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Doctors treat osteoporosis with hormone therapy against guidelines
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.
According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.
Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
Women’s Health Initiative findings
The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.
The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.
Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.
“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
Hormone therapy’s complex history
HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.
While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.
Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.
“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”
Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.
It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
Today’s use of HT in women with osteoporosis
Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.
“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.
“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.
“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.
Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.
“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.
According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.
“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
Additional scenarios when doctors may advise HT
“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.
“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”
Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.
“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”
“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.
“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”
Dr. Roberts added that HT would be more of a niche drug.
“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”
Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other experts interviewed for this piece reported no conflicts.
New ACC guidance on cardiovascular consequences of COVID-19
The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.
The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.
The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.
“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”
The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine.
“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
Myocarditis
The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.
It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.
The document makes the following recommendations in regard to COVID-related myocarditis:
When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.
Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.
Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.
As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.
The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.
But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.
In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
Long COVID
The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.
Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.
Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”
The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:
PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.
PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.
The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.
For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.
Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.
Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.
Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.
Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
Return to play for athletes
The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.
But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.
They make the following recommendations:
- For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
- For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
- Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
- For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
- For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.
Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.
Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.
The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.
“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.
The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.
A version of this article first appeared on Medscape.com.
The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.
The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.
The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.
“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”
The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine.
“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
Myocarditis
The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.
It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.
The document makes the following recommendations in regard to COVID-related myocarditis:
When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.
Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.
Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.
As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.
The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.
But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.
In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
Long COVID
The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.
Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.
Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”
The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:
PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.
PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.
The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.
For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.
Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.
Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.
Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.
Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
Return to play for athletes
The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.
But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.
They make the following recommendations:
- For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
- For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
- Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
- For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
- For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.
Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.
Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.
The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.
“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.
The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.
A version of this article first appeared on Medscape.com.
The American College of Cardiology has issued an expert consensus clinical guidance document for the evaluation and management of adults with key cardiovascular consequences of COVID-19.
The document makes recommendations on how to evaluate and manage COVID-associated myocarditis and long COVID and gives advice on resumption of exercise following COVID-19 infection.
The clinical guidance was published online March 16 in the Journal of the American College of Cardiology.
“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, cochair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and noncompetitive athletes.”
The authors of the guidance note that COVID-19 can be associated with various abnormalities in cardiac testing and a wide range of cardiovascular complications. For some patients, cardiac symptoms such as chest pain, shortness of breath, fatigue, and palpitations persist, lasting months after the initial illness, and evidence of myocardial injury has also been observed in both symptomatic and asymptomatic individuals, as well as after receipt of the COVID-19 mRNA vaccine.
“For clinicians treating these individuals, a growing number of questions exist related to evaluation and management of these conditions, as well as safe resumption of physical activity,” they say. This report is intended to provide practical guidance on these issues.
Myocarditis
The report states that myocarditis has been recognized as a rare but serious complication of SARS-CoV-2 infection as well as COVID-19 mRNA vaccination.
It defines myocarditis as: 1.cardiac symptoms such as chest pain, dyspnea, palpitations, or syncope; 2. elevated cardiac troponin; and 3. abnormal electrocardiographic, echocardiographic, cardiac MRI, and/or histopathologic findings on biopsy.
The document makes the following recommendations in regard to COVID-related myocarditis:
When there is increased suspicion for cardiac involvement with COVID-19, initial testing should consist of an ECG, measurement of cardiac troponin, and an echocardiogram. Cardiology consultation is recommended for those with a rising cardiac troponin and/or echocardiographic abnormalities. Cardiac MRI is recommended in hemodynamically stable patients with suspected myocarditis.
Hospitalization is recommended for patients with definite myocarditis, ideally at an advanced heart failure center. Patients with fulminant myocarditis should be managed at centers with an expertise in advanced heart failure, mechanical circulatory support, and other advanced therapies.
Patients with myocarditis and COVID-19 pneumonia (with an ongoing need for supplemental oxygen) should be treated with corticosteroids. For patients with suspected pericardial involvement, treatment with NSAIDs, colchicine, and/or prednisone is reasonable. Intravenous corticosteroids may be considered in those with suspected or confirmed COVID-19 myocarditis with hemodynamic compromise or MIS-A (multisystem inflammatory syndrome in adults). Empiric use of corticosteroids may also be considered in those with biopsy evidence of severe myocardial infiltrates or fulminant myocarditis, balanced against infection risk.
As appropriate, guideline-directed medical therapy for heart failure should be initiated and continued after discharge.
The document notes that myocarditis following COVID-19 mRNA vaccination is rare, with highest rates seen in young males after the second vaccine dose. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged 30 and older. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively.
But the report says that COVID-19 vaccination is associated with “a very favorable benefit-to-risk ratio” for all age and sex groups evaluated thus far.
In general, vaccine-associated myocarditis should be diagnosed, categorized, and treated in a manner analogous to myocarditis following SARS-CoV-2 infection, the guidance advises.
Long COVID
The document refers to long COVID as postacute sequelae of SARS-CoV-2 infection (PASC), and reports that this condition is experienced by up to 10%-30% of infected individuals. It is defined by a constellation of new, returning, or persistent health problems experienced by individuals 4 or more weeks after COVID-19 infection.
Although individuals with this condition may experience wide-ranging symptoms, the symptoms that draw increased attention to the cardiovascular system include tachycardia, exercise intolerance, chest pain, and shortness of breath.
Nicole Bhave, MD, cochair of the expert consensus decision pathway, says: “There appears to be a ‘downward spiral’ for long-COVID patients. Fatigue and decreased exercise capacity lead to diminished activity and bed rest, in turn leading to worsening symptoms and decreased quality of life.” She adds that “the writing committee recommends a basic cardiopulmonary evaluation performed up front to determine if further specialty care and formalized medical therapy is needed for these patients.”
The authors propose two terms to better understand potential etiologies for those with cardiovascular symptoms:
PASC-CVD, or PASC-cardiovascular disease, refers to a broad group of cardiovascular conditions (including myocarditis) that manifest at least 4 weeks after COVID-19 infection.
PASC-CVS, or PASC-cardiovascular syndrome, includes a wide range of cardiovascular symptoms without objective evidence of cardiovascular disease following standard diagnostic testing.
The document makes the following recommendations for the management of PASC-CVD and PASC-CVS.
For patients with cardiovascular symptoms and suspected PASC, the authors suggest that a reasonable initial testing approach includes basic laboratory testing, including cardiac troponin, an ECG, an echocardiogram, an ambulatory rhythm monitor, chest imaging, and/or pulmonary function tests.
Cardiology consultation is recommended for patients with PASC who have abnormal cardiac test results, known cardiovascular disease with new or worsening symptoms, documented cardiac complications during SARS-CoV-2 infection, and/or persistent cardiopulmonary symptoms that are not otherwise explained.
Recumbent or semirecumbent exercise (for example, rowing, swimming, or cycling) is recommended initially for PASC-CVS patients with tachycardia, exercise/orthostatic intolerance, and/or deconditioning, with transition to upright exercise as orthostatic intolerance improves. Exercise duration should also be short (5-10 minutes/day) initially, with gradual increases as functional capacity improves.
Salt and fluid loading represent nonpharmacologic interventions that may provide symptomatic relief for patients with tachycardia, palpitations, and/or orthostatic hypotension.
Beta-blockers, nondihydropyridine calcium-channel blockers, ivabradine, fludrocortisone, and midodrine may be used empirically as well.
Return to play for athletes
The authors note that concerns about possible cardiac injury after COVID-19 fueled early apprehension regarding the safety of competitive sports for athletes recovering from the infection.
But they say that subsequent data from large registries have demonstrated an overall low prevalence of clinical myocarditis, without a rise in the rate of adverse cardiac events. Based on this, updated guidance is provided with a practical, evidence-based framework to guide resumption of athletics and intense exercise training.
They make the following recommendations:
- For athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms (chest pain, shortness of breath, palpitations, lightheadedness) or those requiring hospitalization with increased suspicion for cardiac involvement, further evaluation with triad testing – an ECG, measurement of cardiac troponin, and an echocardiogram – should be performed.
- For those with abnormal test results, further evaluation with cardiac MRI should be considered. Individuals diagnosed with clinical myocarditis should abstain from exercise for 3-6 months.
- Cardiac testing is not recommended for asymptomatic individuals following COVID-19 infection. Individuals should abstain from training for 3 days to ensure that symptoms do not develop.
- For those with mild or moderate noncardiopulmonary symptoms (fever, lethargy, muscle aches), training may resume after symptom resolution.
- For those with remote infection (≥3 months) without ongoing cardiopulmonary symptoms, a gradual increase in exercise is recommended without the need for cardiac testing.
Based on the low prevalence of myocarditis observed in competitive athletes with COVID-19, the authors note that these recommendations can be reasonably applied to high-school athletes (aged 14 and older) along with adult recreational exercise enthusiasts.
Future study is needed, however, to better understand how long cardiac abnormalities persist following COVID-19 infection and the role of exercise training in long COVID.
The authors conclude that the current guidance is intended to help clinicians understand not only when testing may be warranted, but also when it is not.
“Given that it reflects the current state of knowledge through early 2022, it is anticipated that recommendations will change over time as our understanding evolves,” they say.
The 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19: Myocarditis, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and Return to Play will be discussed in a session at the American College of Cardiology’s annual scientific session meeting in Washington in April.
A version of this article first appeared on Medscape.com.
A 31-year-old female presented with a burning rash on upper arms, groin, and axillae
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
Betamethasone cream did not alleviate symptoms.
Gene therapy for hemophilia A: `Truly transformative and liberating’
Significant results were seen 1 year after receiving a single intravenous infusion of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), investigators from the international GENEr8-1 trial reported in the New England Journal of Medicine.
‘Truly transformative and liberating’
“If approved, this first-generation gene therapy would offer a new choice for care that could be truly transformative and liberating for eligible men with hemophilia,” writes Courtney D. Thornburg, from the Hemophilia and Thrombosis Treatment Center at Rady Children’s Hospital, San Diego, in an accompanying editorial.
Hemophilia A is an X-linked bleeding disorder caused by mutations in the gene encoding for coagulation factor VIII. Although rare, it is nevertheless the most common type, affecting about 12 per 100,000. Hemophilia B affects about 3.7 per 100,000.
The current treatment for hemophilia A is prophylactic infusions of factor VIII, often given three times per week.
With the gene therapy, such a patient could avoid at least 150 intravenous infusions of prophylactic factor in the span of a year, and have zero bleeds, Dr. Thornburg noted.
Valoctocogene roxaparvovec is an adeno-associated virus 5-based gene therapy vector that expresses a human factor VIII coding sequence, and is designed to correct the central genetic defect in hemophilia A.
Results from the phase 3 open-label trial show that it was associated with improved endogenous clotting factor production, and also a significant decrease in bleeding.
At 49-52 weeks of follow-up, 132 patients in a modified intention-to-treat analysis had a mean increase in factor VIII activity levels of 41.9 IU/dL (P < .001).
In a subgroup of 112 patients, the mean annualized factor concentrate use at 4 weeks decreased by 98.6%, and annualized rates of treated bleeding declined by 83.8% (P < .001 for both comparisons).
“Valoctocogene roxaparvovec gene transfer for severe hemophilia A provided significant increases in factor VIII activity, with reduced bleeding and factor VIII use for most participants over a period of up to 2 years,” conclude the investigators, led by Margareth C. Ozelo, MD, PhD, from the University of Campinas (Brazil).
“We are very enthusiastic about the results of this phase 3 clinical trial,” Dr. Ozelo commented to this news organization.
“It is important to recognize the clinical benefit achieved so far with treatment. During the first year, 90% of study participants had either zero treated bleeds or fewer treated bleeds post infusion than with factor VIII prophylaxis,” she said. “In addition, most of the study participants, including those from the phase 1/2 clinical trial, in the 5-year follow-up remain free of the use of additional prophylactic treatments.”
One issue that remains unanswered is how long the effects may last.
Valoctocogene roxaparvovec is a one-time infusion, she explained. “At least for now, redosing with the same AAV vector is not an option due to the immune response induced.”
“The durability of therapeutic response is one of the critical issues involving this new treatment for hemophilia. Currently, we cannot predict how long the transgene expression will last,” she added.
In the study, Dr. Ozelo and colleagues noted that “expression of the transferred gene appears to decline over time; further study is needed to address whether repeat treatment will be necessary or possible.”
Editorialist Dr. Thornburg touched on this point in an interview with this news organization.
Complete elimination of factor VIII replacement therapy is an ambitious goal, but gene therapy could obviate the need for prophylaxis in a substantial proportion of patients, she said. “Any increase of about 3%-5% in endogenous factor VIII production would eliminate the need for regular preventive treatments, either with regular factor or nonfactor replacements.
“How long that will be sustained is an open question,” she added. “With hemophilia B [factor IX deficiency] we have longer-term data showing quite good sustainability of the treatment, but I think it’s still an open question for hemophilia A.”
Dr. Thornburg also noted that further studies are needed to find similar therapies to benefit women and children with hemophilia, as well as for patients with factor VIII inhibitors, those with immunity to adenoviral vectors, and patients with hemophilia and concomitant liver disease or HIV infection.
GENEr8-1 study details and results
The trial was conducted in men 18 and older with severe congenital hemophilia A who had received prophylaxis with factor VIII concentrates for at least 1 year and were negative for factor VIII inhibitors.
The patient sample included 20 men enrolled directly, and 110 participants in a prospective noninterventional study of bleeding episodes, factor VIII infusions, and patient-reported outcomes in individuals with severe hemophilia A.
Participants received one infusion of valoctocogene roxaparvovec, at a dose of 6x1013 vector genomes per kilogram of body weight.
They remained on factor VIII prophylaxis for 4 weeks after the infusion of the gene therapy product, but after that factor VIII was used on an as-needed basis.
A total of 134 patients received an infusion and were included in the safety analysis. Two patients who were HIV positive were excluded from the modified intention-to-treat efficacy analysis.
As noted above, the trial met its primary efficacy endpoint of change from baseline in factor VIII activity 49-52 weeks after infusion, and the secondary endpoints of change from baseline to after week 4 in annualized use of factor VIII concentrate and the annualized number of treated bleeding episodes.
The most common adverse event was an elevation in alanine aminotransferase levels, the investigators noted.
These elevations in ALT levels, which have also been seen with gene therapy for hemophilia B, occurred in 85.8% of patients and could be safely managed with immunosuppressants, the authors commented.
Other common adverse events were headache, nausea, and elevations in aspartate aminotransferase levels, each occurring in slightly more than one third of patients.
“Overall, the risk-benefit profile appears favorable,” the team commented.
The study was supported by BioMarin Pharmaceutical. Dr. Ozelo disclosed grant support from the company. Dr. Thornburg disclosed serving as a consultant to BioMarin and others.
A version of this article first appeared on Medscape.com.
Significant results were seen 1 year after receiving a single intravenous infusion of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), investigators from the international GENEr8-1 trial reported in the New England Journal of Medicine.
‘Truly transformative and liberating’
“If approved, this first-generation gene therapy would offer a new choice for care that could be truly transformative and liberating for eligible men with hemophilia,” writes Courtney D. Thornburg, from the Hemophilia and Thrombosis Treatment Center at Rady Children’s Hospital, San Diego, in an accompanying editorial.
Hemophilia A is an X-linked bleeding disorder caused by mutations in the gene encoding for coagulation factor VIII. Although rare, it is nevertheless the most common type, affecting about 12 per 100,000. Hemophilia B affects about 3.7 per 100,000.
The current treatment for hemophilia A is prophylactic infusions of factor VIII, often given three times per week.
With the gene therapy, such a patient could avoid at least 150 intravenous infusions of prophylactic factor in the span of a year, and have zero bleeds, Dr. Thornburg noted.
Valoctocogene roxaparvovec is an adeno-associated virus 5-based gene therapy vector that expresses a human factor VIII coding sequence, and is designed to correct the central genetic defect in hemophilia A.
Results from the phase 3 open-label trial show that it was associated with improved endogenous clotting factor production, and also a significant decrease in bleeding.
At 49-52 weeks of follow-up, 132 patients in a modified intention-to-treat analysis had a mean increase in factor VIII activity levels of 41.9 IU/dL (P < .001).
In a subgroup of 112 patients, the mean annualized factor concentrate use at 4 weeks decreased by 98.6%, and annualized rates of treated bleeding declined by 83.8% (P < .001 for both comparisons).
“Valoctocogene roxaparvovec gene transfer for severe hemophilia A provided significant increases in factor VIII activity, with reduced bleeding and factor VIII use for most participants over a period of up to 2 years,” conclude the investigators, led by Margareth C. Ozelo, MD, PhD, from the University of Campinas (Brazil).
“We are very enthusiastic about the results of this phase 3 clinical trial,” Dr. Ozelo commented to this news organization.
“It is important to recognize the clinical benefit achieved so far with treatment. During the first year, 90% of study participants had either zero treated bleeds or fewer treated bleeds post infusion than with factor VIII prophylaxis,” she said. “In addition, most of the study participants, including those from the phase 1/2 clinical trial, in the 5-year follow-up remain free of the use of additional prophylactic treatments.”
One issue that remains unanswered is how long the effects may last.
Valoctocogene roxaparvovec is a one-time infusion, she explained. “At least for now, redosing with the same AAV vector is not an option due to the immune response induced.”
“The durability of therapeutic response is one of the critical issues involving this new treatment for hemophilia. Currently, we cannot predict how long the transgene expression will last,” she added.
In the study, Dr. Ozelo and colleagues noted that “expression of the transferred gene appears to decline over time; further study is needed to address whether repeat treatment will be necessary or possible.”
Editorialist Dr. Thornburg touched on this point in an interview with this news organization.
Complete elimination of factor VIII replacement therapy is an ambitious goal, but gene therapy could obviate the need for prophylaxis in a substantial proportion of patients, she said. “Any increase of about 3%-5% in endogenous factor VIII production would eliminate the need for regular preventive treatments, either with regular factor or nonfactor replacements.
“How long that will be sustained is an open question,” she added. “With hemophilia B [factor IX deficiency] we have longer-term data showing quite good sustainability of the treatment, but I think it’s still an open question for hemophilia A.”
Dr. Thornburg also noted that further studies are needed to find similar therapies to benefit women and children with hemophilia, as well as for patients with factor VIII inhibitors, those with immunity to adenoviral vectors, and patients with hemophilia and concomitant liver disease or HIV infection.
GENEr8-1 study details and results
The trial was conducted in men 18 and older with severe congenital hemophilia A who had received prophylaxis with factor VIII concentrates for at least 1 year and were negative for factor VIII inhibitors.
The patient sample included 20 men enrolled directly, and 110 participants in a prospective noninterventional study of bleeding episodes, factor VIII infusions, and patient-reported outcomes in individuals with severe hemophilia A.
Participants received one infusion of valoctocogene roxaparvovec, at a dose of 6x1013 vector genomes per kilogram of body weight.
They remained on factor VIII prophylaxis for 4 weeks after the infusion of the gene therapy product, but after that factor VIII was used on an as-needed basis.
A total of 134 patients received an infusion and were included in the safety analysis. Two patients who were HIV positive were excluded from the modified intention-to-treat efficacy analysis.
As noted above, the trial met its primary efficacy endpoint of change from baseline in factor VIII activity 49-52 weeks after infusion, and the secondary endpoints of change from baseline to after week 4 in annualized use of factor VIII concentrate and the annualized number of treated bleeding episodes.
The most common adverse event was an elevation in alanine aminotransferase levels, the investigators noted.
These elevations in ALT levels, which have also been seen with gene therapy for hemophilia B, occurred in 85.8% of patients and could be safely managed with immunosuppressants, the authors commented.
Other common adverse events were headache, nausea, and elevations in aspartate aminotransferase levels, each occurring in slightly more than one third of patients.
“Overall, the risk-benefit profile appears favorable,” the team commented.
The study was supported by BioMarin Pharmaceutical. Dr. Ozelo disclosed grant support from the company. Dr. Thornburg disclosed serving as a consultant to BioMarin and others.
A version of this article first appeared on Medscape.com.
Significant results were seen 1 year after receiving a single intravenous infusion of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), investigators from the international GENEr8-1 trial reported in the New England Journal of Medicine.
‘Truly transformative and liberating’
“If approved, this first-generation gene therapy would offer a new choice for care that could be truly transformative and liberating for eligible men with hemophilia,” writes Courtney D. Thornburg, from the Hemophilia and Thrombosis Treatment Center at Rady Children’s Hospital, San Diego, in an accompanying editorial.
Hemophilia A is an X-linked bleeding disorder caused by mutations in the gene encoding for coagulation factor VIII. Although rare, it is nevertheless the most common type, affecting about 12 per 100,000. Hemophilia B affects about 3.7 per 100,000.
The current treatment for hemophilia A is prophylactic infusions of factor VIII, often given three times per week.
With the gene therapy, such a patient could avoid at least 150 intravenous infusions of prophylactic factor in the span of a year, and have zero bleeds, Dr. Thornburg noted.
Valoctocogene roxaparvovec is an adeno-associated virus 5-based gene therapy vector that expresses a human factor VIII coding sequence, and is designed to correct the central genetic defect in hemophilia A.
Results from the phase 3 open-label trial show that it was associated with improved endogenous clotting factor production, and also a significant decrease in bleeding.
At 49-52 weeks of follow-up, 132 patients in a modified intention-to-treat analysis had a mean increase in factor VIII activity levels of 41.9 IU/dL (P < .001).
In a subgroup of 112 patients, the mean annualized factor concentrate use at 4 weeks decreased by 98.6%, and annualized rates of treated bleeding declined by 83.8% (P < .001 for both comparisons).
“Valoctocogene roxaparvovec gene transfer for severe hemophilia A provided significant increases in factor VIII activity, with reduced bleeding and factor VIII use for most participants over a period of up to 2 years,” conclude the investigators, led by Margareth C. Ozelo, MD, PhD, from the University of Campinas (Brazil).
“We are very enthusiastic about the results of this phase 3 clinical trial,” Dr. Ozelo commented to this news organization.
“It is important to recognize the clinical benefit achieved so far with treatment. During the first year, 90% of study participants had either zero treated bleeds or fewer treated bleeds post infusion than with factor VIII prophylaxis,” she said. “In addition, most of the study participants, including those from the phase 1/2 clinical trial, in the 5-year follow-up remain free of the use of additional prophylactic treatments.”
One issue that remains unanswered is how long the effects may last.
Valoctocogene roxaparvovec is a one-time infusion, she explained. “At least for now, redosing with the same AAV vector is not an option due to the immune response induced.”
“The durability of therapeutic response is one of the critical issues involving this new treatment for hemophilia. Currently, we cannot predict how long the transgene expression will last,” she added.
In the study, Dr. Ozelo and colleagues noted that “expression of the transferred gene appears to decline over time; further study is needed to address whether repeat treatment will be necessary or possible.”
Editorialist Dr. Thornburg touched on this point in an interview with this news organization.
Complete elimination of factor VIII replacement therapy is an ambitious goal, but gene therapy could obviate the need for prophylaxis in a substantial proportion of patients, she said. “Any increase of about 3%-5% in endogenous factor VIII production would eliminate the need for regular preventive treatments, either with regular factor or nonfactor replacements.
“How long that will be sustained is an open question,” she added. “With hemophilia B [factor IX deficiency] we have longer-term data showing quite good sustainability of the treatment, but I think it’s still an open question for hemophilia A.”
Dr. Thornburg also noted that further studies are needed to find similar therapies to benefit women and children with hemophilia, as well as for patients with factor VIII inhibitors, those with immunity to adenoviral vectors, and patients with hemophilia and concomitant liver disease or HIV infection.
GENEr8-1 study details and results
The trial was conducted in men 18 and older with severe congenital hemophilia A who had received prophylaxis with factor VIII concentrates for at least 1 year and were negative for factor VIII inhibitors.
The patient sample included 20 men enrolled directly, and 110 participants in a prospective noninterventional study of bleeding episodes, factor VIII infusions, and patient-reported outcomes in individuals with severe hemophilia A.
Participants received one infusion of valoctocogene roxaparvovec, at a dose of 6x1013 vector genomes per kilogram of body weight.
They remained on factor VIII prophylaxis for 4 weeks after the infusion of the gene therapy product, but after that factor VIII was used on an as-needed basis.
A total of 134 patients received an infusion and were included in the safety analysis. Two patients who were HIV positive were excluded from the modified intention-to-treat efficacy analysis.
As noted above, the trial met its primary efficacy endpoint of change from baseline in factor VIII activity 49-52 weeks after infusion, and the secondary endpoints of change from baseline to after week 4 in annualized use of factor VIII concentrate and the annualized number of treated bleeding episodes.
The most common adverse event was an elevation in alanine aminotransferase levels, the investigators noted.
These elevations in ALT levels, which have also been seen with gene therapy for hemophilia B, occurred in 85.8% of patients and could be safely managed with immunosuppressants, the authors commented.
Other common adverse events were headache, nausea, and elevations in aspartate aminotransferase levels, each occurring in slightly more than one third of patients.
“Overall, the risk-benefit profile appears favorable,” the team commented.
The study was supported by BioMarin Pharmaceutical. Dr. Ozelo disclosed grant support from the company. Dr. Thornburg disclosed serving as a consultant to BioMarin and others.
A version of this article first appeared on Medscape.com.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Dealing with life-threatening asthma attacks
In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.
“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.
“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.
The study was published online in the journal CHEST®.
Appropriate triage
Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.
Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1). A severe exacerbation is usually defined as a PEF or an FEV1 of less than 50%-60% of predicted normal values, the authors noted.
Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.
These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta2-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.
For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.
Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO2 requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”
Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
Ventilation in life-threatening asthma
Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.
Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.
Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.
“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV1 – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.
On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.
“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.
Dr. Garner and Dr. Long disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.
“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.
“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.
The study was published online in the journal CHEST®.
Appropriate triage
Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.
Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1). A severe exacerbation is usually defined as a PEF or an FEV1 of less than 50%-60% of predicted normal values, the authors noted.
Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.
These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta2-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.
For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.
Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO2 requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”
Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
Ventilation in life-threatening asthma
Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.
Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.
Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.
“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV1 – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.
On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.
“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.
Dr. Garner and Dr. Long disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In assessing and managing patients presenting with acute, life-threatening asthma, if the exacerbation does not resolve relatively quickly, clinicians need to start looking for other causes of the patient’s respiratory distress, a review of the literature suggests.
“I think one of the most important points of this review is that asthma is a self-limiting disease, and it’s important to understand that with appropriate treatment and immediate response to it, exacerbations will get better with time,” Orlando Garner, MD, Baylor College of Medicine, Houston, said in an interview.
“So I think one of the key points is, if these exacerbations do not resolve within 24-48 hours, clinicians need to start thinking: ‘This could be something else,’ and not get stuck in the diagnosis that this is an asthmatic patient who is having an exacerbation. If the distress doesn’t resolve within 48 hours, it’s time to look for other clues,” he stressed.
The study was published online in the journal CHEST®.
Appropriate triage
Appropriate triage is key in the management of acute asthma, Dr. Garner and colleagues pointed out. A simplified severity score for the evaluation of asthma in the ED can help in this regard. Depending on the presence or absence of a number of key signs and symptoms, patients can be readily categorized as having mild, moderate, or severe asthma. “Static assessments and dynamic assessments of acute asthma exacerbation in the ED can also help triage patients,” the authors added.
Static assessment involves assessing the severity at presentation, which in turn determines the aggressiveness of initial treatment. Objective static assessments include the measurement of peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1). A severe exacerbation is usually defined as a PEF or an FEV1 of less than 50%-60% of predicted normal values, the authors noted.
Dynamic assessment is more helpful than static assessment because it gauges response to treatment. “A lack of improvement in expiratory flow rates after initial bronchodilator therapy with continuous or worsening symptoms suggests need for hospitalization,” Dr. Garner and colleagues observed. The main treatment goals for patients with acute asthma are reversal of bronchospasm and correction of hypoxemia.
These are achieved at least initially with conventional agents, such as repeated doses of inhaled short-acting beta2-agonists, inhaled short-acting anticholinergics, systemic corticosteroids, and occasionally intravenous magnesium sulfate. If there is concomitant hypoxemia, oxygen therapy should be initiated as well. Patients who have evidence of hypercapnic respiratory failure or diaphragmatic fatigue need to be admitted to the intensive care unit, the authors indicated.
For these patients, clinicians need to remember that there are therapies other than inhalers, such as epinephrine and systemic terbutaline. During a life-threatening asthma episode, airflow in the medium and small airways often becomes turbulent, increasing the work of breathing, the researchers pointed out.
Heliox, a combination of helium and oxygen, reduces turbulent flow, they noted, although FiO2 requirements need to be less than 30% in order for it to work. “Heliox can be used in patients with severe bronchospasm who do not respond to the conventional therapies,” the authors noted, “[but] therapy should be abandoned if there is no clinical improvement after 15 minutes of use.”
Although none of the biologics such as dupilumab (Dupixent) has yet been approved for the treatment of acute exacerbations, Dr. Garner predicts they will become the “future of medicine” for patients with severe asthma as well.
Ventilation in life-threatening asthma
Rapid sequence intubation is generally recommended for patients who require mechanical ventilation, but as an alternative, “we are advocating a slower approach, where we get patients to slow down their breathing and relax them with something like ketamine infusions and wait before we given them a paralytic to see if the work of breathing improves,” Dr. Garner said. Bag-mask ventilation should be avoided because it can worsen dynamic hyperinflation or cause barotrauma.
Salvage therapies such as the use of bronchoscopy with N-acetylcysteine instilled directly into the airway is another option in cases in which mucus plugging is considered to be the main driver of airflow limitation.
Asked to comment, Brit Long, MD, an emergency medicine physician at the Brooke Army Medical Center in San Antonio, Tex., felt the review was extremely useful and well done.
“We see these patients very frequently, and being able to assess them right away and get an accurate picture of what’s going on is very important,” he said in an interview. The one thing that is often more difficult, at least in the ED, is obtaining a PEF or the FEV1 – “both very helpful if the patient can do them, but if the patient is critically ill, it’s more likely you will not be able to get those assessments, and if patients are speaking in one-word sentences and are working really hard to breathe, that’s a severe exacerbation, and they need immediate intervention.” Dr. Long also liked all the essential treatments the authors recommended that patients be given immediately, although he noted that Heliox is not going to be available in most EDs.
On the other hand, he agreed with the authors’ recommendation to take a slower approach to mechanical ventilation, if it is needed at all. “I try my best to absolutely avoid intubating these patients – you are not fixing the issue with mechanical ventilation, you are just creating further problems.
“And while I see the entire spectrum of asthma patients from very mild to severe patients, these authors did a good job in explaining what the goals of treatment are and what to do with the severe ones,” he said.
Dr. Garner and Dr. Long disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CHEST
Babies of pregnant women who get RSV vaccine likely to be prescribed fewer antimicrobials
Babies born to moms who were vaccinated against respiratory syncytial virus (RSV) while pregnant appear to need fewer antimicrobial prescriptions than babies of unvaccinated moms, according to authors of a recent study.
To fight antimicrobial resistance, we need to use fewer antimicrobial drugs, the authors write in Proceedings of the National Academy of Sciences.
“In this study, an RSV vaccine was administered to pregnant women to prevent infection in their infants by the transfer of protective antibody to the infant,” Kathryn M. Edwards, MD, a professor of pediatrics and the scientific director of the Vanderbilt vaccine research program at Vanderbilt University in Nashville, Tenn., told this news organization. Dr. Edwards was not involved in the study.
“The authors investigated the impact of the vaccine on the use of antibiotics in infants during the first 90 days of life,” Dr. Edwards added in an email. “They found that the use of antibiotics was less in infants born to mothers who received the RSV vaccine than in infants born to mothers who received placebo. … They suggest that reducing RSV infection in infants will reduce respiratory infections that trigger antibiotic use.”
Senior author Ramanan Laxminarayan, PhD, MPH, director and senior fellow at the Center for Disease Dynamics, Economics & Policy in Washington and his colleagues conducted a secondary analysis of a double-blind, randomized controlled trial at 87 sites in 11 countries on several continents.
In the original study, which was conducted between December 2015 and May 2018, 3,005 maternal participants and 2,978 infant participants received the experimental RSV F vaccine, and 1,573 maternal participants and 1,546 infants received a placebo shot. Baseline characteristics of mothers and infants were well balanced, according to the authors.
In the current study, infants born to mothers who received the RSV vaccine were found to be 12.9% (95% confidence interval, 1.3%-23.1%) less likely to be prescribed antimicrobials during their first 3 months of life, compared with infants whose mothers received placebo. Vaccine efficacy against antimicrobial prescriptions for acute lower respiratory tract infections was 16.9% (95% CI, 1.4%-29.4%).
During the first 3 months of life, for every 100 infants born, maternal vaccination prevented 3.6 courses of antimicrobials in high-income countries (20.2% of all antimicrobial prescribing), and 5.1 courses in low- and middle-income countries (10.9% of all antimicrobial prescribing).
In addition to finding that lower respiratory tract infections accounted for 69%-73% of all antimicrobial prescribing prevented by maternal vaccination, the researchers found marked vaccine efficacy (71.3% [95% CI, 28.1%-88.6%]) against acute otitis media–associated antimicrobial prescription in infants in high-income countries.
RSV vaccine is ‘one of our best investments’
RSV, the authors explain, is a major cause of upper and lower respiratory tract infections that develop as a single agent or along with bacterial pathogens.
“With decreases in bacterial pneumonia following the introduction of the pneumococcal conjugate vaccine, a vaccine against RSV represents one of our best investments to lower the burden of respiratory infections in children,” Dr. Laxminarayan said in a press release.
“These findings are not unexpected because viral infections can trigger bacterial infections such as otitis, and reducing viral infections will reduce bacterial infections,” Dr. Edwards said. “Also, viral infections are often treated with antibiotics because the provider cannot rule out a bacterial infection.”
She acknowledged the value of investigating multiple outcomes but added that “the study was underpowered to assess the full impact of the antibiotics.”
“If a more effective RSV vaccine can be designed, the impact on reducing antibiotic use will likely be even greater,” Dr. Edwards advised. “Also, the vaccine was not highly effective in preventing RSV pneumonia. If it had been more effective, the antibiotic impact would likely have been greater.”
The authors acknowledged the study’s limitations. “Results of this post hoc secondary analysis should be viewed as hypothesis generating, as the trial was not powered for determination of effects against antimicrobial prescribing, and our analyses were not adjusted for multiplicity,” they write, and they joined Dr. Edwards in recommending further related research.
First author Joseph A. Lewnard, PhD, declares financial support from Pfizer unrelated to this research, three authors are employees of Novavax, and Dr. Laxminarayan has disclosed no relevant financial relationships. Dr. Edwards reports funding from the National Institutes of Health and the Centers for Disease Control and Prevention; consultancy to BioNEt and IBM; membership on data safety and monitoring boards for Pfizer, Sanofi, GSK, Merck, X-4 Pharma, Roche, and Seqirus. The Bill & Melinda Gates Foundation supported the study.
A version of this article first appeared on Medscape.com.
Babies born to moms who were vaccinated against respiratory syncytial virus (RSV) while pregnant appear to need fewer antimicrobial prescriptions than babies of unvaccinated moms, according to authors of a recent study.
To fight antimicrobial resistance, we need to use fewer antimicrobial drugs, the authors write in Proceedings of the National Academy of Sciences.
“In this study, an RSV vaccine was administered to pregnant women to prevent infection in their infants by the transfer of protective antibody to the infant,” Kathryn M. Edwards, MD, a professor of pediatrics and the scientific director of the Vanderbilt vaccine research program at Vanderbilt University in Nashville, Tenn., told this news organization. Dr. Edwards was not involved in the study.
“The authors investigated the impact of the vaccine on the use of antibiotics in infants during the first 90 days of life,” Dr. Edwards added in an email. “They found that the use of antibiotics was less in infants born to mothers who received the RSV vaccine than in infants born to mothers who received placebo. … They suggest that reducing RSV infection in infants will reduce respiratory infections that trigger antibiotic use.”
Senior author Ramanan Laxminarayan, PhD, MPH, director and senior fellow at the Center for Disease Dynamics, Economics & Policy in Washington and his colleagues conducted a secondary analysis of a double-blind, randomized controlled trial at 87 sites in 11 countries on several continents.
In the original study, which was conducted between December 2015 and May 2018, 3,005 maternal participants and 2,978 infant participants received the experimental RSV F vaccine, and 1,573 maternal participants and 1,546 infants received a placebo shot. Baseline characteristics of mothers and infants were well balanced, according to the authors.
In the current study, infants born to mothers who received the RSV vaccine were found to be 12.9% (95% confidence interval, 1.3%-23.1%) less likely to be prescribed antimicrobials during their first 3 months of life, compared with infants whose mothers received placebo. Vaccine efficacy against antimicrobial prescriptions for acute lower respiratory tract infections was 16.9% (95% CI, 1.4%-29.4%).
During the first 3 months of life, for every 100 infants born, maternal vaccination prevented 3.6 courses of antimicrobials in high-income countries (20.2% of all antimicrobial prescribing), and 5.1 courses in low- and middle-income countries (10.9% of all antimicrobial prescribing).
In addition to finding that lower respiratory tract infections accounted for 69%-73% of all antimicrobial prescribing prevented by maternal vaccination, the researchers found marked vaccine efficacy (71.3% [95% CI, 28.1%-88.6%]) against acute otitis media–associated antimicrobial prescription in infants in high-income countries.
RSV vaccine is ‘one of our best investments’
RSV, the authors explain, is a major cause of upper and lower respiratory tract infections that develop as a single agent or along with bacterial pathogens.
“With decreases in bacterial pneumonia following the introduction of the pneumococcal conjugate vaccine, a vaccine against RSV represents one of our best investments to lower the burden of respiratory infections in children,” Dr. Laxminarayan said in a press release.
“These findings are not unexpected because viral infections can trigger bacterial infections such as otitis, and reducing viral infections will reduce bacterial infections,” Dr. Edwards said. “Also, viral infections are often treated with antibiotics because the provider cannot rule out a bacterial infection.”
She acknowledged the value of investigating multiple outcomes but added that “the study was underpowered to assess the full impact of the antibiotics.”
“If a more effective RSV vaccine can be designed, the impact on reducing antibiotic use will likely be even greater,” Dr. Edwards advised. “Also, the vaccine was not highly effective in preventing RSV pneumonia. If it had been more effective, the antibiotic impact would likely have been greater.”
The authors acknowledged the study’s limitations. “Results of this post hoc secondary analysis should be viewed as hypothesis generating, as the trial was not powered for determination of effects against antimicrobial prescribing, and our analyses were not adjusted for multiplicity,” they write, and they joined Dr. Edwards in recommending further related research.
First author Joseph A. Lewnard, PhD, declares financial support from Pfizer unrelated to this research, three authors are employees of Novavax, and Dr. Laxminarayan has disclosed no relevant financial relationships. Dr. Edwards reports funding from the National Institutes of Health and the Centers for Disease Control and Prevention; consultancy to BioNEt and IBM; membership on data safety and monitoring boards for Pfizer, Sanofi, GSK, Merck, X-4 Pharma, Roche, and Seqirus. The Bill & Melinda Gates Foundation supported the study.
A version of this article first appeared on Medscape.com.
Babies born to moms who were vaccinated against respiratory syncytial virus (RSV) while pregnant appear to need fewer antimicrobial prescriptions than babies of unvaccinated moms, according to authors of a recent study.
To fight antimicrobial resistance, we need to use fewer antimicrobial drugs, the authors write in Proceedings of the National Academy of Sciences.
“In this study, an RSV vaccine was administered to pregnant women to prevent infection in their infants by the transfer of protective antibody to the infant,” Kathryn M. Edwards, MD, a professor of pediatrics and the scientific director of the Vanderbilt vaccine research program at Vanderbilt University in Nashville, Tenn., told this news organization. Dr. Edwards was not involved in the study.
“The authors investigated the impact of the vaccine on the use of antibiotics in infants during the first 90 days of life,” Dr. Edwards added in an email. “They found that the use of antibiotics was less in infants born to mothers who received the RSV vaccine than in infants born to mothers who received placebo. … They suggest that reducing RSV infection in infants will reduce respiratory infections that trigger antibiotic use.”
Senior author Ramanan Laxminarayan, PhD, MPH, director and senior fellow at the Center for Disease Dynamics, Economics & Policy in Washington and his colleagues conducted a secondary analysis of a double-blind, randomized controlled trial at 87 sites in 11 countries on several continents.
In the original study, which was conducted between December 2015 and May 2018, 3,005 maternal participants and 2,978 infant participants received the experimental RSV F vaccine, and 1,573 maternal participants and 1,546 infants received a placebo shot. Baseline characteristics of mothers and infants were well balanced, according to the authors.
In the current study, infants born to mothers who received the RSV vaccine were found to be 12.9% (95% confidence interval, 1.3%-23.1%) less likely to be prescribed antimicrobials during their first 3 months of life, compared with infants whose mothers received placebo. Vaccine efficacy against antimicrobial prescriptions for acute lower respiratory tract infections was 16.9% (95% CI, 1.4%-29.4%).
During the first 3 months of life, for every 100 infants born, maternal vaccination prevented 3.6 courses of antimicrobials in high-income countries (20.2% of all antimicrobial prescribing), and 5.1 courses in low- and middle-income countries (10.9% of all antimicrobial prescribing).
In addition to finding that lower respiratory tract infections accounted for 69%-73% of all antimicrobial prescribing prevented by maternal vaccination, the researchers found marked vaccine efficacy (71.3% [95% CI, 28.1%-88.6%]) against acute otitis media–associated antimicrobial prescription in infants in high-income countries.
RSV vaccine is ‘one of our best investments’
RSV, the authors explain, is a major cause of upper and lower respiratory tract infections that develop as a single agent or along with bacterial pathogens.
“With decreases in bacterial pneumonia following the introduction of the pneumococcal conjugate vaccine, a vaccine against RSV represents one of our best investments to lower the burden of respiratory infections in children,” Dr. Laxminarayan said in a press release.
“These findings are not unexpected because viral infections can trigger bacterial infections such as otitis, and reducing viral infections will reduce bacterial infections,” Dr. Edwards said. “Also, viral infections are often treated with antibiotics because the provider cannot rule out a bacterial infection.”
She acknowledged the value of investigating multiple outcomes but added that “the study was underpowered to assess the full impact of the antibiotics.”
“If a more effective RSV vaccine can be designed, the impact on reducing antibiotic use will likely be even greater,” Dr. Edwards advised. “Also, the vaccine was not highly effective in preventing RSV pneumonia. If it had been more effective, the antibiotic impact would likely have been greater.”
The authors acknowledged the study’s limitations. “Results of this post hoc secondary analysis should be viewed as hypothesis generating, as the trial was not powered for determination of effects against antimicrobial prescribing, and our analyses were not adjusted for multiplicity,” they write, and they joined Dr. Edwards in recommending further related research.
First author Joseph A. Lewnard, PhD, declares financial support from Pfizer unrelated to this research, three authors are employees of Novavax, and Dr. Laxminarayan has disclosed no relevant financial relationships. Dr. Edwards reports funding from the National Institutes of Health and the Centers for Disease Control and Prevention; consultancy to BioNEt and IBM; membership on data safety and monitoring boards for Pfizer, Sanofi, GSK, Merck, X-4 Pharma, Roche, and Seqirus. The Bill & Melinda Gates Foundation supported the study.
A version of this article first appeared on Medscape.com.
FROM PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
Infectious disease pop quiz: Clinical challenge #19 for the ObGyn
Should a postpartum patient with chronic hepatitis C infection be discouraged from breastfeeding her infant?
Continue to the answer...
Hepatitis C is not a contraindication to breastfeeding. Although the virus has been identified in breast milk, the risk of transmission to the infant is exceedingly low.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Should a postpartum patient with chronic hepatitis C infection be discouraged from breastfeeding her infant?
Continue to the answer...
Hepatitis C is not a contraindication to breastfeeding. Although the virus has been identified in breast milk, the risk of transmission to the infant is exceedingly low.
Should a postpartum patient with chronic hepatitis C infection be discouraged from breastfeeding her infant?
Continue to the answer...
Hepatitis C is not a contraindication to breastfeeding. Although the virus has been identified in breast milk, the risk of transmission to the infant is exceedingly low.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Doctors have failed them, say those with transgender regret
In a unique Zoom conference,
The forum was convened on what was dubbed #DetransitionAwarenessDay by Genspect, a parent-based organization that seeks to put the brakes on medical transitions for children and adolescents. The group has doubts about the gender-affirming care model supported by the World Professional Association for Transgender Health, the American Medical Association, the American Academy of Pediatrics, and other medical groups.
“Affirmative” medical care is defined as treatment with puberty blockers and cross-sex hormones for those with gender dysphoria to transition to the opposite sex and is often followed by gender reassignment surgery. However, there is growing concern among many doctors and other health care professionals as to whether this is, in fact, the best way to proceed for those under aged 18, in particular, with several countries pulling back on medical treatment and instead emphasizing psychotherapy first.
The purpose of the second annual Genspect meeting was to shed light on the experiences of individuals who have detransitioned – those that identified as transgender and transitioned, but then decided to end their medical transition. People logged on from all over the United States, Canada, New Zealand, Australia, the United Kingdom, Germany, Spain, Chile, and Brazil, among other countries.
“This is a minority within a minority,” said Genspect advisor Stella O’Malley, adding that the first meeting in 2021 was held because “too many people were dismissing the stories of the detransitioners.” Ms. O’Malley is a psychotherapist, a clinical advisor to the Society for Evidence-Based Gender Medicine, and a founding member of the International Association of Therapists for Desisters and Detransitioners.
“It’s become blindingly obvious over the last year that ... ‘detrans’ is a huge part of the trans phenomenon,” said Ms. O’Malley, adding that detransitioners have been “undermined and dismissed.”
Laura Edwards-Leeper, PhD (@DrLauraEL), a prominent gender therapist who has recently expressed concern regarding adequate gatekeeping when treating youth with gender dysphoria, agreed.
She tweeted: “You simply can’t call yourself a legit gender provider if you don’t believe that detransitioners exist. As part of the informed consent process for transitioning, it is unethical to not discuss this possibility with young people.” Dr. Edwards-Leeper is professor emeritus at Pacific University in Hillsboro, Ore.
Speakers in the forum largely offered experiences, not data. They pointed out that there has been little to no study of detransition, but all testified that it was less rare than it has been portrayed by the transgender community.
Struggles with going back
“There are so many reasons why people detransition,” said Sinead Watson, aged 30, a Genspect advisor who transitioned from female to male, starting in 2015, and who decided to detransition in 2019. Citing a study by Lisa Littman, MD, MPH, published in 2021, Ms. Watson said the most common reasons for detransitioning were realizing that gender dysphoria was caused by other issues; internal homophobia; and the unbearable nature of transphobia.
Ms. Watson said the hardest part of detransitioning was admitting to herself that her transition had been a mistake. “It’s embarrassing and you feel ashamed and guilty,” she said, adding that it may mean losing friends who now regard you as a “bigot, while you’re also dealing with transition regret.”
“It’s a living hell, especially when none of your therapists or counselors will listen to you,” she said. “Detransitioning isn’t fun.”
Carol (@sourpatches2077) said she knew for a year that her transition had been a mistake.
“The biggest part was I couldn’t tell my family,” said Carol, who identifies as a lesbian. “I put them through so much. It seems ridiculous to go: ‘Oops, I made this huge [expletive] mistake,’ ” she said, describing the moment she did tell them as “devastating.”
Grace (@hormonehangover) said she remembers finally hitting a moment of “undeniability” some years after transitioning. “I accept it, I’ve ruined my life, this is wrong,” she remembers thinking. “It was devastating, but I couldn’t deny it anymore.”
Don’t trust therapists
People experiencing feelings of unease “need a therapist who will listen to them,” said Ms. Watson. When she first detransitioned, her therapists treated her badly. “They just didn’t want to speak about detransition,” she said, adding that “it was like a kick in the stomach.”
Ms. Watson said she’d like to see more training about detransition, but also on “preventative techniques,” adding that many people transition who should not. “I don’t want more detransitioners – I want less.
“In order for that to happen, we need to treat people with gender dysphoria properly,” said Ms. Watson, adding that the affirmative model is “disgusting, and that’s what needs to change.”
“I would tell somebody to not go to a therapist,” said Carol. Identifying as a butch lesbian, she felt like her therapists had pushed her into transitioning to male. “The No. 1 thing not understood by the mental health professionals is that the vast majority of homosexuals were gender-nonconforming children.” She added that this is especially true of butch lesbians.
Therapists – and doctors – also need to acknowledge both the trauma of transition and detransition, she said.
Kaiser, where she had transitioned, offered her breast reconstruction. Carol said it felt demeaning. “Like you’re Mr. Potatohead: ‘Here, we can just ... put on some new parts and you’re good to go.’ ”
“Doctors are concretizing transient obsessions,” said Helena Kerschner (@lacroicsz), quoting a chatroom user.
Ms. Kerschner gave a presentation on “fandom”: becoming obsessed with a movie, book, TV show, musician, or celebrity, spending every waking hour chatting online or writing fan fiction, or attempting to interact with the celebrity online. It’s a fantasy-dominated world and “the vast majority” of participants are teenage girls who are “identifying as trans,” in part, because they are fed a community-reinforced message that it’s better to be a boy.
Therapists and physicians who help them transition “are harming them for life based on something they would have grown out of or overcome without the permanent damage,” Ms. Kerschner added.
Doctors ‘gaslighting’ people into believing that transition is the answer
A pervasive theme during the webinar was that many people are being misdiagnosed with gender dysphoria, which may not be resolved by medical transition.
Allie, a 22-year-old who stopped taking testosterone after 1½ years, said she initially started the transition to male when she gave up trying to figure out why she could not identify with, or befriend, women, and after a childhood and adolescence spent mostly in the company of boys and being more interested in traditionally male activities.
She endured sexual abuse as a teenager and her parents divorced while she was in high school. Allie also had multiple suicide attempts and many incidents of self-harm. When she decided to transition, at age 18, she went to a private clinic and received cross-sex hormones within a few months of her first and only 30-minute consultation. “There was no explorative therapy,” she said, adding that she was never given a formal diagnosis of gender dysphoria.
For the first year, she said she was “over the freaking moon” because she felt like it was the answer. But things started to unravel while she attended university, and she attempted suicide attempt at age 20. A social worker at the school identified her symptoms – which had been the same since childhood – as autism. She then decided to cease her transition.
Another detransitioner, Laura Becker, said it took 5 years after her transition to recognize that she had undiagnosed PTSD from emotional and psychiatric abuse. Despite a history of substance abuse, self-harm, suicidal ideation, and other mental health issues, she was given testosterone and had a double mastectomy at age 20. She became fixated on gay men, which devolved into a methamphetamine- and crack-fueled relationship with a man she met on the gay dating platform Grindr.
“No one around me knew any better or knew how to help, including the medical professionals who performed the mastectomy and who casually signed off and administered my medical transition,” she said.
Once she was aware of her PTSD she started to detransition, which itself was traumatic, said Laura.
Limpida, aged 24, said he felt pushed into transitioning after seeking help at a Planned Parenthood clinic. He identified as trans at age 15 and spent years attempting to be a woman socially, but every step made him feel more miserable, he said. When he went to the clinic at age 21 to get estrogen, he said he felt like the staff was dismissive of his mental health concerns – including that he was suicidal, had substance abuse, and was severely depressed. He was told he was the “perfect candidate” for transitioning.
A year later, he said he felt worse. The nurse suggested he seek out surgery. After Limpida researched what was involved, he decided to detransition. He has since received an autism diagnosis.
Robin, also aged 24, said the idea of surgery had helped push him into detransitioning, which began in 2020 after 4 years of estrogen. He said he had always been gender nonconforming and knew he was gay at an early age. He believes that gender-nonconforming people are “gaslighted” into thinking that transitioning is the answer.
Lack of evidence-based, informed consent
Michelle Alleva, who stopped identifying as transgender in 2020 but had ceased testosterone 4 years earlier because of side effects, cited what she called a lack of evidence base for the effectiveness and safety of medical transitions.
“You need to have a really, really good evidence base in place if you’re going straight to an invasive treatment that is going to cause permanent changes to your body,” she said.
Access to medical transition used to involve more “gatekeeping” through mental health evaluations and other interventions, she said, but there has been a shift from treating what was considered a psychiatric issue to essentially affirming an identity.
“This shift was activist driven, not evidence based,” she emphasized.
Most studies showing satisfaction with transition only involve a few years of follow-up, she said. She added that the longest follow-up study of transition, published in 2011 and spanning 30 years, showed that the suicide rate 10-15 years post surgery was 20 times higher than the general population.
Studies of regret were primarily conducted before the rapid increase in the number of trans-identifying individuals, she said, which makes it hard to draw conclusions about pediatric transition. Getting estimates on this population is difficult because so many who detransition do not tell their clinicians, and many studies have short follow-up times or a high loss to follow-up.
Ms. Alleva also took issue with the notion that physicians were offering true informed consent, noting that it’s not possible to know if someone is psychologically sound if they haven’t had a thorough mental health evaluation and that there are so many unknowns with medical transition, including that many of the therapies are not approved for the uses being employed.
With regret on the rise, “we need professionals that are prepared for detransitioners,” said Ms. Alleva. “Some of us have lost trust in health care professionals as a result of our experience.”
“It’s a huge feeling of institutional betrayal,” said Grace.
A version of this article first appeared on Medscape.com.
In a unique Zoom conference,
The forum was convened on what was dubbed #DetransitionAwarenessDay by Genspect, a parent-based organization that seeks to put the brakes on medical transitions for children and adolescents. The group has doubts about the gender-affirming care model supported by the World Professional Association for Transgender Health, the American Medical Association, the American Academy of Pediatrics, and other medical groups.
“Affirmative” medical care is defined as treatment with puberty blockers and cross-sex hormones for those with gender dysphoria to transition to the opposite sex and is often followed by gender reassignment surgery. However, there is growing concern among many doctors and other health care professionals as to whether this is, in fact, the best way to proceed for those under aged 18, in particular, with several countries pulling back on medical treatment and instead emphasizing psychotherapy first.
The purpose of the second annual Genspect meeting was to shed light on the experiences of individuals who have detransitioned – those that identified as transgender and transitioned, but then decided to end their medical transition. People logged on from all over the United States, Canada, New Zealand, Australia, the United Kingdom, Germany, Spain, Chile, and Brazil, among other countries.
“This is a minority within a minority,” said Genspect advisor Stella O’Malley, adding that the first meeting in 2021 was held because “too many people were dismissing the stories of the detransitioners.” Ms. O’Malley is a psychotherapist, a clinical advisor to the Society for Evidence-Based Gender Medicine, and a founding member of the International Association of Therapists for Desisters and Detransitioners.
“It’s become blindingly obvious over the last year that ... ‘detrans’ is a huge part of the trans phenomenon,” said Ms. O’Malley, adding that detransitioners have been “undermined and dismissed.”
Laura Edwards-Leeper, PhD (@DrLauraEL), a prominent gender therapist who has recently expressed concern regarding adequate gatekeeping when treating youth with gender dysphoria, agreed.
She tweeted: “You simply can’t call yourself a legit gender provider if you don’t believe that detransitioners exist. As part of the informed consent process for transitioning, it is unethical to not discuss this possibility with young people.” Dr. Edwards-Leeper is professor emeritus at Pacific University in Hillsboro, Ore.
Speakers in the forum largely offered experiences, not data. They pointed out that there has been little to no study of detransition, but all testified that it was less rare than it has been portrayed by the transgender community.
Struggles with going back
“There are so many reasons why people detransition,” said Sinead Watson, aged 30, a Genspect advisor who transitioned from female to male, starting in 2015, and who decided to detransition in 2019. Citing a study by Lisa Littman, MD, MPH, published in 2021, Ms. Watson said the most common reasons for detransitioning were realizing that gender dysphoria was caused by other issues; internal homophobia; and the unbearable nature of transphobia.
Ms. Watson said the hardest part of detransitioning was admitting to herself that her transition had been a mistake. “It’s embarrassing and you feel ashamed and guilty,” she said, adding that it may mean losing friends who now regard you as a “bigot, while you’re also dealing with transition regret.”
“It’s a living hell, especially when none of your therapists or counselors will listen to you,” she said. “Detransitioning isn’t fun.”
Carol (@sourpatches2077) said she knew for a year that her transition had been a mistake.
“The biggest part was I couldn’t tell my family,” said Carol, who identifies as a lesbian. “I put them through so much. It seems ridiculous to go: ‘Oops, I made this huge [expletive] mistake,’ ” she said, describing the moment she did tell them as “devastating.”
Grace (@hormonehangover) said she remembers finally hitting a moment of “undeniability” some years after transitioning. “I accept it, I’ve ruined my life, this is wrong,” she remembers thinking. “It was devastating, but I couldn’t deny it anymore.”
Don’t trust therapists
People experiencing feelings of unease “need a therapist who will listen to them,” said Ms. Watson. When she first detransitioned, her therapists treated her badly. “They just didn’t want to speak about detransition,” she said, adding that “it was like a kick in the stomach.”
Ms. Watson said she’d like to see more training about detransition, but also on “preventative techniques,” adding that many people transition who should not. “I don’t want more detransitioners – I want less.
“In order for that to happen, we need to treat people with gender dysphoria properly,” said Ms. Watson, adding that the affirmative model is “disgusting, and that’s what needs to change.”
“I would tell somebody to not go to a therapist,” said Carol. Identifying as a butch lesbian, she felt like her therapists had pushed her into transitioning to male. “The No. 1 thing not understood by the mental health professionals is that the vast majority of homosexuals were gender-nonconforming children.” She added that this is especially true of butch lesbians.
Therapists – and doctors – also need to acknowledge both the trauma of transition and detransition, she said.
Kaiser, where she had transitioned, offered her breast reconstruction. Carol said it felt demeaning. “Like you’re Mr. Potatohead: ‘Here, we can just ... put on some new parts and you’re good to go.’ ”
“Doctors are concretizing transient obsessions,” said Helena Kerschner (@lacroicsz), quoting a chatroom user.
Ms. Kerschner gave a presentation on “fandom”: becoming obsessed with a movie, book, TV show, musician, or celebrity, spending every waking hour chatting online or writing fan fiction, or attempting to interact with the celebrity online. It’s a fantasy-dominated world and “the vast majority” of participants are teenage girls who are “identifying as trans,” in part, because they are fed a community-reinforced message that it’s better to be a boy.
Therapists and physicians who help them transition “are harming them for life based on something they would have grown out of or overcome without the permanent damage,” Ms. Kerschner added.
Doctors ‘gaslighting’ people into believing that transition is the answer
A pervasive theme during the webinar was that many people are being misdiagnosed with gender dysphoria, which may not be resolved by medical transition.
Allie, a 22-year-old who stopped taking testosterone after 1½ years, said she initially started the transition to male when she gave up trying to figure out why she could not identify with, or befriend, women, and after a childhood and adolescence spent mostly in the company of boys and being more interested in traditionally male activities.
She endured sexual abuse as a teenager and her parents divorced while she was in high school. Allie also had multiple suicide attempts and many incidents of self-harm. When she decided to transition, at age 18, she went to a private clinic and received cross-sex hormones within a few months of her first and only 30-minute consultation. “There was no explorative therapy,” she said, adding that she was never given a formal diagnosis of gender dysphoria.
For the first year, she said she was “over the freaking moon” because she felt like it was the answer. But things started to unravel while she attended university, and she attempted suicide attempt at age 20. A social worker at the school identified her symptoms – which had been the same since childhood – as autism. She then decided to cease her transition.
Another detransitioner, Laura Becker, said it took 5 years after her transition to recognize that she had undiagnosed PTSD from emotional and psychiatric abuse. Despite a history of substance abuse, self-harm, suicidal ideation, and other mental health issues, she was given testosterone and had a double mastectomy at age 20. She became fixated on gay men, which devolved into a methamphetamine- and crack-fueled relationship with a man she met on the gay dating platform Grindr.
“No one around me knew any better or knew how to help, including the medical professionals who performed the mastectomy and who casually signed off and administered my medical transition,” she said.
Once she was aware of her PTSD she started to detransition, which itself was traumatic, said Laura.
Limpida, aged 24, said he felt pushed into transitioning after seeking help at a Planned Parenthood clinic. He identified as trans at age 15 and spent years attempting to be a woman socially, but every step made him feel more miserable, he said. When he went to the clinic at age 21 to get estrogen, he said he felt like the staff was dismissive of his mental health concerns – including that he was suicidal, had substance abuse, and was severely depressed. He was told he was the “perfect candidate” for transitioning.
A year later, he said he felt worse. The nurse suggested he seek out surgery. After Limpida researched what was involved, he decided to detransition. He has since received an autism diagnosis.
Robin, also aged 24, said the idea of surgery had helped push him into detransitioning, which began in 2020 after 4 years of estrogen. He said he had always been gender nonconforming and knew he was gay at an early age. He believes that gender-nonconforming people are “gaslighted” into thinking that transitioning is the answer.
Lack of evidence-based, informed consent
Michelle Alleva, who stopped identifying as transgender in 2020 but had ceased testosterone 4 years earlier because of side effects, cited what she called a lack of evidence base for the effectiveness and safety of medical transitions.
“You need to have a really, really good evidence base in place if you’re going straight to an invasive treatment that is going to cause permanent changes to your body,” she said.
Access to medical transition used to involve more “gatekeeping” through mental health evaluations and other interventions, she said, but there has been a shift from treating what was considered a psychiatric issue to essentially affirming an identity.
“This shift was activist driven, not evidence based,” she emphasized.
Most studies showing satisfaction with transition only involve a few years of follow-up, she said. She added that the longest follow-up study of transition, published in 2011 and spanning 30 years, showed that the suicide rate 10-15 years post surgery was 20 times higher than the general population.
Studies of regret were primarily conducted before the rapid increase in the number of trans-identifying individuals, she said, which makes it hard to draw conclusions about pediatric transition. Getting estimates on this population is difficult because so many who detransition do not tell their clinicians, and many studies have short follow-up times or a high loss to follow-up.
Ms. Alleva also took issue with the notion that physicians were offering true informed consent, noting that it’s not possible to know if someone is psychologically sound if they haven’t had a thorough mental health evaluation and that there are so many unknowns with medical transition, including that many of the therapies are not approved for the uses being employed.
With regret on the rise, “we need professionals that are prepared for detransitioners,” said Ms. Alleva. “Some of us have lost trust in health care professionals as a result of our experience.”
“It’s a huge feeling of institutional betrayal,” said Grace.
A version of this article first appeared on Medscape.com.
In a unique Zoom conference,
The forum was convened on what was dubbed #DetransitionAwarenessDay by Genspect, a parent-based organization that seeks to put the brakes on medical transitions for children and adolescents. The group has doubts about the gender-affirming care model supported by the World Professional Association for Transgender Health, the American Medical Association, the American Academy of Pediatrics, and other medical groups.
“Affirmative” medical care is defined as treatment with puberty blockers and cross-sex hormones for those with gender dysphoria to transition to the opposite sex and is often followed by gender reassignment surgery. However, there is growing concern among many doctors and other health care professionals as to whether this is, in fact, the best way to proceed for those under aged 18, in particular, with several countries pulling back on medical treatment and instead emphasizing psychotherapy first.
The purpose of the second annual Genspect meeting was to shed light on the experiences of individuals who have detransitioned – those that identified as transgender and transitioned, but then decided to end their medical transition. People logged on from all over the United States, Canada, New Zealand, Australia, the United Kingdom, Germany, Spain, Chile, and Brazil, among other countries.
“This is a minority within a minority,” said Genspect advisor Stella O’Malley, adding that the first meeting in 2021 was held because “too many people were dismissing the stories of the detransitioners.” Ms. O’Malley is a psychotherapist, a clinical advisor to the Society for Evidence-Based Gender Medicine, and a founding member of the International Association of Therapists for Desisters and Detransitioners.
“It’s become blindingly obvious over the last year that ... ‘detrans’ is a huge part of the trans phenomenon,” said Ms. O’Malley, adding that detransitioners have been “undermined and dismissed.”
Laura Edwards-Leeper, PhD (@DrLauraEL), a prominent gender therapist who has recently expressed concern regarding adequate gatekeeping when treating youth with gender dysphoria, agreed.
She tweeted: “You simply can’t call yourself a legit gender provider if you don’t believe that detransitioners exist. As part of the informed consent process for transitioning, it is unethical to not discuss this possibility with young people.” Dr. Edwards-Leeper is professor emeritus at Pacific University in Hillsboro, Ore.
Speakers in the forum largely offered experiences, not data. They pointed out that there has been little to no study of detransition, but all testified that it was less rare than it has been portrayed by the transgender community.
Struggles with going back
“There are so many reasons why people detransition,” said Sinead Watson, aged 30, a Genspect advisor who transitioned from female to male, starting in 2015, and who decided to detransition in 2019. Citing a study by Lisa Littman, MD, MPH, published in 2021, Ms. Watson said the most common reasons for detransitioning were realizing that gender dysphoria was caused by other issues; internal homophobia; and the unbearable nature of transphobia.
Ms. Watson said the hardest part of detransitioning was admitting to herself that her transition had been a mistake. “It’s embarrassing and you feel ashamed and guilty,” she said, adding that it may mean losing friends who now regard you as a “bigot, while you’re also dealing with transition regret.”
“It’s a living hell, especially when none of your therapists or counselors will listen to you,” she said. “Detransitioning isn’t fun.”
Carol (@sourpatches2077) said she knew for a year that her transition had been a mistake.
“The biggest part was I couldn’t tell my family,” said Carol, who identifies as a lesbian. “I put them through so much. It seems ridiculous to go: ‘Oops, I made this huge [expletive] mistake,’ ” she said, describing the moment she did tell them as “devastating.”
Grace (@hormonehangover) said she remembers finally hitting a moment of “undeniability” some years after transitioning. “I accept it, I’ve ruined my life, this is wrong,” she remembers thinking. “It was devastating, but I couldn’t deny it anymore.”
Don’t trust therapists
People experiencing feelings of unease “need a therapist who will listen to them,” said Ms. Watson. When she first detransitioned, her therapists treated her badly. “They just didn’t want to speak about detransition,” she said, adding that “it was like a kick in the stomach.”
Ms. Watson said she’d like to see more training about detransition, but also on “preventative techniques,” adding that many people transition who should not. “I don’t want more detransitioners – I want less.
“In order for that to happen, we need to treat people with gender dysphoria properly,” said Ms. Watson, adding that the affirmative model is “disgusting, and that’s what needs to change.”
“I would tell somebody to not go to a therapist,” said Carol. Identifying as a butch lesbian, she felt like her therapists had pushed her into transitioning to male. “The No. 1 thing not understood by the mental health professionals is that the vast majority of homosexuals were gender-nonconforming children.” She added that this is especially true of butch lesbians.
Therapists – and doctors – also need to acknowledge both the trauma of transition and detransition, she said.
Kaiser, where she had transitioned, offered her breast reconstruction. Carol said it felt demeaning. “Like you’re Mr. Potatohead: ‘Here, we can just ... put on some new parts and you’re good to go.’ ”
“Doctors are concretizing transient obsessions,” said Helena Kerschner (@lacroicsz), quoting a chatroom user.
Ms. Kerschner gave a presentation on “fandom”: becoming obsessed with a movie, book, TV show, musician, or celebrity, spending every waking hour chatting online or writing fan fiction, or attempting to interact with the celebrity online. It’s a fantasy-dominated world and “the vast majority” of participants are teenage girls who are “identifying as trans,” in part, because they are fed a community-reinforced message that it’s better to be a boy.
Therapists and physicians who help them transition “are harming them for life based on something they would have grown out of or overcome without the permanent damage,” Ms. Kerschner added.
Doctors ‘gaslighting’ people into believing that transition is the answer
A pervasive theme during the webinar was that many people are being misdiagnosed with gender dysphoria, which may not be resolved by medical transition.
Allie, a 22-year-old who stopped taking testosterone after 1½ years, said she initially started the transition to male when she gave up trying to figure out why she could not identify with, or befriend, women, and after a childhood and adolescence spent mostly in the company of boys and being more interested in traditionally male activities.
She endured sexual abuse as a teenager and her parents divorced while she was in high school. Allie also had multiple suicide attempts and many incidents of self-harm. When she decided to transition, at age 18, she went to a private clinic and received cross-sex hormones within a few months of her first and only 30-minute consultation. “There was no explorative therapy,” she said, adding that she was never given a formal diagnosis of gender dysphoria.
For the first year, she said she was “over the freaking moon” because she felt like it was the answer. But things started to unravel while she attended university, and she attempted suicide attempt at age 20. A social worker at the school identified her symptoms – which had been the same since childhood – as autism. She then decided to cease her transition.
Another detransitioner, Laura Becker, said it took 5 years after her transition to recognize that she had undiagnosed PTSD from emotional and psychiatric abuse. Despite a history of substance abuse, self-harm, suicidal ideation, and other mental health issues, she was given testosterone and had a double mastectomy at age 20. She became fixated on gay men, which devolved into a methamphetamine- and crack-fueled relationship with a man she met on the gay dating platform Grindr.
“No one around me knew any better or knew how to help, including the medical professionals who performed the mastectomy and who casually signed off and administered my medical transition,” she said.
Once she was aware of her PTSD she started to detransition, which itself was traumatic, said Laura.
Limpida, aged 24, said he felt pushed into transitioning after seeking help at a Planned Parenthood clinic. He identified as trans at age 15 and spent years attempting to be a woman socially, but every step made him feel more miserable, he said. When he went to the clinic at age 21 to get estrogen, he said he felt like the staff was dismissive of his mental health concerns – including that he was suicidal, had substance abuse, and was severely depressed. He was told he was the “perfect candidate” for transitioning.
A year later, he said he felt worse. The nurse suggested he seek out surgery. After Limpida researched what was involved, he decided to detransition. He has since received an autism diagnosis.
Robin, also aged 24, said the idea of surgery had helped push him into detransitioning, which began in 2020 after 4 years of estrogen. He said he had always been gender nonconforming and knew he was gay at an early age. He believes that gender-nonconforming people are “gaslighted” into thinking that transitioning is the answer.
Lack of evidence-based, informed consent
Michelle Alleva, who stopped identifying as transgender in 2020 but had ceased testosterone 4 years earlier because of side effects, cited what she called a lack of evidence base for the effectiveness and safety of medical transitions.
“You need to have a really, really good evidence base in place if you’re going straight to an invasive treatment that is going to cause permanent changes to your body,” she said.
Access to medical transition used to involve more “gatekeeping” through mental health evaluations and other interventions, she said, but there has been a shift from treating what was considered a psychiatric issue to essentially affirming an identity.
“This shift was activist driven, not evidence based,” she emphasized.
Most studies showing satisfaction with transition only involve a few years of follow-up, she said. She added that the longest follow-up study of transition, published in 2011 and spanning 30 years, showed that the suicide rate 10-15 years post surgery was 20 times higher than the general population.
Studies of regret were primarily conducted before the rapid increase in the number of trans-identifying individuals, she said, which makes it hard to draw conclusions about pediatric transition. Getting estimates on this population is difficult because so many who detransition do not tell their clinicians, and many studies have short follow-up times or a high loss to follow-up.
Ms. Alleva also took issue with the notion that physicians were offering true informed consent, noting that it’s not possible to know if someone is psychologically sound if they haven’t had a thorough mental health evaluation and that there are so many unknowns with medical transition, including that many of the therapies are not approved for the uses being employed.
With regret on the rise, “we need professionals that are prepared for detransitioners,” said Ms. Alleva. “Some of us have lost trust in health care professionals as a result of our experience.”
“It’s a huge feeling of institutional betrayal,” said Grace.
A version of this article first appeared on Medscape.com.
FDA approves upadacitinib for ulcerative colitis
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
Don’t drink calories: Artificial sweeteners beat sugar in new analysis
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript of Impact Factor with F. Perry Wilson has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
When I counsel patients who are trying to lose weight, there is something I always discuss: “Don’t drink calories.” The idea is that it is so easy to consume sweetened beverages (and alcoholic ones, for that matter) and we don’t really get a sense of how many calories we’re taking in.
Some patients balk at the idea, saying they can’t stand the taste of water or just can’t bring themselves to drink it. While, as a nephrologist, this pains me deeply to hear, I often suggest going for low- or zero-calorie flavored drinks instead of the sugary stuff.
And yet ... I need to admit that recently I’ve been more nervous about that advice. A very nice study in Nature, for example, found that artificial sweeteners induce glucose intolerance and weight gain – in mice.
Several observational studies have suggested that the use of nonnutritive sweeteners – sucralose, aspartame, and so on – are associated with higher body weight and type 2 diabetes. Of course,
Randomized trials, as ever, are the key to deeper understanding, but most trials in this space are relatively small. That makes a good case for this study, appearing in JAMA Network Open, which combines data from 17 randomized trials to determine what effects substituting sugary drinks with low- and zero-calorie drinks truly has.
So, what’s the bottom line? Should I ditch the Splenda in my morning coffee and drop in some sugar cubes?
It turns out that the effects of drinking low- or zero-calorie drinks instead of sugary ones is modest, but overall beneficial, depending on the outcome you’re trying to achieve.
Randomized trials show that switching to low-cal drinks reduces body weight by about a kilogram, and BMI by 0.3 points. It also reduces body fat by about half a percent.
Effects on glucose homeostasis – hemoglobin A1c level and fasting glucose – were not that impressive, though.
The authors also compared sugar-sweetened beverages with plain old water. I expected this analysis to show more dramatic benefits. After all, we’re all just ugly, giant bags of mostly water. Interestingly, the effects of switching to water were not as dramatic and largely nonsignificant with respect to most outcomes evaluated.
So, what do we make of this? If someone is a habitual drinker of sugar-sweetened beverages, is it preferable to switch to a zero-calorie flavored drink, compared with plain water?
One possibility is that in the trials where people are randomized to switch to water, they aren’t as adherent. Just because we ask someone to drink water doesn’t mean they do it, and so there may be a tendency to “cheat” with sugar-sweetened beverages. However, if told that low- or zero-calorie flavored drinks are okay, maybe it’s easier to stick to the plan? This is essentially the argument you get from people who say that vaping is a good way to quit smoking. It may or may not be true.
It could also be that we just don’t have enough rigorous data to make a firm conclusion. Of the 17 trials examined, only three of them used water substitution as an intervention.
All in all, these data provide some reassurance that the zero-calorie sweeteners aren’t secretly exacerbating the obesity epidemic. I’d certainly rather my patients drink Diet Coke than regular Coke. That said, these studies are necessarily short term; the longer-term effects of sugar substitutes, while perhaps not as bad as the long-term effects of sugar, must necessarily be worse than the long-term effects of drinking water. Maybe this is the nephrologist in me talking again, but I doubt that there could possibly be a fluid better for the human body than good old H2O. Except coffee, of course.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale University’s Clinical and Translational Research Accelerator. He disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.