantile atopic eczema, with the effect only seen in infants that were breastfed for more than 1 month,” lead study author Sarah El-Heis, MRCP, DM, and colleagues wrote.
“The findings support a developmental influence on infantile atopic eczema and point to gestational cholecalciferol supplementation as a preventive strategy to reduce the burden of atopic eczema during infancy,” Dr. El-Heis, an academic clinical lecturer in dermatology at the Medical Research Council Lifecourse Epidemiology Center of the University of Southampton (England), said in a presentation at the annual meeting of the Society for Investigative Dermatology.
The study also was published in the British Journal of Dermatology.
Dr. El-Heis and colleagues analyzed data from one of the three U.K. study sites involved in the double-blind Maternal Vitamin D Osteoporosis Study (MAVIDOS), which enrolled participants between 2008 and 2014.
The women enrolled at the University of Southampton site were of age 18 or older, and had a singleton pregnancy. Serum 25-hydroxy vitamin D (25[OH]D) levels were 25-100 nmol/L, and calcium levels were less than 2.75 mmol/L.
Those who had metabolic bone disease, kidney stones, hyperparathyroidism, or hypercalciuria or who were taking more than 400 IU/day of vitamin D supplements or medication known to interfere with fetal growth or whose fetus had a major anomaly were excluded.
The study included 1,134 women. Half of the participants were randomly assigned to receive cholecalciferol 1,000 IU/day from around 14 weeks’ gestation until delivery, and half were assigned to receive placebo. Their babies were assessed for atopic eczema at 12, 24, and 48 months of age.
The maternal and infant characteristics were similar in both groups, but the treatment group tended to breastfeed longer.
Infants appear to be protected up to 1 year of age
Using logistic regression, the researchers analyzed links between maternal cholecalciferol 1,000 IU/day supplements or placebo and atopic eczema risk in their offspring.
After adjustments for breastfeeding duration, among the 636 infants assessed at 12 months, those whose mothers received cholecalciferol had lower odds ratios of atopic eczema than those whose mothers received placebo (OR, 0.55; 95% confidence interval, 0.32-0.97).
The risk of atopic eczema at 12 months was reduced only for children in the treatment group who were breastfed longer than 1 month (OR, 0.48; 95% CI, 0.24-0.94), further analysis showed. Those who were breastfed for less than 1 month showed no reduced risk.
The combined effect of vitamin D and breastfeeding for longer than 1 month weakened after 1 year and was not statistically significant among the 611 children assessed at 24 months and the 450 children assessed at 48 months. The ORs of atopic eczema in the treatment group and in the control group increased to 0.76 (95% CI, 0.47-1.23) and 0.75 (95% CI, 0.37-1.52), respectively.
At baseline, the mean maternal serum 25(OH)D levels in the treatment group (46.0 nmol/L) and in the control group (44.7 nmol/L) were similar. But by late pregnancy, maternal serum 25(OH)D levels in the treatment group were higher (67.4 nmol/L) than in the control group (42.4 nmol/L).
The authors note that strengths of the study include its design, the uniformity of criteria used to diagnose atopic eczema, and the similarity of both pregnant groups in their intake of vitamin D during the study.
Limitations included the lack of ultraviolet B light exposure data, the lack of non-White women in the study, the lack of measurement of cord blood and offspring 25(OH)D levels, and the exclusion of women with baseline 25(OH)D concentrations less than 25 nmol/L.
“This is an interesting study that brings up the possibility that maternal factors during pregnancy may impact atopic dermatitis,” Kalyani S. Marathe, MD, MPH, the director of the division of dermatology at Cincinnati Children’s Hospital Medical Center, told this news organization.
The results are mixed, though, she noted.
“While some impact on the risk of eczema is seen at 1 year of age, that protective effect is gone by 2 years and 4 years,” Dr. Marathe, who was not involved in the study, said in an email. “So if maternal supplementation does improve eczema, the effect is not long-lasting.
“The other complicating factor is that the babies who showed reduction in eczema were also the ones who were breastfed longer than 1 month,” she added. “We know that breastfeeding is associated with several factors, including socioeconomic status, so it is difficult to tease out the relationships here.
“Vitamin D has become a very hot topic lately and seems to have protective effects in many areas of health care,” Dr. Marathe said. “These results may motivate pregnant women to be compliant with their prenatal vitamins that contain the amount of vitamin D studied here.”
The study received grant support. Several authors disclosed financial relationships with pharmaceutical and nutritional products industries. Dr. El-Heis and Dr. Marathe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to results of a clinical trial.
“Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on risk of infantile atopic eczema, with the effect only seen in infants that were breastfed for more than 1 month,” lead study author Sarah El-Heis, MRCP, DM, and colleagues wrote.
“The findings support a developmental influence on infantile atopic eczema and point to gestational cholecalciferol supplementation as a preventive strategy to reduce the burden of atopic eczema during infancy,” Dr. El-Heis, an academic clinical lecturer in dermatology at the Medical Research Council Lifecourse Epidemiology Center of the University of Southampton (England), said in a presentation at the annual meeting of the Society for Investigative Dermatology.
The study also was published in the British Journal of Dermatology.
Dr. El-Heis and colleagues analyzed data from one of the three U.K. study sites involved in the double-blind Maternal Vitamin D Osteoporosis Study (MAVIDOS), which enrolled participants between 2008 and 2014.
The women enrolled at the University of Southampton site were of age 18 or older, and had a singleton pregnancy. Serum 25-hydroxy vitamin D (25[OH]D) levels were 25-100 nmol/L, and calcium levels were less than 2.75 mmol/L.
Those who had metabolic bone disease, kidney stones, hyperparathyroidism, or hypercalciuria or who were taking more than 400 IU/day of vitamin D supplements or medication known to interfere with fetal growth or whose fetus had a major anomaly were excluded.
The study included 1,134 women. Half of the participants were randomly assigned to receive cholecalciferol 1,000 IU/day from around 14 weeks’ gestation until delivery, and half were assigned to receive placebo. Their babies were assessed for atopic eczema at 12, 24, and 48 months of age.
The maternal and infant characteristics were similar in both groups, but the treatment group tended to breastfeed longer.
Infants appear to be protected up to 1 year of age
Using logistic regression, the researchers analyzed links between maternal cholecalciferol 1,000 IU/day supplements or placebo and atopic eczema risk in their offspring.
After adjustments for breastfeeding duration, among the 636 infants assessed at 12 months, those whose mothers received cholecalciferol had lower odds ratios of atopic eczema than those whose mothers received placebo (OR, 0.55; 95% confidence interval, 0.32-0.97).
The risk of atopic eczema at 12 months was reduced only for children in the treatment group who were breastfed longer than 1 month (OR, 0.48; 95% CI, 0.24-0.94), further analysis showed. Those who were breastfed for less than 1 month showed no reduced risk.
The combined effect of vitamin D and breastfeeding for longer than 1 month weakened after 1 year and was not statistically significant among the 611 children assessed at 24 months and the 450 children assessed at 48 months. The ORs of atopic eczema in the treatment group and in the control group increased to 0.76 (95% CI, 0.47-1.23) and 0.75 (95% CI, 0.37-1.52), respectively.
At baseline, the mean maternal serum 25(OH)D levels in the treatment group (46.0 nmol/L) and in the control group (44.7 nmol/L) were similar. But by late pregnancy, maternal serum 25(OH)D levels in the treatment group were higher (67.4 nmol/L) than in the control group (42.4 nmol/L).
The authors note that strengths of the study include its design, the uniformity of criteria used to diagnose atopic eczema, and the similarity of both pregnant groups in their intake of vitamin D during the study.
Limitations included the lack of ultraviolet B light exposure data, the lack of non-White women in the study, the lack of measurement of cord blood and offspring 25(OH)D levels, and the exclusion of women with baseline 25(OH)D concentrations less than 25 nmol/L.
“This is an interesting study that brings up the possibility that maternal factors during pregnancy may impact atopic dermatitis,” Kalyani S. Marathe, MD, MPH, the director of the division of dermatology at Cincinnati Children’s Hospital Medical Center, told this news organization.
The results are mixed, though, she noted.
“While some impact on the risk of eczema is seen at 1 year of age, that protective effect is gone by 2 years and 4 years,” Dr. Marathe, who was not involved in the study, said in an email. “So if maternal supplementation does improve eczema, the effect is not long-lasting.
“The other complicating factor is that the babies who showed reduction in eczema were also the ones who were breastfed longer than 1 month,” she added. “We know that breastfeeding is associated with several factors, including socioeconomic status, so it is difficult to tease out the relationships here.
“Vitamin D has become a very hot topic lately and seems to have protective effects in many areas of health care,” Dr. Marathe said. “These results may motivate pregnant women to be compliant with their prenatal vitamins that contain the amount of vitamin D studied here.”
The study received grant support. Several authors disclosed financial relationships with pharmaceutical and nutritional products industries. Dr. El-Heis and Dr. Marathe reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SID 2022
Prolonged Drug-Induced Hypersensitivity Syndrome/DRESS With Alopecia Areata and Autoimmune Thyroiditis
Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.
Case Presentation
A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.
Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.
The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.
Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.
Discussion
DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5
The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8
DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.
Treatment
For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11
A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12
The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10
Conclusions
DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.
1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org
2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006
3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013
4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934
5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501
6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879
7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942
8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053
9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770
10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017
11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006
12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048
13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001
14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713
Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.
Case Presentation
A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.
Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.
The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.
Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.
Discussion
DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5
The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8
DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.
Treatment
For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11
A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12
The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10
Conclusions
DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.
Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.
Case Presentation
A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.
Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.
The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.
Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.
Discussion
DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5
The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8
DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.
Treatment
For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11
A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12
The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10
Conclusions
DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.
1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org
2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006
3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013
4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934
5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501
6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879
7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942
8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053
9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770
10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017
11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006
12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048
13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001
14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713
1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org
2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006
3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013
4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934
5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501
6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879
7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942
8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053
9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770
10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017
11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006
12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048
13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001
14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713