Mixed Topics

Average life expectancy fell in the United States fell from 78.7 years to 78.6 years from 2016 to 2017, according to a new report on the nation’s health. The decrease is primarily attributable to increases in suicide and drug overdose rates, according to new data from the Centers for Disease Control (CDC).

Darwin Brandis/gettyimages

“The latest CDC data show that the U.S. life expectancy has declined over the past few years. Tragically, this troubling trend is largely driven by deaths from drug overdose and suicide,” said CDC Director Robert Redfield, MD, in a statement.

Two subreports that looked specifically at suicide mortality and drug overdose deaths mapped out where, when, and for whom the sharpest increases in mortality are being seen.

For suicide, though rates have increased by 33% overall for both men and women since 1999, the greatest annual increases in suicide rates have happened since 2006, according to a new report from the CDC’s National Center for Health Statistics (NCHS).

Overall, suicide rates have climbed from 10.5 to 14.0 per 100,000 individuals, with statistically significant increases in suicide rates among all age groups except those aged 75 years and older.

Suicide rates rose more steeply in the most rural counties. The age-adjusted increase in the most rural counties was 53%, compared with an increase of 16% in suicide rates for the nation’s most urban counties over the 1999-2017 time period.

Over the entire period studied, men were more likely than women to experience suicide, as rates rose among most age groups. For example, the rates of suicide for men aged 15-24 years rose from 16.8 to 22.7 per 100,000; for women in that age group, suicide rates went from 3.0 to 5.8 per 100,000.

Though suicide has remained the 10th leading cause of death overall in the United States, suicide was the second leading cause of death for adolescents and young adults (aged 10-34) in 2016, and the fourth leading cause of death for those aged 35-54 in that year.

These increases come despite a goal set by the CDC and a national coalition of health partners to reduce suicide rates to 10.2 per 100,000 by 2020, as part of the Healthy People 2020 initiative, noted Molly Hedegaard, MD, of NCHS, and her coauthors, in the suicide mortality data briefing.

Drug overdoses increased by nearly 10% in one year, with the highest rates seen in adults aged 25-54 years, according to a second CDC data briefing.

The number of people who died of drug overdoses in the United States in 2017 was 70,237. This represents a year-over-year age-adjusted increase of 9.6%, from 19.8 to 21.7 per 100,000 individuals, said Dr. Hedegaard and the coauthors of the drug overdose mortality report.

Reflecting known national trends in opioid use disorder, age-adjusted drug overdose deaths were highest in the states of West Virginia, Ohio, and Pennsylvania, where rates were 57.8, 46.3, and 44.3 per 100,000 residents, respectively. The District of Columbia had the fourth-highest age adjusted drug overdose death rate, at 44 per 100,000.

Twenty states, clustered primarily in the Eastern half of the United States, “had age-adjusted drug overdose death rate that were statistically higher than the national rate,” wrote Dr. Hedegaard and her coauthors.

Compared with 1999, more than six times as many adults in older midlife (aged 55-64 years) died from drug overdoses in 2017 (4.2 versus 28 per 100,000).

Adults aged 25-34 years, 35-44 years, and 45-54 years also had significant increases in drug overdose rates; in 2017, rates were 38.4, 29, and 37.7 per 100,000, respectively. Adolescent and young adults died from drug overdoses at a rate of 12.6 per 100,000, and those over 65 years old had a death rate of 6.9 per 100,000.

Deaths attributable to synthetic opioid use, excluding methadone, rose by 45% in just one year, going from 6.2 to 9.0 per 100,000 nationally. In 1999, synthetic opioids other than methadone were implicated in just 0.3 per 100,000 deaths. Synthetic opioids include fentanyl and fentanyl analogs, such as carfentanyl.

Deaths involving heroin remained stable from 2016 to 2017, at 4.9 per 100,000. Deaths attributable to natural and semisynthetic prescription opioids, such as oxycodone and hydrocodone, also were the same in 2017 as 2016, at 4.4 per 100,000.

Looking at trends over time since 1999, the rate of increase in drug overdose deaths had risen slowly since 1999 and stabilized in the mid-2000s. However, beginning in 2012, rates have increased steeply, particularly for males.

“Male rates were significantly higher than female rates for all years,” reported Dr. Hedegaard and her coauthors (P less than .05). Though female drug overdose death rates have climbed from 3.9 to 14.4 per 100,000 since 1999, the male death rate has gone from 8.2 to 29.1 per 100,000 during the study period.

“Life expectancy gives us a snapshot of the nation’s overall health and these sobering statistics are a wakeup call that we are losing too many Americans, too early and too often, to conditions that are preventable. CDC is committed to putting science into action to protect U.S. health, but we must all work together to reverse this trend and help ensure that all Americans live longer and healthier lives,” said Dr. Redfield.

[email protected]

Average life expectancy fell in the United States fell from 78.7 years to 78.6 years from 2016 to 2017, according to a new report on the nation’s health. The decrease is primarily attributable to increases in suicide and drug overdose rates, according to new data from the Centers for Disease Control (CDC).

Darwin Brandis/gettyimages

“The latest CDC data show that the U.S. life expectancy has declined over the past few years. Tragically, this troubling trend is largely driven by deaths from drug overdose and suicide,” said CDC Director Robert Redfield, MD, in a statement.

Two subreports that looked specifically at suicide mortality and drug overdose deaths mapped out where, when, and for whom the sharpest increases in mortality are being seen.

For suicide, though rates have increased by 33% overall for both men and women since 1999, the greatest annual increases in suicide rates have happened since 2006, according to a new report from the CDC’s National Center for Health Statistics (NCHS).

Overall, suicide rates have climbed from 10.5 to 14.0 per 100,000 individuals, with statistically significant increases in suicide rates among all age groups except those aged 75 years and older.

Suicide rates rose more steeply in the most rural counties. The age-adjusted increase in the most rural counties was 53%, compared with an increase of 16% in suicide rates for the nation’s most urban counties over the 1999-2017 time period.

Over the entire period studied, men were more likely than women to experience suicide, as rates rose among most age groups. For example, the rates of suicide for men aged 15-24 years rose from 16.8 to 22.7 per 100,000; for women in that age group, suicide rates went from 3.0 to 5.8 per 100,000.

Though suicide has remained the 10th leading cause of death overall in the United States, suicide was the second leading cause of death for adolescents and young adults (aged 10-34) in 2016, and the fourth leading cause of death for those aged 35-54 in that year.

These increases come despite a goal set by the CDC and a national coalition of health partners to reduce suicide rates to 10.2 per 100,000 by 2020, as part of the Healthy People 2020 initiative, noted Molly Hedegaard, MD, of NCHS, and her coauthors, in the suicide mortality data briefing.

Drug overdoses increased by nearly 10% in one year, with the highest rates seen in adults aged 25-54 years, according to a second CDC data briefing.

The number of people who died of drug overdoses in the United States in 2017 was 70,237. This represents a year-over-year age-adjusted increase of 9.6%, from 19.8 to 21.7 per 100,000 individuals, said Dr. Hedegaard and the coauthors of the drug overdose mortality report.

Reflecting known national trends in opioid use disorder, age-adjusted drug overdose deaths were highest in the states of West Virginia, Ohio, and Pennsylvania, where rates were 57.8, 46.3, and 44.3 per 100,000 residents, respectively. The District of Columbia had the fourth-highest age adjusted drug overdose death rate, at 44 per 100,000.

Twenty states, clustered primarily in the Eastern half of the United States, “had age-adjusted drug overdose death rate that were statistically higher than the national rate,” wrote Dr. Hedegaard and her coauthors.

Compared with 1999, more than six times as many adults in older midlife (aged 55-64 years) died from drug overdoses in 2017 (4.2 versus 28 per 100,000).

Adults aged 25-34 years, 35-44 years, and 45-54 years also had significant increases in drug overdose rates; in 2017, rates were 38.4, 29, and 37.7 per 100,000, respectively. Adolescent and young adults died from drug overdoses at a rate of 12.6 per 100,000, and those over 65 years old had a death rate of 6.9 per 100,000.

Deaths attributable to synthetic opioid use, excluding methadone, rose by 45% in just one year, going from 6.2 to 9.0 per 100,000 nationally. In 1999, synthetic opioids other than methadone were implicated in just 0.3 per 100,000 deaths. Synthetic opioids include fentanyl and fentanyl analogs, such as carfentanyl.

Deaths involving heroin remained stable from 2016 to 2017, at 4.9 per 100,000. Deaths attributable to natural and semisynthetic prescription opioids, such as oxycodone and hydrocodone, also were the same in 2017 as 2016, at 4.4 per 100,000.

Looking at trends over time since 1999, the rate of increase in drug overdose deaths had risen slowly since 1999 and stabilized in the mid-2000s. However, beginning in 2012, rates have increased steeply, particularly for males.

“Male rates were significantly higher than female rates for all years,” reported Dr. Hedegaard and her coauthors (P less than .05). Though female drug overdose death rates have climbed from 3.9 to 14.4 per 100,000 since 1999, the male death rate has gone from 8.2 to 29.1 per 100,000 during the study period.

“Life expectancy gives us a snapshot of the nation’s overall health and these sobering statistics are a wakeup call that we are losing too many Americans, too early and too often, to conditions that are preventable. CDC is committed to putting science into action to protect U.S. health, but we must all work together to reverse this trend and help ensure that all Americans live longer and healthier lives,” said Dr. Redfield.

[email protected]

Average life expectancy fell in the United States fell from 78.7 years to 78.6 years from 2016 to 2017, according to a new report on the nation’s health. The decrease is primarily attributable to increases in suicide and drug overdose rates, according to new data from the Centers for Disease Control (CDC).

Darwin Brandis/gettyimages

“The latest CDC data show that the U.S. life expectancy has declined over the past few years. Tragically, this troubling trend is largely driven by deaths from drug overdose and suicide,” said CDC Director Robert Redfield, MD, in a statement.

Two subreports that looked specifically at suicide mortality and drug overdose deaths mapped out where, when, and for whom the sharpest increases in mortality are being seen.

For suicide, though rates have increased by 33% overall for both men and women since 1999, the greatest annual increases in suicide rates have happened since 2006, according to a new report from the CDC’s National Center for Health Statistics (NCHS).

Overall, suicide rates have climbed from 10.5 to 14.0 per 100,000 individuals, with statistically significant increases in suicide rates among all age groups except those aged 75 years and older.

Suicide rates rose more steeply in the most rural counties. The age-adjusted increase in the most rural counties was 53%, compared with an increase of 16% in suicide rates for the nation’s most urban counties over the 1999-2017 time period.

Over the entire period studied, men were more likely than women to experience suicide, as rates rose among most age groups. For example, the rates of suicide for men aged 15-24 years rose from 16.8 to 22.7 per 100,000; for women in that age group, suicide rates went from 3.0 to 5.8 per 100,000.

Though suicide has remained the 10th leading cause of death overall in the United States, suicide was the second leading cause of death for adolescents and young adults (aged 10-34) in 2016, and the fourth leading cause of death for those aged 35-54 in that year.

These increases come despite a goal set by the CDC and a national coalition of health partners to reduce suicide rates to 10.2 per 100,000 by 2020, as part of the Healthy People 2020 initiative, noted Molly Hedegaard, MD, of NCHS, and her coauthors, in the suicide mortality data briefing.

Drug overdoses increased by nearly 10% in one year, with the highest rates seen in adults aged 25-54 years, according to a second CDC data briefing.

The number of people who died of drug overdoses in the United States in 2017 was 70,237. This represents a year-over-year age-adjusted increase of 9.6%, from 19.8 to 21.7 per 100,000 individuals, said Dr. Hedegaard and the coauthors of the drug overdose mortality report.

Reflecting known national trends in opioid use disorder, age-adjusted drug overdose deaths were highest in the states of West Virginia, Ohio, and Pennsylvania, where rates were 57.8, 46.3, and 44.3 per 100,000 residents, respectively. The District of Columbia had the fourth-highest age adjusted drug overdose death rate, at 44 per 100,000.

Twenty states, clustered primarily in the Eastern half of the United States, “had age-adjusted drug overdose death rate that were statistically higher than the national rate,” wrote Dr. Hedegaard and her coauthors.

Compared with 1999, more than six times as many adults in older midlife (aged 55-64 years) died from drug overdoses in 2017 (4.2 versus 28 per 100,000).

Adults aged 25-34 years, 35-44 years, and 45-54 years also had significant increases in drug overdose rates; in 2017, rates were 38.4, 29, and 37.7 per 100,000, respectively. Adolescent and young adults died from drug overdoses at a rate of 12.6 per 100,000, and those over 65 years old had a death rate of 6.9 per 100,000.

Deaths attributable to synthetic opioid use, excluding methadone, rose by 45% in just one year, going from 6.2 to 9.0 per 100,000 nationally. In 1999, synthetic opioids other than methadone were implicated in just 0.3 per 100,000 deaths. Synthetic opioids include fentanyl and fentanyl analogs, such as carfentanyl.

Deaths involving heroin remained stable from 2016 to 2017, at 4.9 per 100,000. Deaths attributable to natural and semisynthetic prescription opioids, such as oxycodone and hydrocodone, also were the same in 2017 as 2016, at 4.4 per 100,000.

Looking at trends over time since 1999, the rate of increase in drug overdose deaths had risen slowly since 1999 and stabilized in the mid-2000s. However, beginning in 2012, rates have increased steeply, particularly for males.

“Male rates were significantly higher than female rates for all years,” reported Dr. Hedegaard and her coauthors (P less than .05). Though female drug overdose death rates have climbed from 3.9 to 14.4 per 100,000 since 1999, the male death rate has gone from 8.2 to 29.1 per 100,000 during the study period.

“Life expectancy gives us a snapshot of the nation’s overall health and these sobering statistics are a wakeup call that we are losing too many Americans, too early and too often, to conditions that are preventable. CDC is committed to putting science into action to protect U.S. health, but we must all work together to reverse this trend and help ensure that all Americans live longer and healthier lives,” said Dr. Redfield.

[email protected]

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

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Spotify

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Physical activity may count more for women who keep the pounds off. Also today, there may be a link between vitamin D levels and atopic dermatitis in children, nerve growth factor antibody cuts osteoarthritis pain with low adverse effects, and how you can harness the power of the urine test in pain care.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

The National Institutes of Health is deeply concerned about the work just presented at the Second International Summit on Human Genome Editing in Hong Kong by Dr. He Jiankui, who described his effort using CRISPR-Cas9 on human embryos to disable the CCR5 gene. He claims that the two embryos were subsequently implanted, and infant twins have been born.

This work represents a deeply disturbing willingness by Dr. He and his team to flout international ethical norms. The project was largely carried out in secret, the medical necessity for inactivation of CCR5 in these infants is utterly unconvincing, the informed consent process appears highly questionable, and the possibility of damaging off-target effects has not been satisfactorily explored. It is profoundly unfortunate that the first apparent application of this powerful technique to the human germline has been carried out so irresponsibly.

The need for development of binding international consensus on setting limits for this kind of research, now being debated in Hong Kong, has never been more apparent. Without such limits, the world will face the serious risk of a deluge of similarly ill-considered and unethical projects.

Should such epic scientific misadventures proceed, a technology with enormous promise for prevention and treatment of disease will be overshadowed by justifiable public outrage, fear, and disgust.

Lest there be any doubt, and as we have stated previously, NIH does not support the use of gene-editing technologies in human embryos.

Francis S. Collins, M.D., Ph.D. is director of the National Institutes of Health. His comments were made in a statement Nov. 28.

The National Institutes of Health is deeply concerned about the work just presented at the Second International Summit on Human Genome Editing in Hong Kong by Dr. He Jiankui, who described his effort using CRISPR-Cas9 on human embryos to disable the CCR5 gene. He claims that the two embryos were subsequently implanted, and infant twins have been born.

This work represents a deeply disturbing willingness by Dr. He and his team to flout international ethical norms. The project was largely carried out in secret, the medical necessity for inactivation of CCR5 in these infants is utterly unconvincing, the informed consent process appears highly questionable, and the possibility of damaging off-target effects has not been satisfactorily explored. It is profoundly unfortunate that the first apparent application of this powerful technique to the human germline has been carried out so irresponsibly.

The need for development of binding international consensus on setting limits for this kind of research, now being debated in Hong Kong, has never been more apparent. Without such limits, the world will face the serious risk of a deluge of similarly ill-considered and unethical projects.

Should such epic scientific misadventures proceed, a technology with enormous promise for prevention and treatment of disease will be overshadowed by justifiable public outrage, fear, and disgust.

Lest there be any doubt, and as we have stated previously, NIH does not support the use of gene-editing technologies in human embryos.

Francis S. Collins, M.D., Ph.D. is director of the National Institutes of Health. His comments were made in a statement Nov. 28.

The National Institutes of Health is deeply concerned about the work just presented at the Second International Summit on Human Genome Editing in Hong Kong by Dr. He Jiankui, who described his effort using CRISPR-Cas9 on human embryos to disable the CCR5 gene. He claims that the two embryos were subsequently implanted, and infant twins have been born.

This work represents a deeply disturbing willingness by Dr. He and his team to flout international ethical norms. The project was largely carried out in secret, the medical necessity for inactivation of CCR5 in these infants is utterly unconvincing, the informed consent process appears highly questionable, and the possibility of damaging off-target effects has not been satisfactorily explored. It is profoundly unfortunate that the first apparent application of this powerful technique to the human germline has been carried out so irresponsibly.

The need for development of binding international consensus on setting limits for this kind of research, now being debated in Hong Kong, has never been more apparent. Without such limits, the world will face the serious risk of a deluge of similarly ill-considered and unethical projects.

Should such epic scientific misadventures proceed, a technology with enormous promise for prevention and treatment of disease will be overshadowed by justifiable public outrage, fear, and disgust.

Lest there be any doubt, and as we have stated previously, NIH does not support the use of gene-editing technologies in human embryos.

Francis S. Collins, M.D., Ph.D. is director of the National Institutes of Health. His comments were made in a statement Nov. 28.

From GAP 2018, Lorenzo Norris, MD, welcome Ashwin Patkar, MD, to discuss the opioid epidemic and how North Carolina is approaching it systemically. And later, Dr. RK knows that some of your patients are blue this time of year, she joins us to talk about what that is and what you can do about it.

In an evidence-based review, Dr. Patkar overviews the issue and includes dosages and references for FDA-approved buprenophine and burprenorphine/naloxone formulation. Click here to read that review.
Amazon Alexa
Apple Podcasts
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Spotify

From GAP 2018, Lorenzo Norris, MD, welcome Ashwin Patkar, MD, to discuss the opioid epidemic and how North Carolina is approaching it systemically. And later, Dr. RK knows that some of your patients are blue this time of year, she joins us to talk about what that is and what you can do about it.

In an evidence-based review, Dr. Patkar overviews the issue and includes dosages and references for FDA-approved buprenophine and burprenorphine/naloxone formulation. Click here to read that review.
Amazon Alexa
Apple Podcasts
Google Podcasts  ​​​​​
Spotify

From GAP 2018, Lorenzo Norris, MD, welcome Ashwin Patkar, MD, to discuss the opioid epidemic and how North Carolina is approaching it systemically. And later, Dr. RK knows that some of your patients are blue this time of year, she joins us to talk about what that is and what you can do about it.

In an evidence-based review, Dr. Patkar overviews the issue and includes dosages and references for FDA-approved buprenophine and burprenorphine/naloxone formulation. Click here to read that review.
Amazon Alexa
Apple Podcasts
Google Podcasts  ​​​​​
Spotify

The jury is still out on using marijuana for pain. Also today, comorbid depression and anxiety are linked to double the risk of diabetes, abortion rates continue to fall, and staying up-to-date on screening decreases risk for colorectal cancer death.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

The jury is still out on using marijuana for pain. Also today, comorbid depression and anxiety are linked to double the risk of diabetes, abortion rates continue to fall, and staying up-to-date on screening decreases risk for colorectal cancer death.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

The jury is still out on using marijuana for pain. Also today, comorbid depression and anxiety are linked to double the risk of diabetes, abortion rates continue to fall, and staying up-to-date on screening decreases risk for colorectal cancer death.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Health care is more effective when patients understand what they can do to be healthier. But many patients cannot read routine preventive information. To help busy clinicians learn more about what they can do to support patient wellness, the Indian Health Service (IHs) Health Literacy workgroup has developed a 20-minute health literacy and plain-language training module.

The IHS also is:

• Pretesting printed educational materials through focus groups and in-depth interviews to ensure messages are clear;
• Revising the IHS website;
• Hosting webinars on health literacy; and
•  Planning to refresh and promote “As Me 3” campaign, which encourages patients to ask 3 specific questions of their providers to better understand their conditions.

In addition to taking the training module, available at the Learning Management System, the IHS suggests clinicians participate in ongoing training in health literacy, plain language and culturally and linguistically appropriate services; use the “health factor” tab in the electronic health record to assess and document the patient’s level of understanding; and learn about the teach-back technique to enhance patients’ understanding.

Health care is more effective when patients understand what they can do to be healthier. But many patients cannot read routine preventive information. To help busy clinicians learn more about what they can do to support patient wellness, the Indian Health Service (IHs) Health Literacy workgroup has developed a 20-minute health literacy and plain-language training module.

The IHS also is:

• Pretesting printed educational materials through focus groups and in-depth interviews to ensure messages are clear;
• Revising the IHS website;
• Hosting webinars on health literacy; and
•  Planning to refresh and promote “As Me 3” campaign, which encourages patients to ask 3 specific questions of their providers to better understand their conditions.

In addition to taking the training module, available at the Learning Management System, the IHS suggests clinicians participate in ongoing training in health literacy, plain language and culturally and linguistically appropriate services; use the “health factor” tab in the electronic health record to assess and document the patient’s level of understanding; and learn about the teach-back technique to enhance patients’ understanding.

Health care is more effective when patients understand what they can do to be healthier. But many patients cannot read routine preventive information. To help busy clinicians learn more about what they can do to support patient wellness, the Indian Health Service (IHs) Health Literacy workgroup has developed a 20-minute health literacy and plain-language training module.

The IHS also is:

• Pretesting printed educational materials through focus groups and in-depth interviews to ensure messages are clear;
• Revising the IHS website;
• Hosting webinars on health literacy; and
•  Planning to refresh and promote “As Me 3” campaign, which encourages patients to ask 3 specific questions of their providers to better understand their conditions.

In addition to taking the training module, available at the Learning Management System, the IHS suggests clinicians participate in ongoing training in health literacy, plain language and culturally and linguistically appropriate services; use the “health factor” tab in the electronic health record to assess and document the patient’s level of understanding; and learn about the teach-back technique to enhance patients’ understanding.

Smoke-free policies are linked to lower blood pressure. Also today, bariatric surgery increases the risk for suicide and self-harm, a novel topical JAK inhibitor shows promise for atopic dermatitis, and livers infected with hepatitis C are safe for transplant.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Smoke-free policies are linked to lower blood pressure. Also today, bariatric surgery increases the risk for suicide and self-harm, a novel topical JAK inhibitor shows promise for atopic dermatitis, and livers infected with hepatitis C are safe for transplant.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Smoke-free policies are linked to lower blood pressure. Also today, bariatric surgery increases the risk for suicide and self-harm, a novel topical JAK inhibitor shows promise for atopic dermatitis, and livers infected with hepatitis C are safe for transplant.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Numerous highly efficacious treatment modalities exist in dermatology, yet patients may be highly wary of their possible adverse events, even when those risks are rare.^1,2 Such fears can lead to poor medication adherence and treatment refusal. A key determinant in successful patient-provider care is to effectively communicate risk. The communication of risk is hampered by the lack of any common currency for comparing risks. The development of a standardized unit of risk could help facilitate risk comparisons, allowing physicians and patients to put risk levels into better perspective.

One easily relatable event is the risk of injury in an automobile crash. Driving, whether to the dermatology clinic for a monitoring visit or to the supermarket for weekly groceries, is associated with risk of injury and death. The risk of automobile-related injury warranting a visit to the emergency department could provide a comparator that physicians can use to give patients a more objective sense of treatment risks or to introduce the justification of a monitoring visit. The objective of this study was to develop a standard risk unit based on the lifetime risk (LTR) of automobile injury and to compare this unit of risk to various risks of dermatologic treatments.

Methods

Literature Review
We first identified common risks in dermatology that would be illustrative and then identified keywords. PubMed searches for articles indexed for MEDLINE from November 1996 to February 2017 were performed combining the following terms: (relative risk, odds ratio, lifetime risk) and (isotretinoin, IBD; melanoma, SCC, transplantation; indoor tanning, BCC, SCC; transplant and SCC; biologics and tuberculosis; hydroxychloroquine retinal toxicity; psoriasis and psoriatic arthritis). An additional search was performed in June 2018 including the term blindness and injectable fillers. Our search combined these terms in numerous ways. Results were focused on meta-analyses and observational studies.

The references of relevant studies were included. Articles not focused on meta-analyses but rather on observational studies were individually analyzed for quality and bias using the 9-point Newcastle-Ottawa Scale, with a score of 7 or more as a cutoff for inclusion.

Determination of Risk Comparators
Data from the 2016 National Safety Council’s Injury Facts report were searched for nonmedical-related risk comparators, such as the risk of death by dog attack, by lightning, and by fire or smoke.³ Data from the 2015 US Department of Transportation Traffic Safety Facts were searched for relatable risk comparators, such as the LTR of automobile death and injury.⁴

Definitions
Automobile injury was defined as an injury warranting a visit to the emergency department.⁵ Automobile was defined as a road vehicle with 4 wheels and powered by an internal combustion engine or electric motor.⁶ This definition excluded light trucks, large trucks, and motorcycles.

LTR Calculation
Lifetime risk was used as the comparative measure. Lifetime risk is a type of absolute risk that depicts the probability that a specific disease or event will occur in an individual’s lifespan. The LTRof developing a disease or adverse event due to a dermatologic therapy or interventionwas denoted as LTR_{adverse event} and calculated by the following equation^7,8:

In this equation, LTR_{general population} is the LTR of developing the disease or adverse event without being subject to the therapy or intervention, and RR_intervention is the relative risk (RR) from previously published RR data (relating to the development of the disease in question or an adverse event of the intervention). The use of equation (1) holds true only when the absolute risk of developing the disease or adverse event (LTR_{general population}) is low.⁷ Although the calculation of an LTR using a constant lifetime RR may require major approximations, studies evaluating the variation of RR over time are sparse.^7,9 The Newcastle-Ottawa Scale was used to control such variance; only high-quality, nonrandomized studies were included. Although the use of residual LTR would be preferable, as LTR depends on age, such epidemiological data do not exist for complex diseases.

When not available, the LTR_{general population} was calculated from the rate of disease (cases per 100,000 individuals per year) multiplied by the average lifespan of an American (78.8 years)¹⁰:

When an odds ratio (OR) was presented, its conversion to RR followed¹¹:

In this equation, R_C is the absolute risk in the unexposed group. If the prevalence of the disease was considered low, the rare disease assumption was implemented as the following^11,12:

The use of this approximation overestimates the LTR of an event. From a patient perspective, this approach is conservative. If prior LTR values were available, such as the LTR of automobile injury, automobile death, or other intervention, they were used without the need for calculation.

Unit Comparator
The LTRs of all adverse events were normalized to a unit comparator, using the LTR of an automobile injury as reference point, denoted as 1 risk unit (RU):

This equation allows for quick comparison of the magnitude of LTRs between events. Events with an RU less than 1 are less likely to occur than the risk of automobile injury; events with an RU greater than 1 are more likely than the risk of automobile injury. All RR, LTR, and unit comparators were presented as a single pooled estimate of their respective upper-limit CIs. The use of the upper-limit CI conservatively overestimates the LTR of an event.

Results

Ten dermatologic interventions were identified as illustrative, to be presented alongside the risk of automobile injury and death. The LTR of automobile injury was 32%, defined as 1.0 RU. The LTR of automobile death was 0.89% (1/36 RU).

Two events had LTRs roughly similar to automobile injury: development of a subsequent basal cell carcinoma within 3 years (1.4 RU) and development of a squamous cell carcinoma (SCC) secondary to indoor tanning (1.6 RU). Development of SCC following organ transplantation (34 RU) was considerably more likely than automobile injury. All other identified events had lower RUs than automobile injury (Table). Three events with small RUs included tuberculosis development with a tumor necrosis factor α inhibitor (1/32 RU), Crohn disease development with isotretinoin (1/41 RU), and blindness following facial hyaluronic acid injection (1/80 RU). The LTR of death by dog attack (1/42,436 RU) and death by lightning strike (1/36,542 RU) also had small RUs.

The unit comparators from the Table were adapted into graphic form to depict risk relative to the risk of automobile injury (Figure).

Comment

Numerous interventions in dermatology offer much less risk of an adverse event than the LTR of automobile injury. However, this concept of risk includes only the likelihood of development of an event, not the severity of the measured event, as our numerical and visual tool objectively captures the related risks using an RU comparator. Such use of a standardized RU demonstrates the essence of risk; “zero risk” does not exist, and each intervention or treatment, albeit how small, must be justified in concordance with other types of risk, such as the automobile.

The development of adverse events secondary to dermatologic intervention or therapy, for which monitoring visits are utilized, were used as important comparators to the risk of automobile injury. The continuous practice of monitoring visits may increase patient’s fears regarding possible adverse events secondary to therapy. Hydroxychloroquine retinal toxicity (1/16 RU) and psoriatic arthritis development following severe psoriasis (1/3.9 RU) were less likely to occur than automobile injury. The development of abnormal blood counts or blood tests secondary to therapy or intervention could not be formatted into an RU. The use of equation (1) for the calculation of LTR_{adverse event}holds true only when the absolute risk of developing the adverse event in the general population—in this case, abnormal blood counts or blood tests—is low.⁷

Although the unit comparator allows for the comparison of different dermatologic risk, a limitation of the RU model and its visual tool are a dependence on RR, a value that changes following publication of new studies. A solution was the use of a single pooled estimate to represent the upper-limit CIs of LTR. This practice overestimates risk. As with RR, new automobile injury rates are published annually.¹⁰ In the last 5 years, the LTR of automobile injury has stayed relatively constant: between 32% and 33%.⁴ Although the RU calculations and Figure included a wide variety of interventions in dermatology, select clinical situations were not included. It is beyond the scope of this article to systematically review all risk in dermatology but rather introduce the concept of the RU founded on automobile-associated risks. With the introduction of a methodical framework, the reader is invited to calculate RUs pertinent to their clinical interests.

Any intervention or treatment in dermatology is accompanied by risk. The use of a unit comparator using an easily relatable event—the LTR of automobile injury—allows the patient to easily compare risk and internally justify the practice of monitoring visits. Inclusion of a visual tool, such as the Figure, might alleviate many irrational fears that accompany some of the highly effective treatments and interventions used in dermatology and thus lead to better patient outcomes.

Acknowledgment
We thank Taranjeet Singh, MS (Dunn, North Carolina), for her comments on an earlier version of the manuscript.

Numerous highly efficacious treatment modalities exist in dermatology, yet patients may be highly wary of their possible adverse events, even when those risks are rare.^1,2 Such fears can lead to poor medication adherence and treatment refusal. A key determinant in successful patient-provider care is to effectively communicate risk. The communication of risk is hampered by the lack of any common currency for comparing risks. The development of a standardized unit of risk could help facilitate risk comparisons, allowing physicians and patients to put risk levels into better perspective.

One easily relatable event is the risk of injury in an automobile crash. Driving, whether to the dermatology clinic for a monitoring visit or to the supermarket for weekly groceries, is associated with risk of injury and death. The risk of automobile-related injury warranting a visit to the emergency department could provide a comparator that physicians can use to give patients a more objective sense of treatment risks or to introduce the justification of a monitoring visit. The objective of this study was to develop a standard risk unit based on the lifetime risk (LTR) of automobile injury and to compare this unit of risk to various risks of dermatologic treatments.

Methods

Literature Review
We first identified common risks in dermatology that would be illustrative and then identified keywords. PubMed searches for articles indexed for MEDLINE from November 1996 to February 2017 were performed combining the following terms: (relative risk, odds ratio, lifetime risk) and (isotretinoin, IBD; melanoma, SCC, transplantation; indoor tanning, BCC, SCC; transplant and SCC; biologics and tuberculosis; hydroxychloroquine retinal toxicity; psoriasis and psoriatic arthritis). An additional search was performed in June 2018 including the term blindness and injectable fillers. Our search combined these terms in numerous ways. Results were focused on meta-analyses and observational studies.

The references of relevant studies were included. Articles not focused on meta-analyses but rather on observational studies were individually analyzed for quality and bias using the 9-point Newcastle-Ottawa Scale, with a score of 7 or more as a cutoff for inclusion.

Determination of Risk Comparators
Data from the 2016 National Safety Council’s Injury Facts report were searched for nonmedical-related risk comparators, such as the risk of death by dog attack, by lightning, and by fire or smoke.³ Data from the 2015 US Department of Transportation Traffic Safety Facts were searched for relatable risk comparators, such as the LTR of automobile death and injury.⁴

Definitions
Automobile injury was defined as an injury warranting a visit to the emergency department.⁵ Automobile was defined as a road vehicle with 4 wheels and powered by an internal combustion engine or electric motor.⁶ This definition excluded light trucks, large trucks, and motorcycles.

LTR Calculation
Lifetime risk was used as the comparative measure. Lifetime risk is a type of absolute risk that depicts the probability that a specific disease or event will occur in an individual’s lifespan. The LTRof developing a disease or adverse event due to a dermatologic therapy or interventionwas denoted as LTR_{adverse event} and calculated by the following equation^7,8:

In this equation, LTR_{general population} is the LTR of developing the disease or adverse event without being subject to the therapy or intervention, and RR_intervention is the relative risk (RR) from previously published RR data (relating to the development of the disease in question or an adverse event of the intervention). The use of equation (1) holds true only when the absolute risk of developing the disease or adverse event (LTR_{general population}) is low.⁷ Although the calculation of an LTR using a constant lifetime RR may require major approximations, studies evaluating the variation of RR over time are sparse.^7,9 The Newcastle-Ottawa Scale was used to control such variance; only high-quality, nonrandomized studies were included. Although the use of residual LTR would be preferable, as LTR depends on age, such epidemiological data do not exist for complex diseases.

When not available, the LTR_{general population} was calculated from the rate of disease (cases per 100,000 individuals per year) multiplied by the average lifespan of an American (78.8 years)¹⁰:

When an odds ratio (OR) was presented, its conversion to RR followed¹¹:

In this equation, R_C is the absolute risk in the unexposed group. If the prevalence of the disease was considered low, the rare disease assumption was implemented as the following^11,12:

The use of this approximation overestimates the LTR of an event. From a patient perspective, this approach is conservative. If prior LTR values were available, such as the LTR of automobile injury, automobile death, or other intervention, they were used without the need for calculation.

Unit Comparator
The LTRs of all adverse events were normalized to a unit comparator, using the LTR of an automobile injury as reference point, denoted as 1 risk unit (RU):

This equation allows for quick comparison of the magnitude of LTRs between events. Events with an RU less than 1 are less likely to occur than the risk of automobile injury; events with an RU greater than 1 are more likely than the risk of automobile injury. All RR, LTR, and unit comparators were presented as a single pooled estimate of their respective upper-limit CIs. The use of the upper-limit CI conservatively overestimates the LTR of an event.

Results

Ten dermatologic interventions were identified as illustrative, to be presented alongside the risk of automobile injury and death. The LTR of automobile injury was 32%, defined as 1.0 RU. The LTR of automobile death was 0.89% (1/36 RU).

Two events had LTRs roughly similar to automobile injury: development of a subsequent basal cell carcinoma within 3 years (1.4 RU) and development of a squamous cell carcinoma (SCC) secondary to indoor tanning (1.6 RU). Development of SCC following organ transplantation (34 RU) was considerably more likely than automobile injury. All other identified events had lower RUs than automobile injury (Table). Three events with small RUs included tuberculosis development with a tumor necrosis factor α inhibitor (1/32 RU), Crohn disease development with isotretinoin (1/41 RU), and blindness following facial hyaluronic acid injection (1/80 RU). The LTR of death by dog attack (1/42,436 RU) and death by lightning strike (1/36,542 RU) also had small RUs.

The unit comparators from the Table were adapted into graphic form to depict risk relative to the risk of automobile injury (Figure).

Comment

Numerous interventions in dermatology offer much less risk of an adverse event than the LTR of automobile injury. However, this concept of risk includes only the likelihood of development of an event, not the severity of the measured event, as our numerical and visual tool objectively captures the related risks using an RU comparator. Such use of a standardized RU demonstrates the essence of risk; “zero risk” does not exist, and each intervention or treatment, albeit how small, must be justified in concordance with other types of risk, such as the automobile.

The development of adverse events secondary to dermatologic intervention or therapy, for which monitoring visits are utilized, were used as important comparators to the risk of automobile injury. The continuous practice of monitoring visits may increase patient’s fears regarding possible adverse events secondary to therapy. Hydroxychloroquine retinal toxicity (1/16 RU) and psoriatic arthritis development following severe psoriasis (1/3.9 RU) were less likely to occur than automobile injury. The development of abnormal blood counts or blood tests secondary to therapy or intervention could not be formatted into an RU. The use of equation (1) for the calculation of LTR_{adverse event}holds true only when the absolute risk of developing the adverse event in the general population—in this case, abnormal blood counts or blood tests—is low.⁷

Although the unit comparator allows for the comparison of different dermatologic risk, a limitation of the RU model and its visual tool are a dependence on RR, a value that changes following publication of new studies. A solution was the use of a single pooled estimate to represent the upper-limit CIs of LTR. This practice overestimates risk. As with RR, new automobile injury rates are published annually.¹⁰ In the last 5 years, the LTR of automobile injury has stayed relatively constant: between 32% and 33%.⁴ Although the RU calculations and Figure included a wide variety of interventions in dermatology, select clinical situations were not included. It is beyond the scope of this article to systematically review all risk in dermatology but rather introduce the concept of the RU founded on automobile-associated risks. With the introduction of a methodical framework, the reader is invited to calculate RUs pertinent to their clinical interests.

Any intervention or treatment in dermatology is accompanied by risk. The use of a unit comparator using an easily relatable event—the LTR of automobile injury—allows the patient to easily compare risk and internally justify the practice of monitoring visits. Inclusion of a visual tool, such as the Figure, might alleviate many irrational fears that accompany some of the highly effective treatments and interventions used in dermatology and thus lead to better patient outcomes.

Acknowledgment
We thank Taranjeet Singh, MS (Dunn, North Carolina), for her comments on an earlier version of the manuscript.

Numerous highly efficacious treatment modalities exist in dermatology, yet patients may be highly wary of their possible adverse events, even when those risks are rare.^1,2 Such fears can lead to poor medication adherence and treatment refusal. A key determinant in successful patient-provider care is to effectively communicate risk. The communication of risk is hampered by the lack of any common currency for comparing risks. The development of a standardized unit of risk could help facilitate risk comparisons, allowing physicians and patients to put risk levels into better perspective.

One easily relatable event is the risk of injury in an automobile crash. Driving, whether to the dermatology clinic for a monitoring visit or to the supermarket for weekly groceries, is associated with risk of injury and death. The risk of automobile-related injury warranting a visit to the emergency department could provide a comparator that physicians can use to give patients a more objective sense of treatment risks or to introduce the justification of a monitoring visit. The objective of this study was to develop a standard risk unit based on the lifetime risk (LTR) of automobile injury and to compare this unit of risk to various risks of dermatologic treatments.

Methods

Literature Review
We first identified common risks in dermatology that would be illustrative and then identified keywords. PubMed searches for articles indexed for MEDLINE from November 1996 to February 2017 were performed combining the following terms: (relative risk, odds ratio, lifetime risk) and (isotretinoin, IBD; melanoma, SCC, transplantation; indoor tanning, BCC, SCC; transplant and SCC; biologics and tuberculosis; hydroxychloroquine retinal toxicity; psoriasis and psoriatic arthritis). An additional search was performed in June 2018 including the term blindness and injectable fillers. Our search combined these terms in numerous ways. Results were focused on meta-analyses and observational studies.

The references of relevant studies were included. Articles not focused on meta-analyses but rather on observational studies were individually analyzed for quality and bias using the 9-point Newcastle-Ottawa Scale, with a score of 7 or more as a cutoff for inclusion.

Determination of Risk Comparators
Data from the 2016 National Safety Council’s Injury Facts report were searched for nonmedical-related risk comparators, such as the risk of death by dog attack, by lightning, and by fire or smoke.³ Data from the 2015 US Department of Transportation Traffic Safety Facts were searched for relatable risk comparators, such as the LTR of automobile death and injury.⁴

Definitions
Automobile injury was defined as an injury warranting a visit to the emergency department.⁵ Automobile was defined as a road vehicle with 4 wheels and powered by an internal combustion engine or electric motor.⁶ This definition excluded light trucks, large trucks, and motorcycles.

LTR Calculation
Lifetime risk was used as the comparative measure. Lifetime risk is a type of absolute risk that depicts the probability that a specific disease or event will occur in an individual’s lifespan. The LTRof developing a disease or adverse event due to a dermatologic therapy or interventionwas denoted as LTR_{adverse event} and calculated by the following equation^7,8:

In this equation, LTR_{general population} is the LTR of developing the disease or adverse event without being subject to the therapy or intervention, and RR_intervention is the relative risk (RR) from previously published RR data (relating to the development of the disease in question or an adverse event of the intervention). The use of equation (1) holds true only when the absolute risk of developing the disease or adverse event (LTR_{general population}) is low.⁷ Although the calculation of an LTR using a constant lifetime RR may require major approximations, studies evaluating the variation of RR over time are sparse.^7,9 The Newcastle-Ottawa Scale was used to control such variance; only high-quality, nonrandomized studies were included. Although the use of residual LTR would be preferable, as LTR depends on age, such epidemiological data do not exist for complex diseases.

When not available, the LTR_{general population} was calculated from the rate of disease (cases per 100,000 individuals per year) multiplied by the average lifespan of an American (78.8 years)¹⁰:

When an odds ratio (OR) was presented, its conversion to RR followed¹¹:

In this equation, R_C is the absolute risk in the unexposed group. If the prevalence of the disease was considered low, the rare disease assumption was implemented as the following^11,12:

The use of this approximation overestimates the LTR of an event. From a patient perspective, this approach is conservative. If prior LTR values were available, such as the LTR of automobile injury, automobile death, or other intervention, they were used without the need for calculation.

Unit Comparator
The LTRs of all adverse events were normalized to a unit comparator, using the LTR of an automobile injury as reference point, denoted as 1 risk unit (RU):

This equation allows for quick comparison of the magnitude of LTRs between events. Events with an RU less than 1 are less likely to occur than the risk of automobile injury; events with an RU greater than 1 are more likely than the risk of automobile injury. All RR, LTR, and unit comparators were presented as a single pooled estimate of their respective upper-limit CIs. The use of the upper-limit CI conservatively overestimates the LTR of an event.

Results

Ten dermatologic interventions were identified as illustrative, to be presented alongside the risk of automobile injury and death. The LTR of automobile injury was 32%, defined as 1.0 RU. The LTR of automobile death was 0.89% (1/36 RU).

Two events had LTRs roughly similar to automobile injury: development of a subsequent basal cell carcinoma within 3 years (1.4 RU) and development of a squamous cell carcinoma (SCC) secondary to indoor tanning (1.6 RU). Development of SCC following organ transplantation (34 RU) was considerably more likely than automobile injury. All other identified events had lower RUs than automobile injury (Table). Three events with small RUs included tuberculosis development with a tumor necrosis factor α inhibitor (1/32 RU), Crohn disease development with isotretinoin (1/41 RU), and blindness following facial hyaluronic acid injection (1/80 RU). The LTR of death by dog attack (1/42,436 RU) and death by lightning strike (1/36,542 RU) also had small RUs.

The unit comparators from the Table were adapted into graphic form to depict risk relative to the risk of automobile injury (Figure).

Comment

Numerous interventions in dermatology offer much less risk of an adverse event than the LTR of automobile injury. However, this concept of risk includes only the likelihood of development of an event, not the severity of the measured event, as our numerical and visual tool objectively captures the related risks using an RU comparator. Such use of a standardized RU demonstrates the essence of risk; “zero risk” does not exist, and each intervention or treatment, albeit how small, must be justified in concordance with other types of risk, such as the automobile.

The development of adverse events secondary to dermatologic intervention or therapy, for which monitoring visits are utilized, were used as important comparators to the risk of automobile injury. The continuous practice of monitoring visits may increase patient’s fears regarding possible adverse events secondary to therapy. Hydroxychloroquine retinal toxicity (1/16 RU) and psoriatic arthritis development following severe psoriasis (1/3.9 RU) were less likely to occur than automobile injury. The development of abnormal blood counts or blood tests secondary to therapy or intervention could not be formatted into an RU. The use of equation (1) for the calculation of LTR_{adverse event}holds true only when the absolute risk of developing the adverse event in the general population—in this case, abnormal blood counts or blood tests—is low.⁷

Although the unit comparator allows for the comparison of different dermatologic risk, a limitation of the RU model and its visual tool are a dependence on RR, a value that changes following publication of new studies. A solution was the use of a single pooled estimate to represent the upper-limit CIs of LTR. This practice overestimates risk. As with RR, new automobile injury rates are published annually.¹⁰ In the last 5 years, the LTR of automobile injury has stayed relatively constant: between 32% and 33%.⁴ Although the RU calculations and Figure included a wide variety of interventions in dermatology, select clinical situations were not included. It is beyond the scope of this article to systematically review all risk in dermatology but rather introduce the concept of the RU founded on automobile-associated risks. With the introduction of a methodical framework, the reader is invited to calculate RUs pertinent to their clinical interests.

Any intervention or treatment in dermatology is accompanied by risk. The use of a unit comparator using an easily relatable event—the LTR of automobile injury—allows the patient to easily compare risk and internally justify the practice of monitoring visits. Inclusion of a visual tool, such as the Figure, might alleviate many irrational fears that accompany some of the highly effective treatments and interventions used in dermatology and thus lead to better patient outcomes.

Acknowledgment
We thank Taranjeet Singh, MS (Dunn, North Carolina), for her comments on an earlier version of the manuscript.

The Diagnosis: X-Linked Ichthyosis

Immunohistochemical staining of a punch biopsy specimen from the left foot with cytokeratin markers AE1/3, 5/6, and 19 showed normal positive uptake. Further workup was recommended, and the patient was referred to genetics for an ichthyosis gene panel. DNA sequencing revealed a c.1121G>A transition in exon 10 of the steroid sulfatase gene, STS, consistent with X-linked ichthyosis (XLI).

X-linked ichthyosis, also known as steroid sulfatase deficiency and X-linked recessive ichthyosis, is a congenital skin disorder classified in 1965 by Wells and Kerr.¹ Ichthyoses are a heterogenous group of acquired and congenital disorders of keratinization that manifest with xerosis, hyperkeratosis, and scaling.² Of more than 20 ichthyoses, XLI is the second most common ichthyosis, with a prevalence of 1 in 6000 males.³ X-linked ichthyosis occurs almost exclusively in males, and although females can be carriers, they rarely exhibit skin manifestations.⁴

X-linked ichthyosis is caused by either a partial or full deletion or mutation in the STS gene on the X chromosome.² The absence of STS activity results in the accumulation of cholesterol sulfate in the stratum corneum, leading to corneocyte cohesion, hyperkeratosis, and impaired skin permeability. The most common clinical phenotype is characterized by polygonal scales concentrated on the upper and lower extremities as well as the trunk (Figure), consistent with our patient's clinical presentation.⁵

X-linked ichthyosis typically presents in the first 6 months of life as generalized desquamation and xerosis that progresses to fine scaling on the trunk and extremities, more commonly and heavily involving the legs; however, the extensor surfaces of the arms also may be affected.⁶ After the neonatal period, fine scaling persists on the trunk and extremities, but scales often become coarser and darker over time. Although scaling is generalized, it typically spares the antecubital and popliteal fossae, palms, soles, and midface. The lateral face, axillae, and neck always remain involved.⁴ The most common extracutaneous manifestations of XLI affect the ocular, genitourinary, and cognitive/behavioral systems. Patients can develop corneal comma-shaped opacities, hypogonadism, cryptorchidism, and an increased risk for testicular cancer. Female carriers may have prolonged delivery of affected neonates.^2,5,7-9 Given the unrelated debilitating neurologic consequences of our patient's presenting subarachnoid hemorrhage, further workup was not pursued into these associations.

Although XLI is most commonly diagnosed in early childhood, it also must be considered in adult patients presenting with severe scaling of the trunk, arms, and legs who have not had prior dermatologic workup. Given the similarity of XLI presentation to other ichthyoses, particularly ichthyosis vulgaris, lamellar ichthyosis, and ichthyosis bullosa of Siemens, genetic analysis is the most accurate diagnostic tool and should be considered in patients with an atypical presentation. Rupioid psoriasis also may be considered and can be confirmed on biopsy. Diagnosis of XLI should prompt symptomatic treatment, genetic counseling, and workup for extracutaneous manifestations.

The Diagnosis: X-Linked Ichthyosis

Immunohistochemical staining of a punch biopsy specimen from the left foot with cytokeratin markers AE1/3, 5/6, and 19 showed normal positive uptake. Further workup was recommended, and the patient was referred to genetics for an ichthyosis gene panel. DNA sequencing revealed a c.1121G>A transition in exon 10 of the steroid sulfatase gene, STS, consistent with X-linked ichthyosis (XLI).

X-linked ichthyosis, also known as steroid sulfatase deficiency and X-linked recessive ichthyosis, is a congenital skin disorder classified in 1965 by Wells and Kerr.¹ Ichthyoses are a heterogenous group of acquired and congenital disorders of keratinization that manifest with xerosis, hyperkeratosis, and scaling.² Of more than 20 ichthyoses, XLI is the second most common ichthyosis, with a prevalence of 1 in 6000 males.³ X-linked ichthyosis occurs almost exclusively in males, and although females can be carriers, they rarely exhibit skin manifestations.⁴

X-linked ichthyosis is caused by either a partial or full deletion or mutation in the STS gene on the X chromosome.² The absence of STS activity results in the accumulation of cholesterol sulfate in the stratum corneum, leading to corneocyte cohesion, hyperkeratosis, and impaired skin permeability. The most common clinical phenotype is characterized by polygonal scales concentrated on the upper and lower extremities as well as the trunk (Figure), consistent with our patient's clinical presentation.⁵

X-linked ichthyosis typically presents in the first 6 months of life as generalized desquamation and xerosis that progresses to fine scaling on the trunk and extremities, more commonly and heavily involving the legs; however, the extensor surfaces of the arms also may be affected.⁶ After the neonatal period, fine scaling persists on the trunk and extremities, but scales often become coarser and darker over time. Although scaling is generalized, it typically spares the antecubital and popliteal fossae, palms, soles, and midface. The lateral face, axillae, and neck always remain involved.⁴ The most common extracutaneous manifestations of XLI affect the ocular, genitourinary, and cognitive/behavioral systems. Patients can develop corneal comma-shaped opacities, hypogonadism, cryptorchidism, and an increased risk for testicular cancer. Female carriers may have prolonged delivery of affected neonates.^2,5,7-9 Given the unrelated debilitating neurologic consequences of our patient's presenting subarachnoid hemorrhage, further workup was not pursued into these associations.

Although XLI is most commonly diagnosed in early childhood, it also must be considered in adult patients presenting with severe scaling of the trunk, arms, and legs who have not had prior dermatologic workup. Given the similarity of XLI presentation to other ichthyoses, particularly ichthyosis vulgaris, lamellar ichthyosis, and ichthyosis bullosa of Siemens, genetic analysis is the most accurate diagnostic tool and should be considered in patients with an atypical presentation. Rupioid psoriasis also may be considered and can be confirmed on biopsy. Diagnosis of XLI should prompt symptomatic treatment, genetic counseling, and workup for extracutaneous manifestations.

The Diagnosis: X-Linked Ichthyosis

Immunohistochemical staining of a punch biopsy specimen from the left foot with cytokeratin markers AE1/3, 5/6, and 19 showed normal positive uptake. Further workup was recommended, and the patient was referred to genetics for an ichthyosis gene panel. DNA sequencing revealed a c.1121G>A transition in exon 10 of the steroid sulfatase gene, STS, consistent with X-linked ichthyosis (XLI).

X-linked ichthyosis, also known as steroid sulfatase deficiency and X-linked recessive ichthyosis, is a congenital skin disorder classified in 1965 by Wells and Kerr.¹ Ichthyoses are a heterogenous group of acquired and congenital disorders of keratinization that manifest with xerosis, hyperkeratosis, and scaling.² Of more than 20 ichthyoses, XLI is the second most common ichthyosis, with a prevalence of 1 in 6000 males.³ X-linked ichthyosis occurs almost exclusively in males, and although females can be carriers, they rarely exhibit skin manifestations.⁴

X-linked ichthyosis is caused by either a partial or full deletion or mutation in the STS gene on the X chromosome.² The absence of STS activity results in the accumulation of cholesterol sulfate in the stratum corneum, leading to corneocyte cohesion, hyperkeratosis, and impaired skin permeability. The most common clinical phenotype is characterized by polygonal scales concentrated on the upper and lower extremities as well as the trunk (Figure), consistent with our patient's clinical presentation.⁵

X-linked ichthyosis typically presents in the first 6 months of life as generalized desquamation and xerosis that progresses to fine scaling on the trunk and extremities, more commonly and heavily involving the legs; however, the extensor surfaces of the arms also may be affected.⁶ After the neonatal period, fine scaling persists on the trunk and extremities, but scales often become coarser and darker over time. Although scaling is generalized, it typically spares the antecubital and popliteal fossae, palms, soles, and midface. The lateral face, axillae, and neck always remain involved.⁴ The most common extracutaneous manifestations of XLI affect the ocular, genitourinary, and cognitive/behavioral systems. Patients can develop corneal comma-shaped opacities, hypogonadism, cryptorchidism, and an increased risk for testicular cancer. Female carriers may have prolonged delivery of affected neonates.^2,5,7-9 Given the unrelated debilitating neurologic consequences of our patient's presenting subarachnoid hemorrhage, further workup was not pursued into these associations.

Although XLI is most commonly diagnosed in early childhood, it also must be considered in adult patients presenting with severe scaling of the trunk, arms, and legs who have not had prior dermatologic workup. Given the similarity of XLI presentation to other ichthyoses, particularly ichthyosis vulgaris, lamellar ichthyosis, and ichthyosis bullosa of Siemens, genetic analysis is the most accurate diagnostic tool and should be considered in patients with an atypical presentation. Rupioid psoriasis also may be considered and can be confirmed on biopsy. Diagnosis of XLI should prompt symptomatic treatment, genetic counseling, and workup for extracutaneous manifestations.

Two probiotic products did not significantly impact children with gastroenteritis. Also today, all patients with VTE have a high risk of recurrence, the REDUCE-IT study establishes a “phenomenal” triglyceride theory, and new data on patients with gout suggest a treat-to-target approach.

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Apple Podcasts
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Spotify

Two probiotic products did not significantly impact children with gastroenteritis. Also today, all patients with VTE have a high risk of recurrence, the REDUCE-IT study establishes a “phenomenal” triglyceride theory, and new data on patients with gout suggest a treat-to-target approach.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Two probiotic products did not significantly impact children with gastroenteritis. Also today, all patients with VTE have a high risk of recurrence, the REDUCE-IT study establishes a “phenomenal” triglyceride theory, and new data on patients with gout suggest a treat-to-target approach.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify