In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.

As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.

First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
 

Size Matters

My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.

What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.

A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.

On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.

Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.

As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.

First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
 

Size Matters

My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.

What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.

A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.

On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.

Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In my last column, I began to explore the factors affecting the compensation of primary care providers (PCPs). I described two apparent economic paradoxes. First, while most healthcare systems consider their primary care segments as loss leaders, they continue to seek and hire more PCPs. The second is while PCPs are in short supply, most of them feel that they are underpaid. Supply and demand doesn’t seem to be making them more valuable in the economic sense. The explanations for these nonintuitive observations are first, healthcare systems need the volume of patients stored in the practices of even unprofitable primary care physicians to feed the high-profit specialties in their businesses. Second, there is a limit to how large a gap between revenue and overhead the systems can accept for their primary care practices. Not surprisingly, this means that system administrators must continue to nudge those PCP practices closer toward profitability, usually by demanding higher productivity.

As I did in my last letter, I will continue to lean on a discussion for PCP compensation by a large international management consulting firm I found on the internet. I am not condoning the consultant’s advice, but merely using it as a scaffolding on which to hang the rather squishy topics of time, clinical quality, and patient satisfaction. I only intend to ask questions, and I promise no answers.

First, let me make it clear that I am defining PCPs as providers who are on a performance-based pathway, which is by far the most prevalent model. A fixed-salary arrangement hasn’t made sense to me since I was a 17-year-old lifeguard paid by the hour for sitting by a pool. Had I been paid by the rescue, I would have finished the summer empty handed. A fixed salary provided me a sense of security, but it offered no path for advancement and was boring as hell. The primary care provider I am talking about has an interest in developing relationships with his/her patients, building a practice, and offering some degree of continuity. In other words, I am not considering providers working in walk-in clinics as PCPs.
 

Size Matters

My high-powered management consultant is recommending to his healthcare system management clients that they emphasize panel size component as they craft their compensation packages for PCPs. Maybe even to the point of giving it more weight than the productivity piece. This, of course, makes perfect business sense if the primary value of a PCP to the system lies in the patients he/she brings into the system.

What does this emphasis on size mean for you as a provider? If your boss is following my consultant’s advice, then you would want to be growing your panel size to improve your compensation. You could do this by a marketing plan that makes you more popular. But, I can hear you muttering that you never wanted to be a contestant in a popularity contest. Although I must say that historically this was a fact of life in any community when new providers came to town.

A provider can choose his/her own definition of popularity. You can let it be known that you are a liberal prescription writer and fill your practice with drug-seeking patients. Or you could promote customer-friendly schedules and behaviors in your office staff. And, of course, you can simply exude an aura of caring, which has always been an effective practice-building tool.

On the other hand, you may believe that you have more patients than you can handle. You may fear that growing your practice runs the risk of putting the quality of your patients’ care and your own physical and mental health at risk.

Theoretically, you could keep your panel size unchanged and increase your productivity to enhance your value and therefore your compensation. In the next part of this miniseries we’ll look at the stumbling blocks that can make increasing productivity difficult.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.

That’s a lot.

Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.

In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.

When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.

Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.

I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).

But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.

Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.

That’s worth more than $4.80 per year.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.

That’s a lot.

Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.

In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.

When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.

Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.

I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).

But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.

Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.

That’s worth more than $4.80 per year.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

A recent review of the Open Payments database found that, over the last 10 years, the evil forces of Big Pharma have paid doctors $12.1 billion dollars.

That’s a lot.

Of course, there are also quite a few doctors out there, and the word “paid” is kind of a misnomer. Yes, some people did get paid directly — cash for research, speaking engagements, teaching other docs — but a lot of the money was really spent on marketing. It may show that Dr. Jones was “paid” $200 one day, when in reality that was the cost of providing lunch to her, her five-person office staff, and the medical student following her around that afternoon.

In the last 10 years, I’ve accepted “payments” of one pizza and three iced coffees, so I guess I’m on there, too.

When you actually break it down, this comes out to a national average of (drum roll) $48 per doctor over 10 years.

Let’s face it, if your prescribing habits can be bought for $4.80 a year ... that’s pretty sad. They say everyone has their price, but hopefully it’s not that of a Happy Meal.

I understand the reasons for tracking this sort of thing. The system certainly can be — and has been — gamed for abuse. If one doctor is getting a ridiculous amount of money for doing nothing but writing scripts for Walletgouge-XR, that certainly needs to be known. Something is rotten in the state of Denmark (or wherever).

But the headline, especially when used in the lay media, makes it sound like all docs are on payola, and further erodes trust in the medical field. The fact that it works out to $4.80 per doctor each year is going to buried deeper in the article, by which time most readers will have moved on to see what Taylor Swift is up to.

Perhaps I’ve taken it to an extreme, but since the pizza (2014) I haven’t done lunch at my office. I still meet with reps, but they’re told now that I don’t do lunch, or bagels, or even iced coffee anymore. Tell me what I need to know about the new drug, but at this point in my career I’d rather have time. By not meeting a rep over lunch, or coffee, it adds 30-60 minutes to my day to use for reviewing tests, returning calls, and typing up notes. Those are things I’m going to have to do at some point, so I’d rather do them at my office and have the extra time at home, even if it’s just to do a jigsaw puzzle with my daughter.

That’s worth more than $4.80 per year.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An evolving legal landscape surrounding medication abortion has left physicians with as many questions as patients. A panel of clinicians at the annual meeting of the American College of Physicians offered guidance on how to help patients who choose medication abortion, which is available to women until 10 weeks of gestation.

Approved in 2000, abortion pills have become the most common method for terminating pregnancy in the United States, accounting for 63% of all abortions in 2023. The US Supreme Court is reviewing access to medication abortions, with a decision expected within months.

According to the Guttmacher Institute, 29 states as of February restrict access to medication abortion, either by limiting or banning the use of the drugs or by curtailing who can prescribe them and under what circumstances.
 

First, Determine Gestational Age

Cynthia Chuang, MD, MSc, an internist and professor of medicine at Penn State College of Medicine in Hershey, Pennsylvania, said in most cases, a woman can pinpoint the date of the first day of her last menstrual period, and the physician can confirm gestational age is 70 days or less. An ultrasound should be performed if the date of the last period is uncertain, she said, or if ectopic pregnancy is suspected, periods are irregular, or ultrasound is legally required in the state.

Women are not eligible for abortion pills if they have a bleeding or clotting disorder, have an intrauterine device, have adrenal insufficiency or chronic steroid use, or have porphyria or hemoglobin levels < 9 g/dL, she said.

“If the person has a known hemoglobin of less than 9, we would suggest that person have a procedural abortion,” Dr. Chuang said.
 

Components of Medication

Patients first receive 200 mg of oral mifepristone, which separates the pregnancy from the uterine wall. “Typically, people don’t experience side effects from the mifepristone alone,” Dr. Chaung said.

In the next 48 hours, the patient takes 800 mcg of misoprostol, either vaginally or buccally. “Patients can expect heavy cramping and bleeding 1-2 days after taking misoprostol,” she said. The bleeding should gradually subside over the following week or 2, she said. If the gestational age is 9 weeks or more, a second dose of misoprostol can be administered 3-6 hours after the first dose to improve efficacy.

If mifepristone is not available, misoprostol can be used alone in three doses spaced 3 hours apart, Dr. Chuang said.

The failure rate for mifepristone plus misoprostol has been calculated at 2% if the gestational age is less than 7 weeks. For misoprostol alone, the failure rate varies by the study, depending on gestational age and population analyzed, Dr. Chuang said. A 2023 meta-analysis in Contraception put the failure rate at 11%.
 

When to Call the Clinician

Dr. Chuang said clinicians should instruct women who have taken abortion pills to call the clinic if they are soaking through two sanitary pads an hour for more than 1 hour, if there is little to no bleeding, or if they think the medication isn’t working after taking the full regimen.

Mindy Sobota, MD, MS, an internist and associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, recommended a continuing medical education site for evidence-based guidance on how best to talk with women about medication abortions.

She also recommended physicians and patients consult the Plan C website for guidance on telehealth services and price information on receiving abortion pills by mail in every state. “It’s a very reliable and safe clearing house,” Dr. Sobota said.

Internists should let patients know that whatever their choices are around pregnancy, they are open to discussing those choices and helping them through the process, Dr. Sobota said, adding that she makes those statements in annual visits.

Alexandra Bachorik, MD, EdM, director of education in the Women’s Health Unit and assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, said patients in restrictive states who need financial help related to obtaining abortion services in a less restricted state can visit the National Network of Abortion Funds, which can help people with travel or housing expenses.

Facilitating access to a clinic in a less restrictive state may be helpful to people approaching a gestational age limit, she said.

Adelaide McClintock, MD, an internist and assistant professor of general internal medicine at the University of Washington School of Medicine in Seattle, Washington, noted that even clinicians who cannot legally prescribe abortion pills can support their patients by providing resources and counseling on options before, during, and after pregnancy. Those who live in restrictive states also can provide support to women who have traveled to less restrictive states for an abortion if they have postabortion complications, she said.

She recommended the Reproductive Health Access Project website for a comprehensive guide for evidence-based care and counseling patients about all choices in reproductive healthcare.

Panelists urged clinicians to get familiar with abortion-access resources and keep them at their fingertips in practice. Patient requests for the services are common, she noted, as “one in four women will have an abortion by the age of 45.”

Dr. Chuang, Dr. McClintock, Dr. Sobota, and Dr. Bachorik reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

Genetic predisposition likely directs intestinal disease location in pediatric Crohn’s disease (CD) — whether colon-predominant (C-CD) or small-bowel-predominant (SB-CD), a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.

Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.

Baylor College of Medicine

According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
 

CD cases

Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.

As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.

The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.

Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).

“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.

EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation. 

According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.

This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.

Genetic predisposition likely directs intestinal disease location in pediatric Crohn’s disease (CD) — whether colon-predominant (C-CD) or small-bowel-predominant (SB-CD), a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.

Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.

Baylor College of Medicine

According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
 

CD cases

Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.

As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.

The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.

Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).

“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.

EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation. 

According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.

This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.

Genetic predisposition likely directs intestinal disease location in pediatric Crohn’s disease (CD) — whether colon-predominant (C-CD) or small-bowel-predominant (SB-CD), a small analysis in Cellular and Molecular Gastroenterology and Hepatology suggests.

Richard Kellermayer, MD, PhD, professor of pediatrics in the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston, Texas, and colleagues compared the genetic makeup of patients based on their Crohn’s disease location — predominantly in the small bowel (L4) or predominantly in the colon (L2 and/or L3). They then generated bipartite networks of susceptibility genes to study the polygenic background of the disease subtypes. They hypothesize that such networks may govern where a patient develops Crohn’s disease.

Baylor College of Medicine

According to current understanding, as Dr. Kellermayer told GI & Hepatology News, most autoimmune disorders, CD included, develop in people with a genetic predisposition after serial environmental insults between conception and young adulthood. “As opposed to single-gene-associated genetic disorders, autoimmune diseases are linked to several hundred genes in which subtle anomalies can work in concert to predispose someone to a certain disorder,” he said. “We hope our findings will guide the development of personalized treatments based on the disease location at diagnosis to advance precision medicine.”
 

CD cases

Eight cases of SB-CD and 11 of C-CD met the inclusion criteria. Mean age at CD diagnosis was about 11 years for both subtypes, while 36.3% of patients with C-CD were female vs 25% of those with SB-CD. Ethnicity was 72.2% White in the C-CD group and 87.5% in the SB-CD group.

As to the main ileocolonic locations according to the Paris Classification of pediatric inflammatory bowel disease, 54.5% in the C-CD group had involvement at L2 and 45.5% at L3. In SB-CD cases, 100% had disease at L4b, 37.5% at L4, and 50% at L1.

The researchers identified 115 single-nucleotide polymorphisms (SNPs) with a combined annotation-dependent depletion (CADD) score on Phil’s Read Editor (PHRED) of >10 that was associated with 97 genes. PHRED is a computer program measuring the quality of the identification of nucleobases generated by automated DNA sequencing and scores the deleteriousness of single-nucleotide variants. The identified genes in this study had a significantly (P < .01) different allele variation between C-CD and SB-CD.

Among the top 28 candidates was an SNP in the EFNA3 gene with a CADD score > 20 for differentiating between the two phenotypically distinct CD groups. Furthermore, the EFNA3 rs17723260 (predicted to be deleterious) was found to have a significantly lower allele frequency (4.5%) in C-CD compared with its allele frequency of 37.5% in SB-CD (chi square P = .0097).

“This finding indicates that EFNA3 might play a role in modulating colonic inflammation, in which a deleterious genetic defect might provide protection against colitis (and direct autoimmunity against the proximal small bowel) in the polygenic background of CD,” the investigators wrote.

EFNA3 has been linked to both CD and ulcerative colitis. Another four genes associated with the top five SNP candidates had already been connected with IBD or mammalian intestinal inflammation. 

According to the authors, the biomedical literature and mouse model findings “implicate the translational relevance of our candidate gene compendium for directing colon- vs small-bowel–predominant CD development.” They hope the findings will be replicated in larger CD cohorts differentiated by disease location. “Our work may set the nidus for CD subtype–based precision medicine by guiding individualized treatment strategies,” they wrote.

This study was supported by the ProKIIDS Network of the Crohn’s and Colitis Foundation and the Public Health Service. It was also supported by the Wagner, Frugoni, and Klaasmeyer families’ Gutsy Kids Fund and by the DR and GL Laws Fund. The authors disclosed no conflicts of interest.