Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

rfranki@frontlinemedcom.com

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

rfranki@frontlinemedcom.com

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

rfranki@frontlinemedcom.com

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The Diagnosis: Hyperkeratosis Lenticularis Perstans

A shave biopsy of a lesion on the right leg was performed. Histopathology revealed a discrete papule with overlying compact hyperkeratosis. There was parakeratosis with an absent granular layer and a lichenoid lymphocytic infiltrate within the papillary dermis (Figure). Given the clinical context, these changes were consistent with a diagnosis of hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease.

The patient was started on tretinoin cream 0.1% nightly for 3 months and triamcinolone ointment 0.1% as needed for pruritus but showed no clinical response. Given the benign nature of the condition and because the lesions were asymptomatic, additional treatment options were not pursued.

Originally described by Flegel¹ in 1958, HLP is a rare skin disorder commonly seen in white individuals with onset in the fourth or fifth decades of life.^1,2 While most cases are sporadic,^3-6 HLP also has been associated with autosomal dominant inheritance.^7-10

Patients with HLP typically present with multiple 1- to 5-mm reddish-brown, hyperkeratotic, scaly papules that reveal a moist, erythematous base with pinpoint bleeding upon removal of the scale. Lesions usually are distributed symmetrically and most commonly present on the extensor surfaces of the lower legs and dorsal feet.^1,2,7 Lesions also may appear on the extensor surfaces of the arms, pinna, periocular region, antecubital and popliteal fossae, and oral mucosa and also may present as pits on the palms and soles.^2,4,7,8 Furthermore, unilateral and localized variants of HLP have been described.^11,12 Hyperkeratosis lenticularis perstans usually is asymptomatic but can present with mild pruritus or burning.^3,5,13

The etiology and pathogenesis of HLP are unknown. Exposure to UV light has been implicated as an inciting factor¹⁴; however, reports of spontaneous resolution in the summer¹³ and upon treatment with psoralen plus UVA therapy¹⁵ make the role of UV light unclear. Furthermore, investigators disagree as to whether the primary pathogenic event in HLP is an inflammatory process or one of abnormal keratinization.^1,3,7,10 Fernandez-Flores and Manjon¹⁶ suggested HLP is an inflammatory process with periods of exacerbations and remissions after finding mounds of parakeratosis with neutrophils arranged in different strata in the stratum corneum.

Histologically, compact hyperkeratosis usually is noted, often with associated parakeratosis, epidermal atrophy with thinning or absence of the granular layer, and a bandlike lymphohistiocytic infiltrate in the papillary dermis.^1-3 Histopathologic differences between recent-onset versus longstanding lesions have been found, with old lesions lacking an inflammatory infiltrate.³ Furthermore, new lesions often show abnormalities in quantity and/or morphology of membrane-coating granules, also known as Odland bodies, in keratinocytes on electron microscopy,^3,10,17 while old lesions do not.³ Odland bodies are involved in normal desquamation, leading some to speculate on their role in HLP.¹⁰ Currently, it is unclear whether abnormalities in these organelles cause the retention hyperkeratosis seen in HLP or if such abnormalities are a secondary phenomenon.^3,17

There are questionable associations between HLP and diabetes mellitus type 2, hyperthyroidism, basal and squamous cell carcinomas of the skin, and gastrointestinal malignancy.^4,9,18 Our patient had a history of basal cell carcinoma on the face, diet-controlled diabetes mellitus, and hypothyroidism. Given the high prevalence of these diseases in the general population, however, it is difficult to ascertain whether a true association with HLP exists.

While HLP can slowly progress to involve additional body sites, it is overall a benign condition that does not require treatment. Therapeutic options are based on case reports, with no single treatment showing a consistent response. From review of the literature, therapies that have been most effective include dermabrasion, excision,¹⁹ topical 5-fluorouracil,^2,17,20 and oral retinoids.⁸ Hyperkeratosis lenticularis perstans generally is resistant to topical steroids, retinoids, and vitamin D₃ analogs, although success with betamethasone dipropionate,⁵ isotretinoin  
gel 0.05%,¹¹ and calcipotriol have been reported.⁶ A case of HLP with clinical response to psoralen plus UVA therapy also has been described.¹⁵

The antiviral drug brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, according to the drug’s developer, Chimerix.

Brincidofovir did not prevent clinically significant cytomegalovirus (CMV) infection through week 24 after hematopoietic stem cell transplant (HSCT).

However, the president and CEO of Chimerix said the company still believes there is a “viable path forward” for the drug.

Brincidofovir is an oral nucleotide analog that has shown in vitro antiviral activity against all 5 families of DNA viruses that affect humans, including herpes viruses and adenovirus.

The SUPPRESS trial, which was initiated in August 2013 and fully enrolled in June 2015, was informed by a successful phase 2 trial conducted in HSCT recipients.

The SUPPRESS trial enrolled and treated 452 adults who received allogeneic HSCTs from more than 40 transplant centers in the US, Canada, and Europe.

Subjects received twice-weekly brincidofovir or placebo (2:1 ratio) from the early post-transplant period through week 14 post-transplant, the period of highest risk for viral infections.

All patients in the trial were CMV-seropositive, placing them at high risk of CMV infection. The most common indications leading to HSCT were acute myelogenous leukemia (43% of patients), myelodysplasia (17%), non-Hodgkin lymphoma (10%), and acute lymphocytic leukemia (9%).

During the on-treatment period through week 14 after HSCT, fewer patients in the brincidofovir arm had a CMV infection, which was consistent with results from the phase 2 study of the drug.

However, during the 10 weeks off treatment from week 14 to week 24, there was an increase in CMV infections in the brincidofovir arm compared to the control arm. And there was a non-statistically significant increase in mortality in the brincidofovir arm compared to the control arm.

Preliminary analysis suggests the failure in preventing CMV infections and the increased mortality in the brincidofovir arm were driven by confirmed cases of graft-versus-host-disease (GVHD), which resulted in a significantly higher use of corticosteroids than in the control arm.

Both GVHD and the use of corticosteroids are risk factors for “late” CMV infection that occurs after the discontinuation of the antiviral in HSCT recipients.

The rate of study drug discontinuation for gastrointestinal events was less than 10% in this study, which is comparable to that observed in the phase 2 trial of brincidofovir in a similar HSCT population.

“While we are clearly disappointed in the top-line results from SUPPRESS, we remain committed to better understanding the full data set as we consider potential paths forward for brincidofovir,” said M. Michelle Berrey, MD, president and CEO of Chimerix.

“We will be evaluating the subgroups of patients within SUPPRESS, such as T-cell-depleted transplant recipients who have a lower risk of GVHD, to better understand these results and inform our next steps,” said W. Garrett Nichols, MD, Chimerix’s chief medical officer.

“We are reaching out to investigators and other experts to help us assess the complete data set to understand what may have caused the results of the SUPPRESS trial to differ substantially from those seen in the phase 2 study. Additionally, we are in communication with the US Food and Drug Administration and other regulatory bodies and will share any updates on the brincidofovir clinical program when we can.”

“With data currently in hand, we believe that brincidofovir may ultimately demonstrate a positive risk-benefit profile for the treatment of adenovirus and smallpox, as well as use in other populations in need of a novel compound for DNA viral infections.”

Chimerix plans to continue the programs testing brincidofovir in serious adenovirus infections and in smallpox. Pending the availability of complete data from SUPPRESS, including secondary endpoints in other dsDNA viral infections, Chimerix has elected to pause further enrollment in the phase 3 SUSTAIN and SURPASS trials in kidney transplant recipients.

A full analysis of the SUPPRESS trial results is ongoing. The data are scheduled to be presented at the BMT Tandem Meetings in Honolulu, Hawaii, in February.

The antiviral drug brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, according to the drug’s developer, Chimerix.

Brincidofovir did not prevent clinically significant cytomegalovirus (CMV) infection through week 24 after hematopoietic stem cell transplant (HSCT).

However, the president and CEO of Chimerix said the company still believes there is a “viable path forward” for the drug.

Brincidofovir is an oral nucleotide analog that has shown in vitro antiviral activity against all 5 families of DNA viruses that affect humans, including herpes viruses and adenovirus.

The SUPPRESS trial, which was initiated in August 2013 and fully enrolled in June 2015, was informed by a successful phase 2 trial conducted in HSCT recipients.

The SUPPRESS trial enrolled and treated 452 adults who received allogeneic HSCTs from more than 40 transplant centers in the US, Canada, and Europe.

Subjects received twice-weekly brincidofovir or placebo (2:1 ratio) from the early post-transplant period through week 14 post-transplant, the period of highest risk for viral infections.

All patients in the trial were CMV-seropositive, placing them at high risk of CMV infection. The most common indications leading to HSCT were acute myelogenous leukemia (43% of patients), myelodysplasia (17%), non-Hodgkin lymphoma (10%), and acute lymphocytic leukemia (9%).

During the on-treatment period through week 14 after HSCT, fewer patients in the brincidofovir arm had a CMV infection, which was consistent with results from the phase 2 study of the drug.

However, during the 10 weeks off treatment from week 14 to week 24, there was an increase in CMV infections in the brincidofovir arm compared to the control arm. And there was a non-statistically significant increase in mortality in the brincidofovir arm compared to the control arm.

Preliminary analysis suggests the failure in preventing CMV infections and the increased mortality in the brincidofovir arm were driven by confirmed cases of graft-versus-host-disease (GVHD), which resulted in a significantly higher use of corticosteroids than in the control arm.

Both GVHD and the use of corticosteroids are risk factors for “late” CMV infection that occurs after the discontinuation of the antiviral in HSCT recipients.

The rate of study drug discontinuation for gastrointestinal events was less than 10% in this study, which is comparable to that observed in the phase 2 trial of brincidofovir in a similar HSCT population.

“While we are clearly disappointed in the top-line results from SUPPRESS, we remain committed to better understanding the full data set as we consider potential paths forward for brincidofovir,” said M. Michelle Berrey, MD, president and CEO of Chimerix.

“We will be evaluating the subgroups of patients within SUPPRESS, such as T-cell-depleted transplant recipients who have a lower risk of GVHD, to better understand these results and inform our next steps,” said W. Garrett Nichols, MD, Chimerix’s chief medical officer.

“We are reaching out to investigators and other experts to help us assess the complete data set to understand what may have caused the results of the SUPPRESS trial to differ substantially from those seen in the phase 2 study. Additionally, we are in communication with the US Food and Drug Administration and other regulatory bodies and will share any updates on the brincidofovir clinical program when we can.”

“With data currently in hand, we believe that brincidofovir may ultimately demonstrate a positive risk-benefit profile for the treatment of adenovirus and smallpox, as well as use in other populations in need of a novel compound for DNA viral infections.”

Chimerix plans to continue the programs testing brincidofovir in serious adenovirus infections and in smallpox. Pending the availability of complete data from SUPPRESS, including secondary endpoints in other dsDNA viral infections, Chimerix has elected to pause further enrollment in the phase 3 SUSTAIN and SURPASS trials in kidney transplant recipients.

A full analysis of the SUPPRESS trial results is ongoing. The data are scheduled to be presented at the BMT Tandem Meetings in Honolulu, Hawaii, in February.

The antiviral drug brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, according to the drug’s developer, Chimerix.

Brincidofovir did not prevent clinically significant cytomegalovirus (CMV) infection through week 24 after hematopoietic stem cell transplant (HSCT).

However, the president and CEO of Chimerix said the company still believes there is a “viable path forward” for the drug.

Brincidofovir is an oral nucleotide analog that has shown in vitro antiviral activity against all 5 families of DNA viruses that affect humans, including herpes viruses and adenovirus.

The SUPPRESS trial, which was initiated in August 2013 and fully enrolled in June 2015, was informed by a successful phase 2 trial conducted in HSCT recipients.

The SUPPRESS trial enrolled and treated 452 adults who received allogeneic HSCTs from more than 40 transplant centers in the US, Canada, and Europe.

Subjects received twice-weekly brincidofovir or placebo (2:1 ratio) from the early post-transplant period through week 14 post-transplant, the period of highest risk for viral infections.

All patients in the trial were CMV-seropositive, placing them at high risk of CMV infection. The most common indications leading to HSCT were acute myelogenous leukemia (43% of patients), myelodysplasia (17%), non-Hodgkin lymphoma (10%), and acute lymphocytic leukemia (9%).

During the on-treatment period through week 14 after HSCT, fewer patients in the brincidofovir arm had a CMV infection, which was consistent with results from the phase 2 study of the drug.

However, during the 10 weeks off treatment from week 14 to week 24, there was an increase in CMV infections in the brincidofovir arm compared to the control arm. And there was a non-statistically significant increase in mortality in the brincidofovir arm compared to the control arm.

Preliminary analysis suggests the failure in preventing CMV infections and the increased mortality in the brincidofovir arm were driven by confirmed cases of graft-versus-host-disease (GVHD), which resulted in a significantly higher use of corticosteroids than in the control arm.

Both GVHD and the use of corticosteroids are risk factors for “late” CMV infection that occurs after the discontinuation of the antiviral in HSCT recipients.

The rate of study drug discontinuation for gastrointestinal events was less than 10% in this study, which is comparable to that observed in the phase 2 trial of brincidofovir in a similar HSCT population.

“While we are clearly disappointed in the top-line results from SUPPRESS, we remain committed to better understanding the full data set as we consider potential paths forward for brincidofovir,” said M. Michelle Berrey, MD, president and CEO of Chimerix.

“We will be evaluating the subgroups of patients within SUPPRESS, such as T-cell-depleted transplant recipients who have a lower risk of GVHD, to better understand these results and inform our next steps,” said W. Garrett Nichols, MD, Chimerix’s chief medical officer.

“We are reaching out to investigators and other experts to help us assess the complete data set to understand what may have caused the results of the SUPPRESS trial to differ substantially from those seen in the phase 2 study. Additionally, we are in communication with the US Food and Drug Administration and other regulatory bodies and will share any updates on the brincidofovir clinical program when we can.”

“With data currently in hand, we believe that brincidofovir may ultimately demonstrate a positive risk-benefit profile for the treatment of adenovirus and smallpox, as well as use in other populations in need of a novel compound for DNA viral infections.”

Chimerix plans to continue the programs testing brincidofovir in serious adenovirus infections and in smallpox. Pending the availability of complete data from SUPPRESS, including secondary endpoints in other dsDNA viral infections, Chimerix has elected to pause further enrollment in the phase 3 SUSTAIN and SURPASS trials in kidney transplant recipients.

A full analysis of the SUPPRESS trial results is ongoing. The data are scheduled to be presented at the BMT Tandem Meetings in Honolulu, Hawaii, in February.