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‘Top’ surgery for trans youth: Advance or dangerous medicine?
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Is the gender-affirmative treatment approach an example of “medicine continuing on its progressive march of improving human life” or “a manifestation of dangerous medicine that ... will cause more harm than benefit to vulnerable youths?” wonders an Australian psychiatrist in a newly published letter that addresses the controversial procedure of masculinizing chest surgery – a double mastectomy – in young people with gender dysphoria (GD).
Alison Clayton, MBBS, explores the evidence for masculinizing chest surgery and looks back at examples of “dangerous medicine” in the past century while looking forward, wondering how future medics will retrospectively view gender affirmative treatment, especially so-called “top” or masculinizing chest surgery, which is in actual fact a double mastectomy, in a letter published Nov. 22 in the Archives of Sexual Behavior.
“It is surprising that clinicians and researchers claim chest surgery for GD youth is an evidence-based intervention, rather than acknowledging it is an experimental treatment that requires more rigorous and human research ethics committee [HREC] approved research,” she writes.
“The medical profession needs to consider whether, in its championing of the gender-affirmative approach for GD youth, it is also acting brashly and making mistakes that will negatively impact some young people for the rest of their lives,” she continues.
Ms. Clayton, after many years of experience as a psychiatrist, has recently returned to postgraduate research into the history of 20th-century psychiatry at the School of Historical and Philosophical Studies, University of Melbourne.
Meanwhile, the authors of a viewpoint published online Dec. 1 in JAMA Surgery, agree with Ms. Clayton on the issue of a lack of long-term studies on which to base decisions, particularly when it comes to insurance coverage for gender surgeries in the United States.
Nnenaya Agochukwu-Mmonu, MD, and colleagues recommend use of the coverage with evidence development (CED) approach, which would, they say, provide a “rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.”
Threefold increase in gender-affirming surgeries in past decade
There has been a threefold rise in the rate of gender-affirming surgeries in the United States in the past decade, which can be attributed to increased recognition of gender dysphoria, decreasing social stigma toward these individuals, greater clinical experience, and expanding insurance coverage, according to Dr. Agochukwu-Mmonu, of the department of urology, NYU School of Medicine, and coauthors.
Ms. Clayton meanwhile notes that of the increasing number of adolescents being referred for treatment for gender dysphoria in the Western world, most were born female and many have “a history of psychiatric illness or neurodevelopmental disorders.”
Many of these youngsters also show a “high demand” for surgical removal of breasts, she adds, noting that this operation is being undertaken as routine treatment in patients as young as 13, with some clinicians arguing that “this surgery is an evidence-based intervention that improves mental health outcomes, and that it is discriminatory for it not to be available.”
She also notes that “chest dysphoria” is “a recently created term meaning discomfort with one’s breasts.” The term “breast” is therefore largely absent in publications talking about this surgery as it “may cause distress for transgender males,” to quote one source, Ms. Clayton says, and “this seems part of a broader pattern of removing this term from clinical language,” according to another article on the subject.
Ms. Clayton also says, “There are only a handful of published studies focusing on the potential benefits of masculinizing chest surgery,” and notes that these mostly report on surgery for individuals younger than 21 years old.
Significant methodological flaws in existing research
One study of 14 postsurgical youth (nine of whom were under 18 years) found that “all reported high aesthetic satisfaction and most self-reported low complication rates and improvement in mood.”
Another cross-sectional retrospective survey looked at 68 postsurgical transmasculine youth (72% of the eligible postsurgical population); 49% had surgery when younger than age 18, with the youngest being age 13 and the oldest age 24. At the time of the survey, only 14% of participants were more than 2 years postsurgery. The postsurgical participants were found to have reduced chest dysphoria (the outcome) compared with a convenience and nonmatched comparison sample of nonsurgical transmasculine youth.
And a 2021 qualitative study of 30 transmale youth – about half of whom had undergone chest surgery – concluded that the postsurgical cohort experienced “tremendous” benefits in chest dysphoria and a range of psychological outcomes.
On this particular study, Ms. Clayton notes that “in my opinion, they did not provide enough detail for the reader to make an informed judgment regarding this latter claim.”
She goes on to discuss genital surgery, sometimes called full gender-affirming surgery (or “bottom surgery”), and says proponents of these operations point out that the main objections to them in minors is to “surgical sterilization, and people get super worked up about that ... it is a barrier we have to overcome, and I think we are going to.”
Ms. Clayton asserts that it seems “this barrier is already being overcome, as it has been reported that in the United States, genital surgery is being undertaken on gender dysphoric minors as young as 15 years old.”
Reflecting on the available evidence, Ms. Clayton highlights the significant methodological flaws that limit the extent to which surgery can be linked to short-term improved mental health outcomes and adds that information on long-term outcomes and rates of regret is unavailable.
She also asserts that the research fails to assess “a role for psychological interventions which could be utilized, as a least-harm intervention, until maturity is reached.”
Historical examples of experimental medicine
Ms. Clayton goes on to draw parallels with experimental medicine performed on homosexuals in the 20th century, highlighting the medical and surgical interventions, which included metrazol convulsive therapy, chemical castration with estrogens, surgical castration, clitoridectomy, brain operations, and aversive electrotherapy.
She also refers to the historical practice of hormonal treatment for “tall girls” and “short boys” between the 1960s and 1980s. Hormones were given to young people who did not have any medical reason underpinning their stature but were distressed, and society considered their height to have a negative social impact.
“With the encouragement of physicians and school nurses, enthusiastic media promotion, and pharmaceutical companies’ advertising, parents sought hormonal interventions,” she writes, adding that, at the time the hormones were considered safe, but long-term adverse effects emerged, including impaired fertility and increased risk of cancers.
“This seems another part of the story of medicine acting to reinforce society’s sex stereotypes, and for some patients it came at disastrous personal cost,” writes Ms. Clayton.
The gender-affirming approach is based on endorsing the adolescent’s stated gender identity with minimal questioning and “that they should be supported to undertake social transition, medical transition, masculinizing chest surgery, and, some also argue, genital surgery,” she writes.
Objectors to this approach pinpoint the “limited and low-quality evidence base for the benefits” but also “the irreversible and long-term adverse impacts of these treatments on fertility and sexual function, as well as on bone, brain, and cardiovascular functioning.”
Current studies of gender-affirming surgeries lack standardization
In their viewpoint, Dr. Agochukwu-Mmonu and colleagues state that use of a CED would not only help provide an evidence base but would also ensure better-informed policy access and coverage decisions to help standardize approaches to gender surgery in the United States.
Currently, they note, “Studies examining the mental health benefit for patients undergoing gender-affirming surgeries include measures that lack standardization, evaluate different interventions (that is, surgeries are rarely done with concurrent hormone administration), include dissimilar patient populations, and use different study designs.”
This difference in study design leads to variation in reported outcomes. Although many studies have shown benefit, others report that patients have unrealistic expectations or experience regret, Dr. Agochukwu-Mmonu and coauthors conclude.
CED provides an option that would enable informed decisions. “It allows the deliberate use of innovative therapies, explicit integration of transgender and nonbinary patient input, and ongoing systematic evaluation aimed to identify specific patient groups who would or would not benefit from their use.”
This leads back to Ms. Clayton’s central question around whether the gender-affirmative approach is a medical advance or dangerous medicine.
“Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits being implemented outside HREC-regulated clinical trial settings?’” she wonders.
Ms. Clayton has declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
Bullae on elderly woman’s toes
A biopsy was performed and sent for immunofluorescence; the results were negative. This, along with the patient’s history of diabetes, led us to the diagnosis of bullosis diabeticorum (BD). This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes.
The etiology of BD is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites.
A diagnosis of BD can be made when biopsy with immunofluorescence excludes other histologically similar diagnoses such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And, while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported.1,2 Cultures are warranted only if a secondary infection is suspected.
The distribution of lesions and the presence—or absence—of systemic symptoms go a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy.3 Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.3
The blisters associated with BD spontaneously resolve over several weeks without treatment but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection. For this patient, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.
This case was adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman’s toes. J Fam Pract. 2014;63:273-274.
1. James WD, Odom RB, Goette DK. Bullous eruption of diabetes. A case with positive immunofluorescence microscopy findings. Arch Dermatol. 1980;116:1191-1192.
2. Basarab T, Munn SE, McGrath J, et al. Bullous diabeticorum. A case report and literature review. Clin Exp Dermatol. 1995;20:218-220. doi: 10.1111/j.1365-2230.1995.tb01305.x
3. Hull C, Zone JJ. Approach to the patient with cutaneous blisters. UpToDate. Updated July 30, 2019. Accessed September 14, 2021. www.uptodate.com/contents/approach-to-the-patient-with-cutaneous-blisters
A biopsy was performed and sent for immunofluorescence; the results were negative. This, along with the patient’s history of diabetes, led us to the diagnosis of bullosis diabeticorum (BD). This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes.
The etiology of BD is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites.
A diagnosis of BD can be made when biopsy with immunofluorescence excludes other histologically similar diagnoses such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And, while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported.1,2 Cultures are warranted only if a secondary infection is suspected.
The distribution of lesions and the presence—or absence—of systemic symptoms go a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy.3 Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.3
The blisters associated with BD spontaneously resolve over several weeks without treatment but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection. For this patient, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.
This case was adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman’s toes. J Fam Pract. 2014;63:273-274.
A biopsy was performed and sent for immunofluorescence; the results were negative. This, along with the patient’s history of diabetes, led us to the diagnosis of bullosis diabeticorum (BD). This condition, also known as bullous disease of diabetes, is characterized by abrupt development of noninflammatory bullae on acral areas in patients with diabetes.
The etiology of BD is unknown. The acral location suggests that trauma may be a contributing factor. Although electron microscopy has suggested an abnormality in anchoring fibrils, this cellular change does not fully explain the development of multiple blisters at varying sites.
A diagnosis of BD can be made when biopsy with immunofluorescence excludes other histologically similar diagnoses such as epidermolysis bullosa, noninflammatory bullous pemphigoid, and porphyria cutanea tarda. And, while immunofluorescence findings are typically negative, elevated levels of immunoglobulin M and C3 have, on occasion, been reported.1,2 Cultures are warranted only if a secondary infection is suspected.
The distribution of lesions and the presence—or absence—of systemic symptoms go a long way toward narrowing the differential of blistering diseases. The presence of generalized blistering and systemic symptoms would suggest conditions related to medication exposure, such as Stevens-Johnson syndrome or toxic epidermal necrolysis; infectious etiologies (eg, staphylococcal scalded skin syndrome); autoimmune causes; or underlying malignancy.3 Generalized blistering in the absence of systemic symptoms would support diagnoses such as bullous impetigo and pemphigoid.3
The blisters associated with BD spontaneously resolve over several weeks without treatment but tend to recur. The lesions typically heal without significant scarring, although they may have a darker pigmentation after the first occurrence. Treatment may be warranted if a patient develops a secondary infection. For this patient, the bullae resolved within 2 weeks without treatment, although mild hyperpigmentation remained.
This case was adapted from: Mims L, Savage A, Chessman A. Blisters on an elderly woman’s toes. J Fam Pract. 2014;63:273-274.
1. James WD, Odom RB, Goette DK. Bullous eruption of diabetes. A case with positive immunofluorescence microscopy findings. Arch Dermatol. 1980;116:1191-1192.
2. Basarab T, Munn SE, McGrath J, et al. Bullous diabeticorum. A case report and literature review. Clin Exp Dermatol. 1995;20:218-220. doi: 10.1111/j.1365-2230.1995.tb01305.x
3. Hull C, Zone JJ. Approach to the patient with cutaneous blisters. UpToDate. Updated July 30, 2019. Accessed September 14, 2021. www.uptodate.com/contents/approach-to-the-patient-with-cutaneous-blisters
1. James WD, Odom RB, Goette DK. Bullous eruption of diabetes. A case with positive immunofluorescence microscopy findings. Arch Dermatol. 1980;116:1191-1192.
2. Basarab T, Munn SE, McGrath J, et al. Bullous diabeticorum. A case report and literature review. Clin Exp Dermatol. 1995;20:218-220. doi: 10.1111/j.1365-2230.1995.tb01305.x
3. Hull C, Zone JJ. Approach to the patient with cutaneous blisters. UpToDate. Updated July 30, 2019. Accessed September 14, 2021. www.uptodate.com/contents/approach-to-the-patient-with-cutaneous-blisters
Clinical Edge Journal Scan Commentary: Psoriasis December 2021
A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).
With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).
While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).
These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.
A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).
With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).
While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).
These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.
A retrospective observational study of nearly 1200 prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411), both of which inhibit IL-17A, examined drug persistence after 18 months. Ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab. Both drugs are dosed monthly after an initial loading dose (Blauvelt A et al. Dermatol Ther (Heidelb).
With several biologic options available, patients may be switched from one biologic to another if they are not having an adequate response. Separate studies have shown that patients with an inadequate response to ustekinumab are likely to have a better response when switched to brodalumab or guselkumab, although this does not tell us if one is more likely to be effective than the other. In a recent matching-adjusted indirect comparison study using data for patients with psoriasis who responded inadequately to ustekinumab and switched to receive brodalumab (n=121) or guselkumab (n=135) the authors found that brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab with a PASI 100 rate at week 36 of 40.3% for brodalumab vs 20.0% for guselkumab; P < 0.001. (Hampton P et al. Psoriasis (Auckl).
While biologics have revolutionized the treatment of psoriasis, not all patients with extensive disease desire or are appropriate for a systemic therapy. Topical steroids, the most commonly used topical psoriasis therapy, still carry some risk of systemic absorption and are associate with cutaneous side effects such as atrophy with prolonged use. Tarpinarof 1% cream is a novel aryl hydrocarbon receptor modulating agent that has been shown in phase 3 studies to be an effective treatment for psoriasis when applied once a day. A recent open label study of 21 adult patients with extensive plaque psoriasis (20% or more body surface area (BSA) involvement, mean baseline BSA 27.2%) who applied tapinarof cream 1% QD daily showed that 94.7% of patients had a decrease in their PASI score (mean PASI decrease of 59.6%). Despite the large BSA being treated, tapinarof plasma concentration were low and remained below the quantification level in the majority (67.9%) of samples tested. There were also no concerning EKG changes such as QT prolongation. Folliculitis and headache were the most common adverse events (each reported by 4 patients) (Jett JE et al. Am J Clin Dermatol).
These studies all provide valuable data in helping us to make the best treatment decisions for patients with moderate to severe plaque psoriasis.
HPV vaccines reduce cervical cancer rates in young females
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
Two different studies have found that, provided young females are immunized with the human papilloma virus (HPV) vaccine at a young enough age, both the incidence of and mortality from cervical cancer can be dramatically curtailed, data from the United Kingdom and to a lesser extent, the United States indicate.
In the U.K. study, published online in The Lancet, researchers showed that the national vaccination program against HPV, initiated in England in 2008, has all but eradicated cervical cancer and cervical intraepithelial neoplasia (CIN3) in young girls who received the vaccine at the age of 12 and 13 years (school year 8) prior to their sexual debut.
In this age group, cervical cancer rates were 87% lower than rates among previously nonvaccinated generations, while CIN3 rates were reduced by 97%, as researchers report. “It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding,” he added.
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, UK Health Security Agency, London, said in the same statement.
“This represents an important step forward in cervical cancer prevention, and we hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” she added.
Vanessa Saliba, MD, a consultant epidemiologist for the UK Health Security Agency, agreed, adding that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.”
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she reemphasized.
British HPV program
When initiated in 2008, the national HPV vaccination program used the bivalent, Cervarix vaccine against HPV 16 and 18. As researchers noted, these two HPV types are responsible for 70%-80% of all cervical cancers in England.
However, in 2012, the program switched to the quadrivalent HPV vaccine (Gardasil) which is also effective against two additional HPV types, 6 and 11, both of which cause genital warts. The program also originally recommended the three-dose regimen for both HPV vaccines.
Now, only two doses of the vaccine are given to girls under the age of 15 even though it has been shown that a single dose of the HPV vaccine provides good protection against persistent infection, with efficacy rates that are similar to that of three doses, as the authors point out.
Among the cohort eligible for vaccination at 12 or 13 years of age, 89% received at least one dose of the HPV vaccine while 85% of the same age group received all three shots.
Cancer registry
Data from a population-based cancer registry was used to estimate the early effect of the bivalent HPV program on the incidence of cervical cancer and CIN3 in England between January 2006 and June 2019. During the study interval, there were 27,946 diagnoses of cervical cancer and 318,058 diagnoses of CIN3, lead author Milena Falcaro, MD, King’s College London, and colleagues report. Participants were then analyzed separately according to their age at the time of vaccination and the incidence rates calculated for both cervical cancer and CIN3 in the three separate groups.
For slightly older girls who received the vaccine between 14 and 16 years of age (school year 10-11), cervical cancer was reduced by 62% while CIN3 rates were reduced by 75%. For those who received the vaccine between 16 and 18 years of age (school year 12-13), cervical cancer rates were reduced by 34% while CIN3 rates were reduced by 39%, study authors add.
Indeed, the authors estimate that by June 2019 there were approximately 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would otherwise have been expected in the vaccinated population in England.
The authors acknowledge that cervical cancer is rare in young women and vaccinated populations are still young. For example, the youngest recipients would have been immunized at the age of 12 in 2008 and would still be only 23 years old in 2019 when the study ended.
Thus, the authors emphasize that, because the vaccinated populations are still young, it’s too early to assess the full effect of HPV vaccination on cervical cancer rates.
Asked to comment on the study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, pointed out that results from the British study are very similar to those from a Swedish study assessing the effect of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. As an oncologist who has been treating cervical cancer for 40 years – particularly advanced cervical cancer – “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful,” he stressed.
Editorial commentary
Commenting on the findings, editorialists Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania, point out that published reports evaluating the effect of HPV vaccination on cervical cancer rates have been scarce until now.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by the WHO [World Health Organization],” the editorialists add.
Dr. Cruickshank and Dr. Grigore also suggest that the effect HPV vaccination is having on cervical cancer rates as shown in this study should also stimulate vaccination programs in low- and middle-income countries where cervical cancer is a far greater public health issue than it is in countries with established systems of vaccination and screening.
HPV vaccination in the United States
The HPV vaccination program is similarly reducing the incidence of and mortality from cervical cancer among younger women in the United States who are most likely to have received the vaccine. As reported by lead author, Justin Barnes, MD, Washington University, St. Louis, the incidence of cervical cancer dropped by 37.7% from 2001 through 2005 to 2010 through 2017 in girls and young women between 15 and 24 years of age.
The U.S. study was published online in JAMA Pediatrics.
“HPV vaccine coverage in the U.S. has improved over the last few years although it was quite poor for many years,” senior author of the U.K. study, Peter Sasieni, MD, King’s College London, said in an interview. “Thus, one would anticipate a lower impact on the population in the U.S., because vaccine uptake, particularly in those aged 11-14 years was so much lower than it was in the U.K.,” he noted.
SEER databases
National age-adjusted cervical cancer incidence and mortality data from January 2001 through December 2017 for women and girls between 15 and 39 years of age were obtained from the combined Surveillance, Epidemiology, and End Results as well as the National Program of Cancer Registries databases. Mortality data was obtained from the National Center for Health Statistics.
Investigators then compared percentage changes in the incidence of and mortality from cervical cancer from January 2001 through December 2005 during the prevaccination years to that observed between January 2010 through December 2017 during the postvaccination years. They also compared incidence and mortality rates in three different cohorts: females between 15 and 24 years of age, those between 25 and 29 years of age, and those between 30 and 39 years of age.
“The older two groups were included as comparison, given their low vaccination rates,” the authors explained. Results showed that, during the same study interval from 2001 through 2005 to 2010 through 2017, the incidence of cervical cancer dropped by only 16.1% in women between 25 and 29 years of age and by only 8% for women between 30 and 39 years of age, the investigators report.
Reductions in mortality from cervical cancer were only strikingly so in the youngest age group of females between 15 and 24 years of age, among whom there was a 43.3% reduction in mortality from 2001-2005 to 2010-2017, as Dr. Barnes and colleagues note.
This pattern changed substantially in women between the ages of 25 and 29, among whom there was a 4.3% increase in mortality from cervical cancer during the same study interval and a small, 4.7% reduction among women between 30 and 39 years of age, investigators add. In actual numbers, mortality rates from cervical cancer were very low at only 0.6 per 100,000 in females between 15 and 24 years of age.
This compared to a mortality rate of 0.57 per 100,000 in women between 25 and 29 years of age and 1.89 per 100,000 in the oldest age group. “These nationwide data showed decreased cervical cancer incidence and mortality among women and girls aged 15-24 years after HPV vaccine introduction,” Dr. Barnes notes.
“Thus, the current study adds to knowledge by quantitatively comparing changes in cervical cancer incidence by age-based vaccine eligibility and providing suggestive evidence for vaccine-associated decreases in cervical cancer mortality,” investigators add.
However, as the authors also point out, while the reduction in mortality from cervical cancer associated with HPV vaccination may translate to older age groups as HPV-vaccinated cohorts age, “the number of deaths and hence the number of potentially averted deaths in young women and girls was small,” they caution, “and efforts to further improve vaccination uptake remain important.”
None of the authors or the editorialists had any conflicts of interest to declare.
For older adults, smelling the roses may be more difficult
Young and old alike are affected – more than 80%-90% of those diagnosed with the virus, according to some estimates. While most people recover in a few months, 16% take half a year or longer to do so, research has found. According to new estimates, up to 1.6 million Americans have chronic olfactory dysfunction due to COVID-19.
Seniors are especially vulnerable, experts suggest. “We know that many older adults have a compromised sense of smell to begin with. Add to that the insult of COVID, and it made these problems worse,” said Dr. Jayant Pinto, professor of surgery and a specialist in sinus and nasal diseases at the University of Chicago Medical Center.
Recent data highlight the interaction between COVID-19, advanced age, and loss of smell. When Italian researchers evaluated 101 patients who’d been hospitalized for mild to moderate COVID-19, 50 showed objective signs of smell impairment 6 months later. Those 65 or older were nearly twice as likely to be impaired; those 75 or older were more than 2½ times as likely.
Most people aren’t aware of the extent to which smell can be diminished in later life. More than half of 65- to 80-year-olds have some degree of smell loss, or olfactory dysfunction, as it’s known in the scientific literature. That rises to as high as 80% for those even older. People affected often report concerns about safety, less enjoyment eating, and an impaired quality of life.
But because the ability to detect, identify, and discriminate among odors declines gradually, most older adults – up to 75% of those with some degree of olfactory dysfunction – don’t realize they’re affected.
A host of factors are believed to contribute to age-related smell loss, including a reduction in the number of olfactory sensory neurons in the nose, which are essential for detecting odors; changes in stem cells that replenish these neurons every few months; atrophy of the processing center for smell in the brain, called the olfactory bulb; and the shrinkage of brain centers closely connected with the olfactory bulb, such as the hippocampus, a region central to learning and memory.
Also, environmental toxic substances such as air pollution play a part, research shows. “Olfactory neurons in your nose are basically little pieces of your brain hanging out in the outside world,” and exposure to them over time damages those neurons and the tissues that support them, explained Pamela Dalton, PhD, a principal investigator at the Monell Chemical Senses Center, a smell and taste research institute in Philadelphia.
Still, the complex workings of the olfactory system have not been mapped in detail yet, and much remains unknown, said Dr. Sandeep Robert Datta, professor of neurobiology at Harvard Medical School, Boston.
“We tend to think of our sense of smell as primarily aesthetic,” he said. “What’s very clear is that it’s far more important. The olfactory system plays a key role in maintaining our emotional well-being and connecting us with the world.”
Dr. Datta experienced this after having a bone marrow transplant followed by chemotherapy years ago. Unable to smell or taste food, he said, he felt “very disoriented” in his environment.
Common consequences of smell loss include a loss of appetite (without smell, taste is deeply compromised), difficulty monitoring personal hygiene, depression, and an inability to detect noxious fumes. In older adults, this can lead to weight loss, malnutrition, frailty, inadequate personal care, and accidents caused by gas leaks or fires.
Jerome Pisano, 75, of Bloomington, Ill., has been living with smell loss for 5 years. Repeated tests and consultations with physicians haven’t pinpointed a reason for this ailment, and sometimes he feels “hopeless,” he admitted.
Before he became smell-impaired, Mr. Pisano was certified as a wine specialist. He has an 800-bottle wine cellar. “I can’t appreciate that as much as I’d like. I miss the smell of cut grass. Flowers. My wife’s cooking,” he said. “It certainly does decrease my quality of life.”
Smell loss is also associated in various research studies with a higher risk of death for older adults. One study, authored by Dr. Pinto and colleagues, found that older adults with olfactory dysfunction were nearly three times as likely to die over a period of 5 years as were seniors whose sense of smell remained intact.
“Our sense of smell signals how our nervous system is doing and how well our brain is doing overall,” Dr. Pinto said. According to a review published earlier this year, 90% of people with early-stage Parkinson’s disease and more than 80% of people with Alzheimer’s disease have olfactory dysfunction – a symptom that can precede other symptoms by many years.
There is no treatment for smell loss associated with neurological illness or head trauma, but if someone has persistent sinus problems or allergies that cause congestion, an over-the-counter antihistamine or nasal steroid spray can help. Usually, smell returns in a few weeks.
For smell loss following a viral infection, the picture is less clear. It’s not known, yet, which viruses are associated with olfactory dysfunction, why they damage smell, and what trajectory recovery takes. COVID-19 may help shine a light on this since it has inspired a wave of research on olfaction loss around the world.
“What characteristics make people more vulnerable to a persistent loss of smell after a virus? We don’t know that, but I think we will because that research is underway and we’ve never had a cohort [of people with smell loss] this large to study,” said Dr. Dalton, of the Monell center.
Some experts recommend smell training, noting evidence of efficacy and no indication of harm. This involves sniffing four distinct scents (often eucalyptus, lemon, rose, and cloves) twice a day for 30 seconds each, usually for 4 weeks. Sometimes the practice is combined with pictures of the items being smelled, a form of visual reinforcement.
The theory is that “practice, practice, practice” will stimulate the olfactory system, said Charles Greer, PhD, professor of neurosurgery and neuroscience at Yale University, New Haven, Conn. Although scientific support isn’t well established, he said, he often recommends that people who think their smell is declining “get a shelf full of spices and smell them on a regular basis.”
Richard Doty, PhD, director of the University of Pennsylvania’s Smell and Taste Center, remains skeptical. He’s writing a review of smell training and notes that 20%-30% of people with viral infections and smell loss recover in a relatively short time, whether or not they pursue this therapy.
“The main thing we recommend is avoid polluted environments and get your full complement of vitamins,” since several vitamins play an important role in maintaining the olfactory system, he said.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Young and old alike are affected – more than 80%-90% of those diagnosed with the virus, according to some estimates. While most people recover in a few months, 16% take half a year or longer to do so, research has found. According to new estimates, up to 1.6 million Americans have chronic olfactory dysfunction due to COVID-19.
Seniors are especially vulnerable, experts suggest. “We know that many older adults have a compromised sense of smell to begin with. Add to that the insult of COVID, and it made these problems worse,” said Dr. Jayant Pinto, professor of surgery and a specialist in sinus and nasal diseases at the University of Chicago Medical Center.
Recent data highlight the interaction between COVID-19, advanced age, and loss of smell. When Italian researchers evaluated 101 patients who’d been hospitalized for mild to moderate COVID-19, 50 showed objective signs of smell impairment 6 months later. Those 65 or older were nearly twice as likely to be impaired; those 75 or older were more than 2½ times as likely.
Most people aren’t aware of the extent to which smell can be diminished in later life. More than half of 65- to 80-year-olds have some degree of smell loss, or olfactory dysfunction, as it’s known in the scientific literature. That rises to as high as 80% for those even older. People affected often report concerns about safety, less enjoyment eating, and an impaired quality of life.
But because the ability to detect, identify, and discriminate among odors declines gradually, most older adults – up to 75% of those with some degree of olfactory dysfunction – don’t realize they’re affected.
A host of factors are believed to contribute to age-related smell loss, including a reduction in the number of olfactory sensory neurons in the nose, which are essential for detecting odors; changes in stem cells that replenish these neurons every few months; atrophy of the processing center for smell in the brain, called the olfactory bulb; and the shrinkage of brain centers closely connected with the olfactory bulb, such as the hippocampus, a region central to learning and memory.
Also, environmental toxic substances such as air pollution play a part, research shows. “Olfactory neurons in your nose are basically little pieces of your brain hanging out in the outside world,” and exposure to them over time damages those neurons and the tissues that support them, explained Pamela Dalton, PhD, a principal investigator at the Monell Chemical Senses Center, a smell and taste research institute in Philadelphia.
Still, the complex workings of the olfactory system have not been mapped in detail yet, and much remains unknown, said Dr. Sandeep Robert Datta, professor of neurobiology at Harvard Medical School, Boston.
“We tend to think of our sense of smell as primarily aesthetic,” he said. “What’s very clear is that it’s far more important. The olfactory system plays a key role in maintaining our emotional well-being and connecting us with the world.”
Dr. Datta experienced this after having a bone marrow transplant followed by chemotherapy years ago. Unable to smell or taste food, he said, he felt “very disoriented” in his environment.
Common consequences of smell loss include a loss of appetite (without smell, taste is deeply compromised), difficulty monitoring personal hygiene, depression, and an inability to detect noxious fumes. In older adults, this can lead to weight loss, malnutrition, frailty, inadequate personal care, and accidents caused by gas leaks or fires.
Jerome Pisano, 75, of Bloomington, Ill., has been living with smell loss for 5 years. Repeated tests and consultations with physicians haven’t pinpointed a reason for this ailment, and sometimes he feels “hopeless,” he admitted.
Before he became smell-impaired, Mr. Pisano was certified as a wine specialist. He has an 800-bottle wine cellar. “I can’t appreciate that as much as I’d like. I miss the smell of cut grass. Flowers. My wife’s cooking,” he said. “It certainly does decrease my quality of life.”
Smell loss is also associated in various research studies with a higher risk of death for older adults. One study, authored by Dr. Pinto and colleagues, found that older adults with olfactory dysfunction were nearly three times as likely to die over a period of 5 years as were seniors whose sense of smell remained intact.
“Our sense of smell signals how our nervous system is doing and how well our brain is doing overall,” Dr. Pinto said. According to a review published earlier this year, 90% of people with early-stage Parkinson’s disease and more than 80% of people with Alzheimer’s disease have olfactory dysfunction – a symptom that can precede other symptoms by many years.
There is no treatment for smell loss associated with neurological illness or head trauma, but if someone has persistent sinus problems or allergies that cause congestion, an over-the-counter antihistamine or nasal steroid spray can help. Usually, smell returns in a few weeks.
For smell loss following a viral infection, the picture is less clear. It’s not known, yet, which viruses are associated with olfactory dysfunction, why they damage smell, and what trajectory recovery takes. COVID-19 may help shine a light on this since it has inspired a wave of research on olfaction loss around the world.
“What characteristics make people more vulnerable to a persistent loss of smell after a virus? We don’t know that, but I think we will because that research is underway and we’ve never had a cohort [of people with smell loss] this large to study,” said Dr. Dalton, of the Monell center.
Some experts recommend smell training, noting evidence of efficacy and no indication of harm. This involves sniffing four distinct scents (often eucalyptus, lemon, rose, and cloves) twice a day for 30 seconds each, usually for 4 weeks. Sometimes the practice is combined with pictures of the items being smelled, a form of visual reinforcement.
The theory is that “practice, practice, practice” will stimulate the olfactory system, said Charles Greer, PhD, professor of neurosurgery and neuroscience at Yale University, New Haven, Conn. Although scientific support isn’t well established, he said, he often recommends that people who think their smell is declining “get a shelf full of spices and smell them on a regular basis.”
Richard Doty, PhD, director of the University of Pennsylvania’s Smell and Taste Center, remains skeptical. He’s writing a review of smell training and notes that 20%-30% of people with viral infections and smell loss recover in a relatively short time, whether or not they pursue this therapy.
“The main thing we recommend is avoid polluted environments and get your full complement of vitamins,” since several vitamins play an important role in maintaining the olfactory system, he said.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Young and old alike are affected – more than 80%-90% of those diagnosed with the virus, according to some estimates. While most people recover in a few months, 16% take half a year or longer to do so, research has found. According to new estimates, up to 1.6 million Americans have chronic olfactory dysfunction due to COVID-19.
Seniors are especially vulnerable, experts suggest. “We know that many older adults have a compromised sense of smell to begin with. Add to that the insult of COVID, and it made these problems worse,” said Dr. Jayant Pinto, professor of surgery and a specialist in sinus and nasal diseases at the University of Chicago Medical Center.
Recent data highlight the interaction between COVID-19, advanced age, and loss of smell. When Italian researchers evaluated 101 patients who’d been hospitalized for mild to moderate COVID-19, 50 showed objective signs of smell impairment 6 months later. Those 65 or older were nearly twice as likely to be impaired; those 75 or older were more than 2½ times as likely.
Most people aren’t aware of the extent to which smell can be diminished in later life. More than half of 65- to 80-year-olds have some degree of smell loss, or olfactory dysfunction, as it’s known in the scientific literature. That rises to as high as 80% for those even older. People affected often report concerns about safety, less enjoyment eating, and an impaired quality of life.
But because the ability to detect, identify, and discriminate among odors declines gradually, most older adults – up to 75% of those with some degree of olfactory dysfunction – don’t realize they’re affected.
A host of factors are believed to contribute to age-related smell loss, including a reduction in the number of olfactory sensory neurons in the nose, which are essential for detecting odors; changes in stem cells that replenish these neurons every few months; atrophy of the processing center for smell in the brain, called the olfactory bulb; and the shrinkage of brain centers closely connected with the olfactory bulb, such as the hippocampus, a region central to learning and memory.
Also, environmental toxic substances such as air pollution play a part, research shows. “Olfactory neurons in your nose are basically little pieces of your brain hanging out in the outside world,” and exposure to them over time damages those neurons and the tissues that support them, explained Pamela Dalton, PhD, a principal investigator at the Monell Chemical Senses Center, a smell and taste research institute in Philadelphia.
Still, the complex workings of the olfactory system have not been mapped in detail yet, and much remains unknown, said Dr. Sandeep Robert Datta, professor of neurobiology at Harvard Medical School, Boston.
“We tend to think of our sense of smell as primarily aesthetic,” he said. “What’s very clear is that it’s far more important. The olfactory system plays a key role in maintaining our emotional well-being and connecting us with the world.”
Dr. Datta experienced this after having a bone marrow transplant followed by chemotherapy years ago. Unable to smell or taste food, he said, he felt “very disoriented” in his environment.
Common consequences of smell loss include a loss of appetite (without smell, taste is deeply compromised), difficulty monitoring personal hygiene, depression, and an inability to detect noxious fumes. In older adults, this can lead to weight loss, malnutrition, frailty, inadequate personal care, and accidents caused by gas leaks or fires.
Jerome Pisano, 75, of Bloomington, Ill., has been living with smell loss for 5 years. Repeated tests and consultations with physicians haven’t pinpointed a reason for this ailment, and sometimes he feels “hopeless,” he admitted.
Before he became smell-impaired, Mr. Pisano was certified as a wine specialist. He has an 800-bottle wine cellar. “I can’t appreciate that as much as I’d like. I miss the smell of cut grass. Flowers. My wife’s cooking,” he said. “It certainly does decrease my quality of life.”
Smell loss is also associated in various research studies with a higher risk of death for older adults. One study, authored by Dr. Pinto and colleagues, found that older adults with olfactory dysfunction were nearly three times as likely to die over a period of 5 years as were seniors whose sense of smell remained intact.
“Our sense of smell signals how our nervous system is doing and how well our brain is doing overall,” Dr. Pinto said. According to a review published earlier this year, 90% of people with early-stage Parkinson’s disease and more than 80% of people with Alzheimer’s disease have olfactory dysfunction – a symptom that can precede other symptoms by many years.
There is no treatment for smell loss associated with neurological illness or head trauma, but if someone has persistent sinus problems or allergies that cause congestion, an over-the-counter antihistamine or nasal steroid spray can help. Usually, smell returns in a few weeks.
For smell loss following a viral infection, the picture is less clear. It’s not known, yet, which viruses are associated with olfactory dysfunction, why they damage smell, and what trajectory recovery takes. COVID-19 may help shine a light on this since it has inspired a wave of research on olfaction loss around the world.
“What characteristics make people more vulnerable to a persistent loss of smell after a virus? We don’t know that, but I think we will because that research is underway and we’ve never had a cohort [of people with smell loss] this large to study,” said Dr. Dalton, of the Monell center.
Some experts recommend smell training, noting evidence of efficacy and no indication of harm. This involves sniffing four distinct scents (often eucalyptus, lemon, rose, and cloves) twice a day for 30 seconds each, usually for 4 weeks. Sometimes the practice is combined with pictures of the items being smelled, a form of visual reinforcement.
The theory is that “practice, practice, practice” will stimulate the olfactory system, said Charles Greer, PhD, professor of neurosurgery and neuroscience at Yale University, New Haven, Conn. Although scientific support isn’t well established, he said, he often recommends that people who think their smell is declining “get a shelf full of spices and smell them on a regular basis.”
Richard Doty, PhD, director of the University of Pennsylvania’s Smell and Taste Center, remains skeptical. He’s writing a review of smell training and notes that 20%-30% of people with viral infections and smell loss recover in a relatively short time, whether or not they pursue this therapy.
“The main thing we recommend is avoid polluted environments and get your full complement of vitamins,” since several vitamins play an important role in maintaining the olfactory system, he said.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Clinical Edge Journal Scan Commentary: Uterine Fibroids December 2021
A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.
When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.
A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.
When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.
A recent study by Lee et al in the Journal of Obstetrics and Gynaecology Research evaluated the feasibility of robotic single-port myomectomy (RSPM) using the da Vinci SP surgical system. In this prospective observational study, 61 women with symptomatic fibroids underwent RSPM. In women with less than 7 resected uterine fibroids (maximal diameter < 10 cm) as well as those with at least 7 resected fibroids (maximal diameter of resected fibroids ≥10 cm), there was no conversion to single-port laparoscopic myomectomy, multiport laparoscopic myomectomy, or laparotomy. Reported complications were minor and included fever, transient ileus and blood transfusion in 15 patients. The authors proposed that robotic single-port myomectomy could solve many of the ergonomic problems associated with single-port laparoscopic myomectomy.
When performing myomectomy during C-section, is there a method that is advantageous? This question was evaluated by Karaca SY et al in European Journal of Obstetrics and Gynecology and Reproductive Biology who compared transendometrial myomectomy with conventional myomectomy. Overall, 41 patients underwent transendometrial myomectomy, and 52 patients underwent conventional myomectomy, with all patients having one single anterior intramural fibroid removed. The mean duration of surgery (50.5 minutes vs 63.6 minutes; P = .001) was lower in the transendometrial group versus the conventional myomectomy group. Additionally, patients who underwent transendometrial myomectomy (0.58 ± 0.61) had significantly lower adhesion scores in their subsequent pregnancy compared to patients who underwent conventional myomectomy (1,76 ± 1,1) (P = 0.001). Length of hospital stay, procedure-related hemoglobin difference, blood transfusion requirement, and postoperative fever were similar in both groups.