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Treatment-resistant GERD reported by more than half of patients
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
SAN DIEGO – Gastroesophageal reflux disease refractory to proton pump inhibitors may affect nearly half of those treated, according to the findings of a population-based sample of more than 70,000 Americans.
As part of the National Institutes of Health GI Patient Reported Outcomes Measurement Information System (NIH GI-PROMIS) questionnaire, respondents could download a free app called “My GI Health,” which led them through a series of questions about GI diseases. Sean Delshad, MD, MBA, of Cedars-Sinai Medical Center Los Angeles, and his colleagues examined data on symptom responses about GERD and heartburn.
Their somewhat surprising findings were that 44% of respondents had ever had GERD and that 70% of those respondents had symptoms in the past week. GERD seemed to be more common in women than in men, and in non-Hispanic whites more than other demographic groups. The rate of proton pump inhibitor–refractory GERD was reported at 54%.
Dr. Delshad discussed the implications of the study results for treatment and research in a video interview at the annual Digestive Disease Week.
REPORTING FROM DDW 2019
CMS targets ‘spread pricing’ to help lower drug costs
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
The Centers for Medicare & Medicaid Services is clarifying how Medicaid and Children’s Health Insurance Program (CHIP) managed care plans calculate the medical loss ratio in a effort to reign in drug costs.
The medical loss ratio is set at 85%, meaning that managed care plans can spend only 15% of revenue on administrative costs and profits, with 85% being used for beneficiary care, including paying for claims, expenditures for activities that improve health care quality, and fraud prevention activities.
But CMS officials said they are concerned that managed care plans are not properly accounting for “spread pricing” in their medical loss ratio calculations. Spread pricing occurs when pharmacy benefit managers (PBMs) keep a portion of money paid by the managed care plan instead of passing the payment to the pharmacy for filling the prescription on behalf of the beneficiary.
“If spread pricing is not appropriately monitored and accounted for, a PBM can profit from charging health plans an excess amount above the amount paid to the pharmacy dispensing a drug, which increases Medicaid costs for taxpayers,” the agency said in a statement issued May 15 in conjunction with new guidance on calculating the medical loss ratio to account for spread pricing.
Regulations require Medicaid and CHIP managed care plans to exclude drug rebates from actual claims costs used to calculate the medical loss ratio. The new guidance clarifies the definition of a drug rebate to include “any price concession or discount received by the managed care plan or its PBM, regardless of who pays the rebate or discount,” the agency said. “Therefore, the amount retained by the PBM under spread pricing would have to be excluded from the amount of claims costs used for calculating the managed care plan’s [medical loss ratio].”
CMS added that the reason for this is that spread pricing “should not be used to artificially inflate a Medicaid or CHIP managed care plan’s [medical loss ratio].”
Enzalutamide in castration-sensitive prostate cancer and ctDNA to monitor early colorectal cancer
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).
ARCHES trial
The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.
Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.
ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.
Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
What this means in practice
It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.
It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
ctDNA in early colorectal cancer
In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.
The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.
Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.
Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.
What this means in practice
The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.
Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
Part 3: Talkin’ ’bout My Generation
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
Members of the baby boom generation (yes, my generation)—the nomenclature given to the 76 million people born between 1946 and 1964—are now in our 50s, 60s, and 70s. Many of us are enjoying our retirement while others are still working. Regardless of our circumstances, we all share one challenge: aging as comfortably as we can. It’s a fact of our lives that as we age, we battle risk factors for a variety of conditions, ranging from diabetes, heart disease, and Alzheimer disease to … sexually transmitted infections (STIs).
Ever since I saw the statistics about increasing rates of STIs among older Americans, I’ve been mulling possible explanations for this trend. In conversation with my CR colleagues, the question arose as to whether the fact that the current population of senior citizens is comprised largely of Baby Boomers has had an impact. It’s certainly worth considering!
We (the Baby Boomers) are more savvy, assertive, health-conscious, and engaged in our health care than the generations that preceded us.1,2 When I look around at my friends and colleagues, I see a group of people who want to live more active lives and remain socially engaged—even as we manage our chronic conditions! As self-determining patients, we are likely to question established principles of medical care, demanding greater attention to our own definitions of health-related quality of life, including a satisfactory sex life.3
In fact, some of this increase in STIs among older Americans could be explained by the availability of treatments that address the sexual dysfunction that comes with aging. Previous generations of older adults have faced menopause and erectile dysfunction—but Baby Boomers are living and aging at a time when the symptoms can be more effectively managed. For older women, there are bioidentical hormones to replace those lost during menopause, which is often cited as the primary offender affecting their sexual lives (despite research suggesting that social and psychologic factors—emotional well-being, a strong emotional association with one’s partner, and positive body image—may be more foretelling of sexual activity later in life than the hormonal changes related to menopause).4
As for erectile dysfunction, yes, some men still feel awkward about bringing it up with their clinician; it can feel enfeebling for men to acknowledge, even though the physiologic changes are explained by the biology of aging (as we alluded to last week). Continuing sales of Viagra and Cialis suggest that boomer men are overcoming the stigmas of revealing their erectile dysfunction, however.
And maybe that is a contributing factor to this trend in STIs: We are being equipped for sexual performance, but perhaps we haven’t been adequately educated on what the consequences of our sexual encounters are. A lot of today’s seniors were already married when sex education gained prominence and perhaps missed the “safe sex” talks.
When I discussed this with a colleague of mine—a retired employee of the State Department—he noted that this topic was talked about even among US Embassy staff! At the risk of making a sweeping generalization and stating the obvious, he observed that “sexual mores have changed over time. Even many generations ago, they thought previous generations had been restrictive about sexual behavior!” Nevertheless, we agreed that the generation now emerging as “older Americans” grew up during the ’60s Free Love movement—and that philosophy seems to have carried into some individuals’ current sexual behavior. My colleague also noted that “as we get older, we lose partners—and sexual monogamy is lost with the loss of a partner.”
Continue to: The Baby Boomers...
The Baby Boomers are by far the most sexually liberal generation of older adults that this country has ever seen. Providing health care to this population requires addressing all health care needs, including sexual health and prevention. Next week, we’ll examine ways clinicians can comfortably broach these topics with older patients.
In the meantime, I’d love to hear your thoughts: Is this the Second Spring of the Summer of Love generation? Whether you’re a Boomer or a Millennial or anyone in between, feel free to write to me at [email protected].
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
1. Kickbusch I, Payne L. Twenty-first century health promotion: the public health revolution meets the wellness revolution. Health Promot Int. 2003;18(4):275-278.
2. Wilson LB, Simson SP (eds). Civic Engagement and the Baby Boomer Generation: Research, Policy, and Practice Perspectives. New York, NY: Haworth Press; 2006.
3. Kane RL, Kane RA. What older people want from long-term care, and how they can get it. Health Aff. 2001;20(6):114-127.
4. Bancroft J, Loftus J, Long JS. Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav. 2003;32(3):193-208.
FDA approves midazolam nasal spray for seizure clusters
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
The Food and Drug Administration has approved midazolam (Nayzilam) nasal spray for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity – seizure clusters or acute repetitive seizures – that are distinct from a patient’s usual seizure pattern. The treatment is approved for patients with epilepsy aged 12 years and older, according to a news release from UCB, the company that markets the drug.
Nayzilam is the first FDA-approved nasal option for treating seizure clusters, and the nasally administered formulation may allow for people other than healthcare professionals to administer the benzodiazepine in patients who are actively seizing when a seizure cluster occurs, according to the news release.
Nayzilam is designed as a single-use treatment that can be carried with a patient. The drug is a Schedule IV controlled substance.
Nayzilam’s efficacy was studied in a randomized, double-blind, placebo-controlled trial that enrolled patients with epilepsy who had intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern.
During an open-label phase, 292 patients in the absence of seizure received two 5-mg doses of Nayzilam 10 minutes apart. During the randomized, double-blind, placebo-controlled phase, 201 patients treated a single seizure cluster episode in an outpatient setting with Nayzilam (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam between 10 minutes and 6 hours after the initial blinded dose of study drug.
Compared with patients who received placebo, significantly more patients who received Nayzilam had termination of seizures within 10 minutes after the initial blinded dose of study drug (80.6% vs. 70.1%) and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug (58.2% vs. 37.3%). Adverse reactions that occurred in 5% or more of patients who received Nayzilam were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Respiratory depression was observed with the administration of Nayzilam during clinical trials. Cardiac or respiratory arrest have occurred after administration of midazolam, and midazolam is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Nayzilam is contraindicated in patients with acute narrow-angle glaucoma. In addition, concomitant use of opioids, moderate or strong CYP3A4 inhibitors, or other CNS depressants entails risks. Antiepileptic drugs, including Nayzilam, increase the risk of suicidal thoughts or behavior, according to the announcement.
How an office theft can change your habits
Last week, my secretary was checking a patient out when I went into the little galley area across from her desk to get coffee. Unfortunately, I knocked the pot over and it broke, sending glass and hot coffee everywhere.
My secretary asked the patient to wait a minute, grabbed a roll of paper towels that was behind her, and ran over to help me clean up. She was with me for 1-2 minutes, then returned to finish signing the patient out while I picked up glass shards.
A while later, we realized that somewhere in that 2 minutes an envelope containing roughly $200 in copays had disappeared from her desk drawer. It had been there 30 minutes before when another patient had paid a copay in cash, and now it was gone.
My secretary? No. She’s been with me for more than 15 years. She’s never stolen from the practice before, so why would she start now? I trust her.
The only people who had access to the drawer in that time were the patient, her, and me. While the money was out of sight, it was within reach of anyone who leaned over the counter, opened the drawer to look through it, and grabbed it.
I admit I probably should have gone to the bank sooner. Normally, we only have $20-$40 in small bills on hand, which we use for change. Most people prefer credit cards. But in the 2-3 weeks before this, we had had an unusual number of people using cash for copays. Combined with a crazier schedule than usual, I just hadn’t had a chance to deposit the bills.
Obviously, I’m not going to do that again.
Generally, no one has a chance to reach over and grab the drawer, either. When a patient is checking out, my secretary is always there making the transaction. But this one time, we had an unexpected distraction and she left the desk to help me.
She’s not going to do that again with someone standing there, either.
$200 isn’t, even in a small practice, a make-or-break amount. It stings, but I’ll still be able to make payroll and pay the rent. At the end of the year, it will have to come out of my own salary, because that’s the nature of owning a business. I can’t (and wouldn’t) charge the next 200 patients a $1 “administrative fee” to cover it.
Of course, it’s possible I’m accusing the wrong person. But there wasn’t anyone in the office besides me, my secretary, and the patient in that time frame. I don’t have any actual proof, like a video, though, so I certainly can’t press charges. She didn’t schedule a follow-up visit, either, so doubt she’ll be coming back.
Why would a patient steal from a doctor who’s trying to help her? Money is the simple answer. She had an opportunity to look and take it, and she did. Her moral compass must be skewed toward dishonesty, and she took advantage of the situation. I doubt it was anything personal against me, or doctors, or the situation in general. She’s a thief, and in her mind, it was a business decision.
Of course, I could be wrong on that point. Maybe she did rationalize it by the incorrect, but widespread, belief that doctors are “rich.” In her mind, she may have thought I’d never notice it, therefore there’s nothing wrong with stealing from me.
Do I hold it against future patients? No. In 20 years this is the first time one has stolen anything of significant financial value from my office (we’ve lost pens, magazines, a stapler, and a snowman-shaped candy dish in the past). The vast majority of my patients are decent people who wouldn’t do something like this.
But it does cast a pall over new patients we don’t know. Next time I need help while someone’s being checked out, my secretary won’t be able to give it. Any amount over a few small bills for change will be promptly taken to the bank.
It’s a bitter pill that leaves a bad taste in my mouth. Not harmful in the grand scheme of things, but certainly unpleasant. My job is based on the idea that people trust me to do my best for them, and in return, I trust them to be honest with me in return.
But one morning last week, it was just a one-way street.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Last week, my secretary was checking a patient out when I went into the little galley area across from her desk to get coffee. Unfortunately, I knocked the pot over and it broke, sending glass and hot coffee everywhere.
My secretary asked the patient to wait a minute, grabbed a roll of paper towels that was behind her, and ran over to help me clean up. She was with me for 1-2 minutes, then returned to finish signing the patient out while I picked up glass shards.
A while later, we realized that somewhere in that 2 minutes an envelope containing roughly $200 in copays had disappeared from her desk drawer. It had been there 30 minutes before when another patient had paid a copay in cash, and now it was gone.
My secretary? No. She’s been with me for more than 15 years. She’s never stolen from the practice before, so why would she start now? I trust her.
The only people who had access to the drawer in that time were the patient, her, and me. While the money was out of sight, it was within reach of anyone who leaned over the counter, opened the drawer to look through it, and grabbed it.
I admit I probably should have gone to the bank sooner. Normally, we only have $20-$40 in small bills on hand, which we use for change. Most people prefer credit cards. But in the 2-3 weeks before this, we had had an unusual number of people using cash for copays. Combined with a crazier schedule than usual, I just hadn’t had a chance to deposit the bills.
Obviously, I’m not going to do that again.
Generally, no one has a chance to reach over and grab the drawer, either. When a patient is checking out, my secretary is always there making the transaction. But this one time, we had an unexpected distraction and she left the desk to help me.
She’s not going to do that again with someone standing there, either.
$200 isn’t, even in a small practice, a make-or-break amount. It stings, but I’ll still be able to make payroll and pay the rent. At the end of the year, it will have to come out of my own salary, because that’s the nature of owning a business. I can’t (and wouldn’t) charge the next 200 patients a $1 “administrative fee” to cover it.
Of course, it’s possible I’m accusing the wrong person. But there wasn’t anyone in the office besides me, my secretary, and the patient in that time frame. I don’t have any actual proof, like a video, though, so I certainly can’t press charges. She didn’t schedule a follow-up visit, either, so doubt she’ll be coming back.
Why would a patient steal from a doctor who’s trying to help her? Money is the simple answer. She had an opportunity to look and take it, and she did. Her moral compass must be skewed toward dishonesty, and she took advantage of the situation. I doubt it was anything personal against me, or doctors, or the situation in general. She’s a thief, and in her mind, it was a business decision.
Of course, I could be wrong on that point. Maybe she did rationalize it by the incorrect, but widespread, belief that doctors are “rich.” In her mind, she may have thought I’d never notice it, therefore there’s nothing wrong with stealing from me.
Do I hold it against future patients? No. In 20 years this is the first time one has stolen anything of significant financial value from my office (we’ve lost pens, magazines, a stapler, and a snowman-shaped candy dish in the past). The vast majority of my patients are decent people who wouldn’t do something like this.
But it does cast a pall over new patients we don’t know. Next time I need help while someone’s being checked out, my secretary won’t be able to give it. Any amount over a few small bills for change will be promptly taken to the bank.
It’s a bitter pill that leaves a bad taste in my mouth. Not harmful in the grand scheme of things, but certainly unpleasant. My job is based on the idea that people trust me to do my best for them, and in return, I trust them to be honest with me in return.
But one morning last week, it was just a one-way street.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Last week, my secretary was checking a patient out when I went into the little galley area across from her desk to get coffee. Unfortunately, I knocked the pot over and it broke, sending glass and hot coffee everywhere.
My secretary asked the patient to wait a minute, grabbed a roll of paper towels that was behind her, and ran over to help me clean up. She was with me for 1-2 minutes, then returned to finish signing the patient out while I picked up glass shards.
A while later, we realized that somewhere in that 2 minutes an envelope containing roughly $200 in copays had disappeared from her desk drawer. It had been there 30 minutes before when another patient had paid a copay in cash, and now it was gone.
My secretary? No. She’s been with me for more than 15 years. She’s never stolen from the practice before, so why would she start now? I trust her.
The only people who had access to the drawer in that time were the patient, her, and me. While the money was out of sight, it was within reach of anyone who leaned over the counter, opened the drawer to look through it, and grabbed it.
I admit I probably should have gone to the bank sooner. Normally, we only have $20-$40 in small bills on hand, which we use for change. Most people prefer credit cards. But in the 2-3 weeks before this, we had had an unusual number of people using cash for copays. Combined with a crazier schedule than usual, I just hadn’t had a chance to deposit the bills.
Obviously, I’m not going to do that again.
Generally, no one has a chance to reach over and grab the drawer, either. When a patient is checking out, my secretary is always there making the transaction. But this one time, we had an unexpected distraction and she left the desk to help me.
She’s not going to do that again with someone standing there, either.
$200 isn’t, even in a small practice, a make-or-break amount. It stings, but I’ll still be able to make payroll and pay the rent. At the end of the year, it will have to come out of my own salary, because that’s the nature of owning a business. I can’t (and wouldn’t) charge the next 200 patients a $1 “administrative fee” to cover it.
Of course, it’s possible I’m accusing the wrong person. But there wasn’t anyone in the office besides me, my secretary, and the patient in that time frame. I don’t have any actual proof, like a video, though, so I certainly can’t press charges. She didn’t schedule a follow-up visit, either, so doubt she’ll be coming back.
Why would a patient steal from a doctor who’s trying to help her? Money is the simple answer. She had an opportunity to look and take it, and she did. Her moral compass must be skewed toward dishonesty, and she took advantage of the situation. I doubt it was anything personal against me, or doctors, or the situation in general. She’s a thief, and in her mind, it was a business decision.
Of course, I could be wrong on that point. Maybe she did rationalize it by the incorrect, but widespread, belief that doctors are “rich.” In her mind, she may have thought I’d never notice it, therefore there’s nothing wrong with stealing from me.
Do I hold it against future patients? No. In 20 years this is the first time one has stolen anything of significant financial value from my office (we’ve lost pens, magazines, a stapler, and a snowman-shaped candy dish in the past). The vast majority of my patients are decent people who wouldn’t do something like this.
But it does cast a pall over new patients we don’t know. Next time I need help while someone’s being checked out, my secretary won’t be able to give it. Any amount over a few small bills for change will be promptly taken to the bank.
It’s a bitter pill that leaves a bad taste in my mouth. Not harmful in the grand scheme of things, but certainly unpleasant. My job is based on the idea that people trust me to do my best for them, and in return, I trust them to be honest with me in return.
But one morning last week, it was just a one-way street.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Belatacept may mitigate skin cancer risk in transplant patients
CHICAGO – Compared with that of calcineurin inhibitors, belatacept appears to be associated with a lower risk of keratinocyte carcinomas in solid organ transplant patients, based on results from a single-center analysis presented at the annual meeting of the Society for Investigative Dermatology.
“Belatacept may offer a better risk-benefit profile in regards to skin cancer,” reported Michael Wang, a medical student who conducted this research in collaboration with the senior author, Oscar Colegio, MD, PhD, an associate professor of dermatology, pathology, and surgery at Yale University, New Haven, Conn.
Belatacept, a CTLA-4 fusion protein, has been compared with calcineurin inhibitors in two previous studies. The results were equivocal in one, and the other found no difference in risk and could not rule out the possibility that skin cancer risk was even higher on belatacept.
This single-center chart review included 110 kidney transplant patients, median age 58 years, who were switched from a calcineurin inhibitor, such as cyclosporine or tacrolimus, to belatacept. Ultimately, the study was limited to the 66 patients with at least 2 years of dermatologic follow-up both before and after the switch from a calcineurin inhibitor.
The primary outcome was the number of keratinocyte carcinomas overall and, specifically, the number of squamous cell carcinomas (SCCs) before and after the switch. Over the course of this study there were 128 cutaneous malignancies, 83 of which were SCCs.
When patients were on a calcineurin inhibitor, the risk of keratinocyte carcinomas increased incrementally by 2.6 events per 100 patients per year of follow-up, and the risk of SCCs increased by 1.7 events per 100 patients per year of follow-up. In the first 6 months after the switch to belatacept, there was no change in the rising trajectory of skin cancers, but rates declined thereafter.
Relative to rates prior to and 6 months after the switch, “the incidence of SCCs decreased at a rate of 5.9 events per 100 patients per year (P = .0068), and the incidence of keratinocyte carcinomas decreased by 7.1 events per 100 patients per year (P = .003),” Mr. Wang reported. He noted, however, that the incidence of basal cell carcinomas and melanomas following the switch remained unchanged.
When patients switched to belatacept were compared with another group of patients who remained on a calcineurin inhibitor after developing a SCC, the hazard ratio for a new SCC was 0.42, indicating a greater than 50% reduction in risk.
In patients on calcineurin inhibitors, the risk of keratinocyte carcinomas appears to be related to a direct effect of these agents on keratinocyte dedifferentiation. Belatacept is not believed to have any direct effects on keratinocytes, according to Mr. Wang.
As the chart review was retrospective and limited to a single center, “we hope [the findings] will encourage a prospective trial,” Mr. Wang said.
SOURCE: Wang M. SID 2019, Abstract 532.
CHICAGO – Compared with that of calcineurin inhibitors, belatacept appears to be associated with a lower risk of keratinocyte carcinomas in solid organ transplant patients, based on results from a single-center analysis presented at the annual meeting of the Society for Investigative Dermatology.
“Belatacept may offer a better risk-benefit profile in regards to skin cancer,” reported Michael Wang, a medical student who conducted this research in collaboration with the senior author, Oscar Colegio, MD, PhD, an associate professor of dermatology, pathology, and surgery at Yale University, New Haven, Conn.
Belatacept, a CTLA-4 fusion protein, has been compared with calcineurin inhibitors in two previous studies. The results were equivocal in one, and the other found no difference in risk and could not rule out the possibility that skin cancer risk was even higher on belatacept.
This single-center chart review included 110 kidney transplant patients, median age 58 years, who were switched from a calcineurin inhibitor, such as cyclosporine or tacrolimus, to belatacept. Ultimately, the study was limited to the 66 patients with at least 2 years of dermatologic follow-up both before and after the switch from a calcineurin inhibitor.
The primary outcome was the number of keratinocyte carcinomas overall and, specifically, the number of squamous cell carcinomas (SCCs) before and after the switch. Over the course of this study there were 128 cutaneous malignancies, 83 of which were SCCs.
When patients were on a calcineurin inhibitor, the risk of keratinocyte carcinomas increased incrementally by 2.6 events per 100 patients per year of follow-up, and the risk of SCCs increased by 1.7 events per 100 patients per year of follow-up. In the first 6 months after the switch to belatacept, there was no change in the rising trajectory of skin cancers, but rates declined thereafter.
Relative to rates prior to and 6 months after the switch, “the incidence of SCCs decreased at a rate of 5.9 events per 100 patients per year (P = .0068), and the incidence of keratinocyte carcinomas decreased by 7.1 events per 100 patients per year (P = .003),” Mr. Wang reported. He noted, however, that the incidence of basal cell carcinomas and melanomas following the switch remained unchanged.
When patients switched to belatacept were compared with another group of patients who remained on a calcineurin inhibitor after developing a SCC, the hazard ratio for a new SCC was 0.42, indicating a greater than 50% reduction in risk.
In patients on calcineurin inhibitors, the risk of keratinocyte carcinomas appears to be related to a direct effect of these agents on keratinocyte dedifferentiation. Belatacept is not believed to have any direct effects on keratinocytes, according to Mr. Wang.
As the chart review was retrospective and limited to a single center, “we hope [the findings] will encourage a prospective trial,” Mr. Wang said.
SOURCE: Wang M. SID 2019, Abstract 532.
CHICAGO – Compared with that of calcineurin inhibitors, belatacept appears to be associated with a lower risk of keratinocyte carcinomas in solid organ transplant patients, based on results from a single-center analysis presented at the annual meeting of the Society for Investigative Dermatology.
“Belatacept may offer a better risk-benefit profile in regards to skin cancer,” reported Michael Wang, a medical student who conducted this research in collaboration with the senior author, Oscar Colegio, MD, PhD, an associate professor of dermatology, pathology, and surgery at Yale University, New Haven, Conn.
Belatacept, a CTLA-4 fusion protein, has been compared with calcineurin inhibitors in two previous studies. The results were equivocal in one, and the other found no difference in risk and could not rule out the possibility that skin cancer risk was even higher on belatacept.
This single-center chart review included 110 kidney transplant patients, median age 58 years, who were switched from a calcineurin inhibitor, such as cyclosporine or tacrolimus, to belatacept. Ultimately, the study was limited to the 66 patients with at least 2 years of dermatologic follow-up both before and after the switch from a calcineurin inhibitor.
The primary outcome was the number of keratinocyte carcinomas overall and, specifically, the number of squamous cell carcinomas (SCCs) before and after the switch. Over the course of this study there were 128 cutaneous malignancies, 83 of which were SCCs.
When patients were on a calcineurin inhibitor, the risk of keratinocyte carcinomas increased incrementally by 2.6 events per 100 patients per year of follow-up, and the risk of SCCs increased by 1.7 events per 100 patients per year of follow-up. In the first 6 months after the switch to belatacept, there was no change in the rising trajectory of skin cancers, but rates declined thereafter.
Relative to rates prior to and 6 months after the switch, “the incidence of SCCs decreased at a rate of 5.9 events per 100 patients per year (P = .0068), and the incidence of keratinocyte carcinomas decreased by 7.1 events per 100 patients per year (P = .003),” Mr. Wang reported. He noted, however, that the incidence of basal cell carcinomas and melanomas following the switch remained unchanged.
When patients switched to belatacept were compared with another group of patients who remained on a calcineurin inhibitor after developing a SCC, the hazard ratio for a new SCC was 0.42, indicating a greater than 50% reduction in risk.
In patients on calcineurin inhibitors, the risk of keratinocyte carcinomas appears to be related to a direct effect of these agents on keratinocyte dedifferentiation. Belatacept is not believed to have any direct effects on keratinocytes, according to Mr. Wang.
As the chart review was retrospective and limited to a single center, “we hope [the findings] will encourage a prospective trial,” Mr. Wang said.
SOURCE: Wang M. SID 2019, Abstract 532.
REPORTING FROM SID 2019
Graham-Little-Piccardi-Lassueur Syndrome
To the Editor:
A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).
Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,2 and the inverse also has been reported.1 The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.
This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.3 More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.4 All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.6 Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.
The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.7
The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.8 Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.9 Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.9 Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.10
As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.11 The GLPL variant of LPP is reported up to 4 times more frequently in females.5 Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.12 Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.13 Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.14 Our patient had no relevant family history.
Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.2 Additional workup for viral triggers also has been negative.15 A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.16 There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.10,17 A case-control study by Mesinkovska et al17 revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,4 and a case of GLPL following hepatitis B vaccination also has been described.18
Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.13 Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.19
Histologically, cicatricial alopecia of the scalp is characterized by an interface dermatitis and a lichenoid lymphocytic infiltrate of the isthmus and infundibulum of the hair follicle sparing the bulb (Figure). A follicular plug is present in the active border. The increased pressure from the keratinous plug from above and the pressure from the infiltrate from the sides has been proposed to decrease the blood supply to the follicle and result in its death.2 Late-stage disease is notable for fibrotic longitudinal tracks of the hair follicle, perifollicular lamellar fibrosis, and adjacent epidermal atrophy.20 Direct immunofluorescence in GLPL generally is negative. A trichogram performed in a 29-year-old woman with GLPL was normal, with 84% anagen, 2% catagen, and 14% telogen hairs. It was noted that 10% of the sampled hairs were classified as dystrophical dysplastic hairs.12 Despite the lack of fibrosis on physical examination in patients with GLPL, nonscarring alopecia of the axilla and groin may show follicular destruction on microscopic examination.1 The pathology of the papules present on the trunk and extremities—whether that of keratosis pilaris or lichen spinulosus—demonstrates similar hyperkeratosis, hypergranulosis, and follicular plugging with a possible superficial, perivascular, lymphocytic infiltrate.
The differential diagnosis of GLPL includes other variants of LPP as well as discoid lupus erythematous (DLE), pseudopelade of Brocq, pityriasis rubra pilaris, sarcoidosis, acne keloidalis, central centrifugal scarring alopecia, follicular mucinosis, and folliculitis decalvans.14 Differentiation of LPP from DLE is difficult. Clinical clues include lack of central erythema and telangiectases within the lesions. Histologically, the lymphocytic dermatitis and folliculitis can be indistinguishable, but subtle findings suggesting DLE may be present, such as increased mucin in the reticular dermis, a focally thinned epidermis, and less severe dermal sclerosis when compared to cases of LPP.2 Direct immunofluorescence with IgG and C3 revealing linear granular deposits at the dermoepidermal junction is characteristic of DLE.20 Pseudopelade of Brocq is best thought of as an end-stage clinical pattern of hair loss in LPP rather than a separate condition. It is considered to be the end point of GLPL as well as DLE and others when the inflammation has subsided and the cicatricial alopecia is stable. For the duration of active disease, GLPL is classified as an unstable cicatricial alopecia that has a tendency to progress and recur periodically.20 Folliculitis decalvans also can mimic GLPL during a period when the pustules have resolved; however, a neutrophilic infiltrate will be present.
The goal of treatment in GLPL as well as other scarring alopecias is to stop the progression of hair loss. Early diagnosis is imperative if control is to be gained before considerable hair loss has occurred. Once follicular destruction has occurred as a result of the inflammation, there is minimal potential for hair rejuvenation.21 To date, treatment has been mostly fruitless, except in the management of keratosis pilaris that accompanies GLPL. First-line therapy often includes topical corticosteroids with or without intralesional corticosteroids. Systemic corticosteroids, retinoids, and psoralen plus UVA therapy also are frequently employed.1,2 Success in treating GLPL with cyclosporine A at a dosage of 4 mg/kg daily was described in several studies.1,2,15 Treatment resulted in reduction of perifollicular erythema and follicular hyperkeratotic papules as well as mild hair regrowth within the scarring patches.15 Nonetheless, cyclosporine A may prove useful in the initial inflammatory phase of GLPL. Consequently, cyclosporine A also is associated with a high relapse rate.1,2
Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.24 Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.25 Antimalarial medications also have been implemented as adjunct therapies with mixed results.5 A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.7 Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.6 Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.10 Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,26 but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.27
Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.28 Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.28 Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.
Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.
- Zegarska B, Kallas D, Schwartz RA, et al. Graham-Little syndrome. Acta Dermatovenerol Alp Pannonica Adriat. 2010;19:39-42.
- Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg. 2009;28:3-10.
- Olsen EA, Bergfield WF, Cotsarelis G, et al. Summary of North American Hair Research Society (NAHRS)–sponsored Workshop on Cicatricial Alopecia, Duke University Medical Center, February 10 and 11, 2001. J Am Acad Dermatol. 2003;48:103-110.
- Zinkernagel MS, Trueb RM. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol. 2000;136:205-211.
- James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: WB Saunders Company; 2016.
- Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. J Am Acad Dermatol. 1997;36:59-66.
- Pai VV, Kikkeri NN, Sori T, et al. Graham-Little Piccardi Lassueur syndrome: an unusual variant of follicular lichen planus. Int J Trichology. 2011;3:28-30.
- Srivastava M, Mikkilineni R, Konstadt J. Lassueur-Graham-Little-Piccardi syndrome. Dermatol Online J. 2007;13:12.
- Brar BK, Khanna E, Mahajan BB. Graham Little Piccardi Lasseur syndrome: a rare case report with concomitant hypertrophic lichen planus. Int J Trichology. 2011;5:199-200.
- Vashi N, Newlove T, Chu J, et al. Graham-Little-Piccardi-Lassueur syndrome. Dermatol Online J. 2011;17:30.
- Chieregato C, Zini A, Barba A, et al. Lichen planopilaris: report of 30 cases and review of the literature. Int J Dermatol. 2003;42:342-345.
- Vega Gutierrez J, Miranda-Romera A, Perez Milan F, et al. Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization). J Eur Acad Dermatol Venereol. 2004;18:463-466.
- Rodríguez-Bayona B, Ruchaud S, Rodriguez C, et al. Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome. J Autoimmune Dis. 2007;4:1.
- Viglizzo G, Verrini A, Rongioletti F. Familial Lassueur-Graham-Little-Piccardi syndrome. Dermatology. 2004;208:142-144.
- Bianchi L, Paro Vidolin A, Piemonte P, et al. Graham Little-Piccardi-Lassueur syndrome: effective treatment with cyclosporin A. Clin Exp Dermatol. 2001;26:518-520.
- Cevasco NC, Bergfeld WF, Remzi BK, et al. A case-series of 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. J Am Acad Dermatol. 2007;57:47-53.
- Mesinkovska NA, Brankov N, Piliang M, et al. Association of lichen planopilaris with thyroid disease: a retrospective case-control study. J Am Acad Dermatol. 2014;70:889-892.
- Bardazzi F, Landi C, Orlandi C, et al. Graham Little-Piccardi-Lasseur syndrome following HBV vaccination. Acta Derm Venereol. 1999;79:93.
- Hutchens KA, Balfour EM, Smoller BR. Comparison between Langerhans cell concentration in lichen planopilaris and traction alopecia with possible immunologic implications. Am J Dermatopathol. 2011;33:277-280.
- Dogra S, Sarangal R. What’s new in cicatricial alopecia? Indian J Dermatol Venereol Leprol. 2013;79:576-590.
- Daoud MS, Pittelkow MR. Lichen planus. In: Wolff K, Goldsmith LA, Katz Si, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: Mc Graw Hill; 2008:463-477.
- Donati A, Assouly P, Matard B, et al. Clinical and photographic assessment of lichen planopilaris treatment efficacy. J Am Acad Dermatol. 2011;64:597-599.
- Samrao A, Chew AL, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.
- Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;145:333-334.
- Ladizinski B, Bazakas A, Selim MA, et al. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol. 2013;68:749-755
- George SJ, Hsu SJ. Lichen planopilaris treated with thalidomide. J Am Acad Dermatol. 2001;45:965-966.
- Jouanique C, Reygagne P, Bachelez H, et al. Thalidomide is ineffective in the treatment of lichen planopilaris. J Am Acad Dermatol. 2004;51:480-481.
- Mirmirani P, Karnik P. Lichen planopilaris treated with a peroxisome proliferator–activated receptor γ agonist. Arch Dermatol. 2009;145:1363-1366.
To the Editor:
A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).
Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,2 and the inverse also has been reported.1 The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.
This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.3 More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.4 All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.6 Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.
The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.7
The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.8 Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.9 Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.9 Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.10
As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.11 The GLPL variant of LPP is reported up to 4 times more frequently in females.5 Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.12 Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.13 Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.14 Our patient had no relevant family history.
Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.2 Additional workup for viral triggers also has been negative.15 A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.16 There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.10,17 A case-control study by Mesinkovska et al17 revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,4 and a case of GLPL following hepatitis B vaccination also has been described.18
Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.13 Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.19
Histologically, cicatricial alopecia of the scalp is characterized by an interface dermatitis and a lichenoid lymphocytic infiltrate of the isthmus and infundibulum of the hair follicle sparing the bulb (Figure). A follicular plug is present in the active border. The increased pressure from the keratinous plug from above and the pressure from the infiltrate from the sides has been proposed to decrease the blood supply to the follicle and result in its death.2 Late-stage disease is notable for fibrotic longitudinal tracks of the hair follicle, perifollicular lamellar fibrosis, and adjacent epidermal atrophy.20 Direct immunofluorescence in GLPL generally is negative. A trichogram performed in a 29-year-old woman with GLPL was normal, with 84% anagen, 2% catagen, and 14% telogen hairs. It was noted that 10% of the sampled hairs were classified as dystrophical dysplastic hairs.12 Despite the lack of fibrosis on physical examination in patients with GLPL, nonscarring alopecia of the axilla and groin may show follicular destruction on microscopic examination.1 The pathology of the papules present on the trunk and extremities—whether that of keratosis pilaris or lichen spinulosus—demonstrates similar hyperkeratosis, hypergranulosis, and follicular plugging with a possible superficial, perivascular, lymphocytic infiltrate.
The differential diagnosis of GLPL includes other variants of LPP as well as discoid lupus erythematous (DLE), pseudopelade of Brocq, pityriasis rubra pilaris, sarcoidosis, acne keloidalis, central centrifugal scarring alopecia, follicular mucinosis, and folliculitis decalvans.14 Differentiation of LPP from DLE is difficult. Clinical clues include lack of central erythema and telangiectases within the lesions. Histologically, the lymphocytic dermatitis and folliculitis can be indistinguishable, but subtle findings suggesting DLE may be present, such as increased mucin in the reticular dermis, a focally thinned epidermis, and less severe dermal sclerosis when compared to cases of LPP.2 Direct immunofluorescence with IgG and C3 revealing linear granular deposits at the dermoepidermal junction is characteristic of DLE.20 Pseudopelade of Brocq is best thought of as an end-stage clinical pattern of hair loss in LPP rather than a separate condition. It is considered to be the end point of GLPL as well as DLE and others when the inflammation has subsided and the cicatricial alopecia is stable. For the duration of active disease, GLPL is classified as an unstable cicatricial alopecia that has a tendency to progress and recur periodically.20 Folliculitis decalvans also can mimic GLPL during a period when the pustules have resolved; however, a neutrophilic infiltrate will be present.
The goal of treatment in GLPL as well as other scarring alopecias is to stop the progression of hair loss. Early diagnosis is imperative if control is to be gained before considerable hair loss has occurred. Once follicular destruction has occurred as a result of the inflammation, there is minimal potential for hair rejuvenation.21 To date, treatment has been mostly fruitless, except in the management of keratosis pilaris that accompanies GLPL. First-line therapy often includes topical corticosteroids with or without intralesional corticosteroids. Systemic corticosteroids, retinoids, and psoralen plus UVA therapy also are frequently employed.1,2 Success in treating GLPL with cyclosporine A at a dosage of 4 mg/kg daily was described in several studies.1,2,15 Treatment resulted in reduction of perifollicular erythema and follicular hyperkeratotic papules as well as mild hair regrowth within the scarring patches.15 Nonetheless, cyclosporine A may prove useful in the initial inflammatory phase of GLPL. Consequently, cyclosporine A also is associated with a high relapse rate.1,2
Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.24 Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.25 Antimalarial medications also have been implemented as adjunct therapies with mixed results.5 A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.7 Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.6 Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.10 Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,26 but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.27
Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.28 Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.28 Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.
Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.
To the Editor:
A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).
Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,2 and the inverse also has been reported.1 The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.
This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.3 More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.4 All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.6 Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.
The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.7
The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.8 Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.9 Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.9 Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.10
As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.11 The GLPL variant of LPP is reported up to 4 times more frequently in females.5 Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.12 Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.13 Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.14 Our patient had no relevant family history.
Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.2 Additional workup for viral triggers also has been negative.15 A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.16 There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.10,17 A case-control study by Mesinkovska et al17 revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,4 and a case of GLPL following hepatitis B vaccination also has been described.18
Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.13 Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.19
Histologically, cicatricial alopecia of the scalp is characterized by an interface dermatitis and a lichenoid lymphocytic infiltrate of the isthmus and infundibulum of the hair follicle sparing the bulb (Figure). A follicular plug is present in the active border. The increased pressure from the keratinous plug from above and the pressure from the infiltrate from the sides has been proposed to decrease the blood supply to the follicle and result in its death.2 Late-stage disease is notable for fibrotic longitudinal tracks of the hair follicle, perifollicular lamellar fibrosis, and adjacent epidermal atrophy.20 Direct immunofluorescence in GLPL generally is negative. A trichogram performed in a 29-year-old woman with GLPL was normal, with 84% anagen, 2% catagen, and 14% telogen hairs. It was noted that 10% of the sampled hairs were classified as dystrophical dysplastic hairs.12 Despite the lack of fibrosis on physical examination in patients with GLPL, nonscarring alopecia of the axilla and groin may show follicular destruction on microscopic examination.1 The pathology of the papules present on the trunk and extremities—whether that of keratosis pilaris or lichen spinulosus—demonstrates similar hyperkeratosis, hypergranulosis, and follicular plugging with a possible superficial, perivascular, lymphocytic infiltrate.
The differential diagnosis of GLPL includes other variants of LPP as well as discoid lupus erythematous (DLE), pseudopelade of Brocq, pityriasis rubra pilaris, sarcoidosis, acne keloidalis, central centrifugal scarring alopecia, follicular mucinosis, and folliculitis decalvans.14 Differentiation of LPP from DLE is difficult. Clinical clues include lack of central erythema and telangiectases within the lesions. Histologically, the lymphocytic dermatitis and folliculitis can be indistinguishable, but subtle findings suggesting DLE may be present, such as increased mucin in the reticular dermis, a focally thinned epidermis, and less severe dermal sclerosis when compared to cases of LPP.2 Direct immunofluorescence with IgG and C3 revealing linear granular deposits at the dermoepidermal junction is characteristic of DLE.20 Pseudopelade of Brocq is best thought of as an end-stage clinical pattern of hair loss in LPP rather than a separate condition. It is considered to be the end point of GLPL as well as DLE and others when the inflammation has subsided and the cicatricial alopecia is stable. For the duration of active disease, GLPL is classified as an unstable cicatricial alopecia that has a tendency to progress and recur periodically.20 Folliculitis decalvans also can mimic GLPL during a period when the pustules have resolved; however, a neutrophilic infiltrate will be present.
The goal of treatment in GLPL as well as other scarring alopecias is to stop the progression of hair loss. Early diagnosis is imperative if control is to be gained before considerable hair loss has occurred. Once follicular destruction has occurred as a result of the inflammation, there is minimal potential for hair rejuvenation.21 To date, treatment has been mostly fruitless, except in the management of keratosis pilaris that accompanies GLPL. First-line therapy often includes topical corticosteroids with or without intralesional corticosteroids. Systemic corticosteroids, retinoids, and psoralen plus UVA therapy also are frequently employed.1,2 Success in treating GLPL with cyclosporine A at a dosage of 4 mg/kg daily was described in several studies.1,2,15 Treatment resulted in reduction of perifollicular erythema and follicular hyperkeratotic papules as well as mild hair regrowth within the scarring patches.15 Nonetheless, cyclosporine A may prove useful in the initial inflammatory phase of GLPL. Consequently, cyclosporine A also is associated with a high relapse rate.1,2
Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.24 Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.25 Antimalarial medications also have been implemented as adjunct therapies with mixed results.5 A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.7 Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.6 Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.10 Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,26 but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.27
Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.28 Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.28 Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.
Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.
- Zegarska B, Kallas D, Schwartz RA, et al. Graham-Little syndrome. Acta Dermatovenerol Alp Pannonica Adriat. 2010;19:39-42.
- Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg. 2009;28:3-10.
- Olsen EA, Bergfield WF, Cotsarelis G, et al. Summary of North American Hair Research Society (NAHRS)–sponsored Workshop on Cicatricial Alopecia, Duke University Medical Center, February 10 and 11, 2001. J Am Acad Dermatol. 2003;48:103-110.
- Zinkernagel MS, Trueb RM. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol. 2000;136:205-211.
- James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: WB Saunders Company; 2016.
- Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. J Am Acad Dermatol. 1997;36:59-66.
- Pai VV, Kikkeri NN, Sori T, et al. Graham-Little Piccardi Lassueur syndrome: an unusual variant of follicular lichen planus. Int J Trichology. 2011;3:28-30.
- Srivastava M, Mikkilineni R, Konstadt J. Lassueur-Graham-Little-Piccardi syndrome. Dermatol Online J. 2007;13:12.
- Brar BK, Khanna E, Mahajan BB. Graham Little Piccardi Lasseur syndrome: a rare case report with concomitant hypertrophic lichen planus. Int J Trichology. 2011;5:199-200.
- Vashi N, Newlove T, Chu J, et al. Graham-Little-Piccardi-Lassueur syndrome. Dermatol Online J. 2011;17:30.
- Chieregato C, Zini A, Barba A, et al. Lichen planopilaris: report of 30 cases and review of the literature. Int J Dermatol. 2003;42:342-345.
- Vega Gutierrez J, Miranda-Romera A, Perez Milan F, et al. Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization). J Eur Acad Dermatol Venereol. 2004;18:463-466.
- Rodríguez-Bayona B, Ruchaud S, Rodriguez C, et al. Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome. J Autoimmune Dis. 2007;4:1.
- Viglizzo G, Verrini A, Rongioletti F. Familial Lassueur-Graham-Little-Piccardi syndrome. Dermatology. 2004;208:142-144.
- Bianchi L, Paro Vidolin A, Piemonte P, et al. Graham Little-Piccardi-Lassueur syndrome: effective treatment with cyclosporin A. Clin Exp Dermatol. 2001;26:518-520.
- Cevasco NC, Bergfeld WF, Remzi BK, et al. A case-series of 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. J Am Acad Dermatol. 2007;57:47-53.
- Mesinkovska NA, Brankov N, Piliang M, et al. Association of lichen planopilaris with thyroid disease: a retrospective case-control study. J Am Acad Dermatol. 2014;70:889-892.
- Bardazzi F, Landi C, Orlandi C, et al. Graham Little-Piccardi-Lasseur syndrome following HBV vaccination. Acta Derm Venereol. 1999;79:93.
- Hutchens KA, Balfour EM, Smoller BR. Comparison between Langerhans cell concentration in lichen planopilaris and traction alopecia with possible immunologic implications. Am J Dermatopathol. 2011;33:277-280.
- Dogra S, Sarangal R. What’s new in cicatricial alopecia? Indian J Dermatol Venereol Leprol. 2013;79:576-590.
- Daoud MS, Pittelkow MR. Lichen planus. In: Wolff K, Goldsmith LA, Katz Si, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: Mc Graw Hill; 2008:463-477.
- Donati A, Assouly P, Matard B, et al. Clinical and photographic assessment of lichen planopilaris treatment efficacy. J Am Acad Dermatol. 2011;64:597-599.
- Samrao A, Chew AL, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.
- Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;145:333-334.
- Ladizinski B, Bazakas A, Selim MA, et al. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol. 2013;68:749-755
- George SJ, Hsu SJ. Lichen planopilaris treated with thalidomide. J Am Acad Dermatol. 2001;45:965-966.
- Jouanique C, Reygagne P, Bachelez H, et al. Thalidomide is ineffective in the treatment of lichen planopilaris. J Am Acad Dermatol. 2004;51:480-481.
- Mirmirani P, Karnik P. Lichen planopilaris treated with a peroxisome proliferator–activated receptor γ agonist. Arch Dermatol. 2009;145:1363-1366.
- Zegarska B, Kallas D, Schwartz RA, et al. Graham-Little syndrome. Acta Dermatovenerol Alp Pannonica Adriat. 2010;19:39-42.
- Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg. 2009;28:3-10.
- Olsen EA, Bergfield WF, Cotsarelis G, et al. Summary of North American Hair Research Society (NAHRS)–sponsored Workshop on Cicatricial Alopecia, Duke University Medical Center, February 10 and 11, 2001. J Am Acad Dermatol. 2003;48:103-110.
- Zinkernagel MS, Trueb RM. Fibrosing alopecia in a pattern distribution: patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol. 2000;136:205-211.
- James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: WB Saunders Company; 2016.
- Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris. J Am Acad Dermatol. 1997;36:59-66.
- Pai VV, Kikkeri NN, Sori T, et al. Graham-Little Piccardi Lassueur syndrome: an unusual variant of follicular lichen planus. Int J Trichology. 2011;3:28-30.
- Srivastava M, Mikkilineni R, Konstadt J. Lassueur-Graham-Little-Piccardi syndrome. Dermatol Online J. 2007;13:12.
- Brar BK, Khanna E, Mahajan BB. Graham Little Piccardi Lasseur syndrome: a rare case report with concomitant hypertrophic lichen planus. Int J Trichology. 2011;5:199-200.
- Vashi N, Newlove T, Chu J, et al. Graham-Little-Piccardi-Lassueur syndrome. Dermatol Online J. 2011;17:30.
- Chieregato C, Zini A, Barba A, et al. Lichen planopilaris: report of 30 cases and review of the literature. Int J Dermatol. 2003;42:342-345.
- Vega Gutierrez J, Miranda-Romera A, Perez Milan F, et al. Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization). J Eur Acad Dermatol Venereol. 2004;18:463-466.
- Rodríguez-Bayona B, Ruchaud S, Rodriguez C, et al. Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome. J Autoimmune Dis. 2007;4:1.
- Viglizzo G, Verrini A, Rongioletti F. Familial Lassueur-Graham-Little-Piccardi syndrome. Dermatology. 2004;208:142-144.
- Bianchi L, Paro Vidolin A, Piemonte P, et al. Graham Little-Piccardi-Lassueur syndrome: effective treatment with cyclosporin A. Clin Exp Dermatol. 2001;26:518-520.
- Cevasco NC, Bergfeld WF, Remzi BK, et al. A case-series of 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. J Am Acad Dermatol. 2007;57:47-53.
- Mesinkovska NA, Brankov N, Piliang M, et al. Association of lichen planopilaris with thyroid disease: a retrospective case-control study. J Am Acad Dermatol. 2014;70:889-892.
- Bardazzi F, Landi C, Orlandi C, et al. Graham Little-Piccardi-Lasseur syndrome following HBV vaccination. Acta Derm Venereol. 1999;79:93.
- Hutchens KA, Balfour EM, Smoller BR. Comparison between Langerhans cell concentration in lichen planopilaris and traction alopecia with possible immunologic implications. Am J Dermatopathol. 2011;33:277-280.
- Dogra S, Sarangal R. What’s new in cicatricial alopecia? Indian J Dermatol Venereol Leprol. 2013;79:576-590.
- Daoud MS, Pittelkow MR. Lichen planus. In: Wolff K, Goldsmith LA, Katz Si, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: Mc Graw Hill; 2008:463-477.
- Donati A, Assouly P, Matard B, et al. Clinical and photographic assessment of lichen planopilaris treatment efficacy. J Am Acad Dermatol. 2011;64:597-599.
- Samrao A, Chew AL, Price V. Frontal fibrosing alopecia: a clinical review of 36 patients. Br J Dermatol. 2010;163:1296-1300.
- Spencer LA, Hawryluk EB, English JC. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol. 2009;145:333-334.
- Ladizinski B, Bazakas A, Selim MA, et al. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol. 2013;68:749-755
- George SJ, Hsu SJ. Lichen planopilaris treated with thalidomide. J Am Acad Dermatol. 2001;45:965-966.
- Jouanique C, Reygagne P, Bachelez H, et al. Thalidomide is ineffective in the treatment of lichen planopilaris. J Am Acad Dermatol. 2004;51:480-481.
- Mirmirani P, Karnik P. Lichen planopilaris treated with a peroxisome proliferator–activated receptor γ agonist. Arch Dermatol. 2009;145:1363-1366.
Practice Points
- Graham-Little-Piccardi-Lassueur syndrome (GLPL) is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp.
- Graham-Little-Piccardi-Lassueur syndrome is considered one of the 3 clinical variants of lichen planopilaris.
- Potential therapies for GLPL include hydroxychloroquine, cyclosporine, tetracyclines, and pioglitazone.
Bariatric surgery found to be effective in IBD patients
SAN DIEGO – In carefully selected patients with well-controlled inflammatory bowel disease (IBD), bariatric surgery results in sustained weight loss over a 2-year period, results from a retrospective study suggest.
“Obesity is increasing in patients with inflammatory bowel disease at a rate similar to that seen in the general population,” the study’s primary author, Nicholas P. McKenna, MD, said in an interview in advance of the annual Digestive Disease Week. “While bariatric surgery is a well-accepted therapy for obesity in patients without IBD, its use in patients with IBD is less well studied.”
For the current study, Dr. McKenna, a resident in the department of surgery at the Mayo Clinic in Rochester, Minn., and colleagues collected data on 33 patients who underwent bariatric surgery with a pre- or postoperative diagnosis of IBD across three academic centers between August 2006 and December 2017. They evaluated IBD characteristics and medications; postoperative complications; the need for future IBD-related surgery; and weight loss at 6, 12, and 24 months.
The patients underwent 34 bariatric operations. Their median age was 51 years and their median duration of IBD was 13 years. Of the 33 patients, 16 underwent a Roux-en-Y gastric bypass procedure: 9 who had ulcerative colitis, 6 who had Crohn’s disease, and 1 who had indeterminate colitis. A total of 14 patients underwent sleeve gastrectomy: 7 who had ulcerative colitis and 7 who had Crohn’s disease. Four patients underwent a gastric band procedure, all of whom had ulcerative colitis. The mean body mass index of patients prior to their bariatric procedures was 42.7 kg/m2. A total of 31 patients had an existing diagnosis of IBD, and 2 were diagnosed with Crohn’s disease after Roux-en-Y gastric bypass. In addition, 9 patients were on preoperative immunosuppression for IBD, and 11 had undergone prior intestinal resection for IBD.
Dr. McKenna reported that the average hospitalization for all patients was 3.6 days and that only four 30-day infectious complications occurred: two superficial surgical site infections, one infected intra-abdominal hematoma, and one hepatic abscess. In the long term, seven patients required reoperation: three for failed gastric band, two for reduction of internal hernia, and two for cholelithiasis. The researchers found that the mean percentage of overall excess weight loss was 57.5% at 6 months, 63.3% at 12 months, and 58.6% at 24 months. During a mean follow-up of 3.4 years, no IBD flares requiring surgery were observed.
“Our hypothesis based on the existing literature was that bariatric surgery would be safe in carefully selected patients with IBD and result in sustained weight loss, so we were not surprised with these results,” Dr. McKenna said. “We were not sure if medication requirements would change after surgery as the literature is conflicted on this. We observed that most patients continued to require no immunosuppression for control of their IBD after surgery. Further, we did not observe that any patients required future surgery at the time of last follow-up for an IBD flare.”
He acknowledged certain limitations of the study, including its retrospective design. “Additionally, though it is a relatively large sample, compared to the existing literature on bariatric surgery in IBD, it is still only 33 patients. This limits the comparisons that can be performed between patients with ulcerative colitis and Crohn’s disease and between the operation choices.”
The study’s secondary author, Alaa Sada, MD, a surgery resident at Mayo, presented the findings at the meeting. The researchers reported having no financial disclosures.
SAN DIEGO – In carefully selected patients with well-controlled inflammatory bowel disease (IBD), bariatric surgery results in sustained weight loss over a 2-year period, results from a retrospective study suggest.
“Obesity is increasing in patients with inflammatory bowel disease at a rate similar to that seen in the general population,” the study’s primary author, Nicholas P. McKenna, MD, said in an interview in advance of the annual Digestive Disease Week. “While bariatric surgery is a well-accepted therapy for obesity in patients without IBD, its use in patients with IBD is less well studied.”
For the current study, Dr. McKenna, a resident in the department of surgery at the Mayo Clinic in Rochester, Minn., and colleagues collected data on 33 patients who underwent bariatric surgery with a pre- or postoperative diagnosis of IBD across three academic centers between August 2006 and December 2017. They evaluated IBD characteristics and medications; postoperative complications; the need for future IBD-related surgery; and weight loss at 6, 12, and 24 months.
The patients underwent 34 bariatric operations. Their median age was 51 years and their median duration of IBD was 13 years. Of the 33 patients, 16 underwent a Roux-en-Y gastric bypass procedure: 9 who had ulcerative colitis, 6 who had Crohn’s disease, and 1 who had indeterminate colitis. A total of 14 patients underwent sleeve gastrectomy: 7 who had ulcerative colitis and 7 who had Crohn’s disease. Four patients underwent a gastric band procedure, all of whom had ulcerative colitis. The mean body mass index of patients prior to their bariatric procedures was 42.7 kg/m2. A total of 31 patients had an existing diagnosis of IBD, and 2 were diagnosed with Crohn’s disease after Roux-en-Y gastric bypass. In addition, 9 patients were on preoperative immunosuppression for IBD, and 11 had undergone prior intestinal resection for IBD.
Dr. McKenna reported that the average hospitalization for all patients was 3.6 days and that only four 30-day infectious complications occurred: two superficial surgical site infections, one infected intra-abdominal hematoma, and one hepatic abscess. In the long term, seven patients required reoperation: three for failed gastric band, two for reduction of internal hernia, and two for cholelithiasis. The researchers found that the mean percentage of overall excess weight loss was 57.5% at 6 months, 63.3% at 12 months, and 58.6% at 24 months. During a mean follow-up of 3.4 years, no IBD flares requiring surgery were observed.
“Our hypothesis based on the existing literature was that bariatric surgery would be safe in carefully selected patients with IBD and result in sustained weight loss, so we were not surprised with these results,” Dr. McKenna said. “We were not sure if medication requirements would change after surgery as the literature is conflicted on this. We observed that most patients continued to require no immunosuppression for control of their IBD after surgery. Further, we did not observe that any patients required future surgery at the time of last follow-up for an IBD flare.”
He acknowledged certain limitations of the study, including its retrospective design. “Additionally, though it is a relatively large sample, compared to the existing literature on bariatric surgery in IBD, it is still only 33 patients. This limits the comparisons that can be performed between patients with ulcerative colitis and Crohn’s disease and between the operation choices.”
The study’s secondary author, Alaa Sada, MD, a surgery resident at Mayo, presented the findings at the meeting. The researchers reported having no financial disclosures.
SAN DIEGO – In carefully selected patients with well-controlled inflammatory bowel disease (IBD), bariatric surgery results in sustained weight loss over a 2-year period, results from a retrospective study suggest.
“Obesity is increasing in patients with inflammatory bowel disease at a rate similar to that seen in the general population,” the study’s primary author, Nicholas P. McKenna, MD, said in an interview in advance of the annual Digestive Disease Week. “While bariatric surgery is a well-accepted therapy for obesity in patients without IBD, its use in patients with IBD is less well studied.”
For the current study, Dr. McKenna, a resident in the department of surgery at the Mayo Clinic in Rochester, Minn., and colleagues collected data on 33 patients who underwent bariatric surgery with a pre- or postoperative diagnosis of IBD across three academic centers between August 2006 and December 2017. They evaluated IBD characteristics and medications; postoperative complications; the need for future IBD-related surgery; and weight loss at 6, 12, and 24 months.
The patients underwent 34 bariatric operations. Their median age was 51 years and their median duration of IBD was 13 years. Of the 33 patients, 16 underwent a Roux-en-Y gastric bypass procedure: 9 who had ulcerative colitis, 6 who had Crohn’s disease, and 1 who had indeterminate colitis. A total of 14 patients underwent sleeve gastrectomy: 7 who had ulcerative colitis and 7 who had Crohn’s disease. Four patients underwent a gastric band procedure, all of whom had ulcerative colitis. The mean body mass index of patients prior to their bariatric procedures was 42.7 kg/m2. A total of 31 patients had an existing diagnosis of IBD, and 2 were diagnosed with Crohn’s disease after Roux-en-Y gastric bypass. In addition, 9 patients were on preoperative immunosuppression for IBD, and 11 had undergone prior intestinal resection for IBD.
Dr. McKenna reported that the average hospitalization for all patients was 3.6 days and that only four 30-day infectious complications occurred: two superficial surgical site infections, one infected intra-abdominal hematoma, and one hepatic abscess. In the long term, seven patients required reoperation: three for failed gastric band, two for reduction of internal hernia, and two for cholelithiasis. The researchers found that the mean percentage of overall excess weight loss was 57.5% at 6 months, 63.3% at 12 months, and 58.6% at 24 months. During a mean follow-up of 3.4 years, no IBD flares requiring surgery were observed.
“Our hypothesis based on the existing literature was that bariatric surgery would be safe in carefully selected patients with IBD and result in sustained weight loss, so we were not surprised with these results,” Dr. McKenna said. “We were not sure if medication requirements would change after surgery as the literature is conflicted on this. We observed that most patients continued to require no immunosuppression for control of their IBD after surgery. Further, we did not observe that any patients required future surgery at the time of last follow-up for an IBD flare.”
He acknowledged certain limitations of the study, including its retrospective design. “Additionally, though it is a relatively large sample, compared to the existing literature on bariatric surgery in IBD, it is still only 33 patients. This limits the comparisons that can be performed between patients with ulcerative colitis and Crohn’s disease and between the operation choices.”
The study’s secondary author, Alaa Sada, MD, a surgery resident at Mayo, presented the findings at the meeting. The researchers reported having no financial disclosures.
REPORTING FROM DDW 2019
Chronic opioid use linked to low testosterone levels
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
REPORTING FROM ENDO 2019
