MDedge Dermatology

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Women with psoriatic arthritis (PsA) presented with more severe disease at baseline and were less likely to achieve favorable outcomes after 12 months of treatment with either ustekinumab (Stelara) or a tumor necrosis factor (TNF) inhibitor, compared with men, according to a post hoc analysis of data from nearly 1,000 individuals.

Although data suggest that the overall prevalence of PsA is similar across genders, recent studies have identified differences in various aspects of PsA between men and women, wrote Arno W.R. Van Kuijk, MD, of Amsterdam Rheumatology and Immunology Center, and colleagues wrote in a study published in Rheumatology.

“Accumulating evidence in multiple rheumatic diseases indicates that gender may influence the likelihood of achieving the desired outcome with treatment,” but studies of differences in treatment response according to gender are limited, they said.

The researchers conducted a post hoc analysis of women and men with PsA who were part of PsABio, a noninterventional European study of patients with PsA. All participants were starting first-, second-, or third-line treatment with ustekinumab or a TNF inhibitor. The primary outcome was response to treatment at 12 months. Disease activity was assessed using the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), the Health Assessment Questionnaire–Disability Index (HAQ-DI), and total score on the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire.

Baseline available data for 512 women and 417 men showed the mean duration of disease was similar between genders (6.7 years for females and 6.9 years for males); body mass index was similar, as was the proportion of male and female patients receiving concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Females scored significantly worse than males on disease activity assessments at baseline with mean cDAPSA scores of 32.3 and 26.8, respectively.

The final analysis of 895 patients with baseline data and a postbaseline assessment included 439 who started ustekinumab (247 females, 192 males), and 456 who started a TNF inhibitor (248 females, 208 males).

At 12 months, females showed smaller degrees of improvement than males; 57.8% and 80.3%, respectively, achieved low disease activity based on cDAPSA scores, while 33.7% and 55.5% of females and males, respectively, achieved minimal disease activity. Measures of disability were higher in females than males, with HAQ-DI scores of 0.85 versus 0.50. PsAID-12 scores also were higher for females, compared with males (3.5 vs. 2.4).

A total of 81.7% of patients were on their initial biologic DMARD after 12 months, but more females than males who were taking ustekinumab or a TNF inhibitor changed or discontinued treatment.

Treatment persistence was significantly lower in females than males (P = .01), and lack of effectiveness was the main reason for discontinuation regardless of gender.

“The analysis of gender subgroup results of the PsABio study has expanded previously published observations that men and women with PsA have different experiences with the disease activity, clinical manifestations, impact on health-related quality of life, response to [biologic] DMARDs, and drug persistence,” the researchers wrote.

The lack of a medication protocol in the PsABio study limited the conclusions that could be drawn from the post hoc analysis, but the results were strengthened by the relatively large and diverse sample size and the inclusion of responses to more than one medication, the researchers noted.

The study was supported by Janssen. Dr. Van Kuijk disclosed serving as a consultant and receiving grant support from Janssen and other companies; several coauthors also disclosed relationships with Janssen.

Into thin, but healthy, air

Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.

pxfuel

All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.

Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.

To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.

While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.

This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.

Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
 

Sleep survey: The restless majority

Newsflash! This just in: Nobody is sleeping well.

When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.

klebercordeiro/Getty Images

Not surprised. So what’s keeping us up?

Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.

Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.

The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.

Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
 

Seen a UFO recently? Don’t blame COVID

First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.

Jat AM/Pixabay

The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?

If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.

The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.

That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.

Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.

See? That’s fabrication. We made that up.

This article was updated 5/15/23.

Into thin, but healthy, air

Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.

pxfuel

All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.

Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.

To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.

While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.

This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.

Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
 

Sleep survey: The restless majority

Newsflash! This just in: Nobody is sleeping well.

When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.

klebercordeiro/Getty Images

Not surprised. So what’s keeping us up?

Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.

Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.

The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.

Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
 

Seen a UFO recently? Don’t blame COVID

First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.

Jat AM/Pixabay

The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?

If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.

The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.

That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.

Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.

See? That’s fabrication. We made that up.

This article was updated 5/15/23.

Into thin, but healthy, air

Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.

pxfuel

All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.

Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.

To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.

While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.

This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.

Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
 

Sleep survey: The restless majority

Newsflash! This just in: Nobody is sleeping well.

When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.

klebercordeiro/Getty Images

Not surprised. So what’s keeping us up?

Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.

Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.

The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.

Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
 

Seen a UFO recently? Don’t blame COVID

First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.

Jat AM/Pixabay

The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?

If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.

The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.

That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.

Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.

See? That’s fabrication. We made that up.

This article was updated 5/15/23.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

Generalized essential telangiectasia (GET) is a rare, benign, and progressive primary cutaneous disease manifesting as telangiectases of the skin without systemic symptoms. It is unique in that it has widespread distribution on the body. Generalized essential telangiectasia more commonly affects women, usually in the fourth decade of life. The telangiectases most frequently appear on the legs, advancing over time to involve the trunk and arms and presenting in several patterns, including diffuse, macular, plaquelike, discrete, or confluent. Although GET typically is asymptomatic, numbness, tingling, and burning of the involved areas have been reported.¹ Treatment modalities for GET vary, though pulsed dye laser (PDL) therapy is most common. We report the case of a 40-year-old woman with a 5-year history of GET who was treated successfully with PDL.

A 40-year-old woman presented to our dermatology clinic with progressive prominence of blood vessels involving the dorsal aspects of the feet of 5 years’ duration. The prominent vessels had spread to involve the legs (Figure 1), buttocks, lower abdomen, forearms, and medial upper arms. The patient denied any personal history of bleeding disorders or family history of inherited conditions associated with visceral vascular malformations, such as hereditary hemorrhagic telangiectasia. Notably, magnetic resonance imaging of the liver approximately 3 weeks prior to initiating treatment with PDL demonstrated multiple hepatic lesions consistent with hemangiomas. The patient reported an occasional tingling sensation in the feet. She was otherwise asymptomatic but did report psychological distress associated with the skin changes.

Punch biopsies from the right lower leg and right buttock demonstrated increased vascularity of the dermis, a mild superficial perivascular lymphocytic infiltrate, and mild edema of the upper dermis without evidence of vasculitis. Autoimmune and coagulopathy workups were negative. The clinical and pathological findings were most consistent with GET.

Over the next 2.5 years, the patient underwent treatment with doxycycline and a series of 16 treatments with PDL (fluence, 6–12 J/cm²; pulse width, 10 milliseconds) with a positive cosmetic response. Considerable improvement in the lower legs was noted after 2 years of treatment with PDL (Figure 2).

Recurrence of GET was noted between PDL treatments, which led to progression of the disease process; all treated sites showed slow recurrence of lesions within several months after treatment. After 2 years, doxycycline was discontinued because of a perceived lack of continued benefit and the patient’s desire for alternative therapy. She was started on a 3-month trial of supplementation with ascorbic acid and rutin (or rutoside, a bioflavinoid), without noticeable improvement.

The diffuse distribution of dramatic telangiectases in GET makes treatment difficult. Standard treatments are not well established or studied due to the rarity of the condition. A review of PubMed articles indexed for MEDLINE using the terms treatment and generalized essential telangiectasias demonstrated several attempted treatment modalities for GET with varying success. In 4 cases in which PDL was used,^2-5 a positive cosmetic response was noted, similar to what was seen in our patient. In 1 of the 4 cases, conservative management with ascorbic acid and compression stockings was unsuccessful; however, 6-mercaptopurine, used to treat that patient’s ulcerative colitis, incidentally resulted in resolution of GET.² In 2 cases, response was maintained at 1.5-year follow-up.^3,5 Two cases noted successful treatment with acyclovir,^6,7 and 2 more demonstrated successful treatment with systemic ketoconazole.^6,8 Some improvement was reported with oral doxycycline or tetracycline in 2 cases.^9,10 Sclerotherapy improved the cosmetic appearance of telangiectases in one patient but was unsustainable because of the pain associated with the procedure.¹¹ Nd:YAG laser therapy was effective in one case¹²; however, the patient experienced relapse at 6-month follow-up—similar to what we observed in our patient. Three patients treated with intense pulsed light therapy experienced results that were maintained at 2-year follow-up.¹³

Generalized essential telangiectasia generally is considered a skin-limited disease without systemic manifestations, but 2 reports^11,14 described its association with gastric antral vascular ectasia—known as watermelon stomach. Hepatic hemangiomas are the most common benign liver lesions; however, the findings on magnetic resonance imaging in our patient, in combination with the 2 reported cases of watermelon stomach, suggest that the vascular changes of GET might extend below the skin.

Of the cases we reviewed, our patient had the longest reported duration of PDL treatment and follow-up for GET in which a successful, albeit transient, response was demonstrated. Our review of the literature revealed other reports of success with PDL and intense pulsed light therapy; results were maintained in some patients, while disease relapsed in others. Further studies are needed to understand why results are maintained in some but not all patients.

Although the cost of PDL as a cosmetic procedure must be taken into consideration when planning treatment of GET, we conclude that it is a safe option that can be effective until other treatment options are established to control the disease.

To the Editor:

Generalized essential telangiectasia (GET) is a rare, benign, and progressive primary cutaneous disease manifesting as telangiectases of the skin without systemic symptoms. It is unique in that it has widespread distribution on the body. Generalized essential telangiectasia more commonly affects women, usually in the fourth decade of life. The telangiectases most frequently appear on the legs, advancing over time to involve the trunk and arms and presenting in several patterns, including diffuse, macular, plaquelike, discrete, or confluent. Although GET typically is asymptomatic, numbness, tingling, and burning of the involved areas have been reported.¹ Treatment modalities for GET vary, though pulsed dye laser (PDL) therapy is most common. We report the case of a 40-year-old woman with a 5-year history of GET who was treated successfully with PDL.

A 40-year-old woman presented to our dermatology clinic with progressive prominence of blood vessels involving the dorsal aspects of the feet of 5 years’ duration. The prominent vessels had spread to involve the legs (Figure 1), buttocks, lower abdomen, forearms, and medial upper arms. The patient denied any personal history of bleeding disorders or family history of inherited conditions associated with visceral vascular malformations, such as hereditary hemorrhagic telangiectasia. Notably, magnetic resonance imaging of the liver approximately 3 weeks prior to initiating treatment with PDL demonstrated multiple hepatic lesions consistent with hemangiomas. The patient reported an occasional tingling sensation in the feet. She was otherwise asymptomatic but did report psychological distress associated with the skin changes.

Punch biopsies from the right lower leg and right buttock demonstrated increased vascularity of the dermis, a mild superficial perivascular lymphocytic infiltrate, and mild edema of the upper dermis without evidence of vasculitis. Autoimmune and coagulopathy workups were negative. The clinical and pathological findings were most consistent with GET.

Over the next 2.5 years, the patient underwent treatment with doxycycline and a series of 16 treatments with PDL (fluence, 6–12 J/cm²; pulse width, 10 milliseconds) with a positive cosmetic response. Considerable improvement in the lower legs was noted after 2 years of treatment with PDL (Figure 2).

Recurrence of GET was noted between PDL treatments, which led to progression of the disease process; all treated sites showed slow recurrence of lesions within several months after treatment. After 2 years, doxycycline was discontinued because of a perceived lack of continued benefit and the patient’s desire for alternative therapy. She was started on a 3-month trial of supplementation with ascorbic acid and rutin (or rutoside, a bioflavinoid), without noticeable improvement.

The diffuse distribution of dramatic telangiectases in GET makes treatment difficult. Standard treatments are not well established or studied due to the rarity of the condition. A review of PubMed articles indexed for MEDLINE using the terms treatment and generalized essential telangiectasias demonstrated several attempted treatment modalities for GET with varying success. In 4 cases in which PDL was used,^2-5 a positive cosmetic response was noted, similar to what was seen in our patient. In 1 of the 4 cases, conservative management with ascorbic acid and compression stockings was unsuccessful; however, 6-mercaptopurine, used to treat that patient’s ulcerative colitis, incidentally resulted in resolution of GET.² In 2 cases, response was maintained at 1.5-year follow-up.^3,5 Two cases noted successful treatment with acyclovir,^6,7 and 2 more demonstrated successful treatment with systemic ketoconazole.^6,8 Some improvement was reported with oral doxycycline or tetracycline in 2 cases.^9,10 Sclerotherapy improved the cosmetic appearance of telangiectases in one patient but was unsustainable because of the pain associated with the procedure.¹¹ Nd:YAG laser therapy was effective in one case¹²; however, the patient experienced relapse at 6-month follow-up—similar to what we observed in our patient. Three patients treated with intense pulsed light therapy experienced results that were maintained at 2-year follow-up.¹³

Generalized essential telangiectasia generally is considered a skin-limited disease without systemic manifestations, but 2 reports^11,14 described its association with gastric antral vascular ectasia—known as watermelon stomach. Hepatic hemangiomas are the most common benign liver lesions; however, the findings on magnetic resonance imaging in our patient, in combination with the 2 reported cases of watermelon stomach, suggest that the vascular changes of GET might extend below the skin.

Of the cases we reviewed, our patient had the longest reported duration of PDL treatment and follow-up for GET in which a successful, albeit transient, response was demonstrated. Our review of the literature revealed other reports of success with PDL and intense pulsed light therapy; results were maintained in some patients, while disease relapsed in others. Further studies are needed to understand why results are maintained in some but not all patients.

Although the cost of PDL as a cosmetic procedure must be taken into consideration when planning treatment of GET, we conclude that it is a safe option that can be effective until other treatment options are established to control the disease.

To the Editor:

Generalized essential telangiectasia (GET) is a rare, benign, and progressive primary cutaneous disease manifesting as telangiectases of the skin without systemic symptoms. It is unique in that it has widespread distribution on the body. Generalized essential telangiectasia more commonly affects women, usually in the fourth decade of life. The telangiectases most frequently appear on the legs, advancing over time to involve the trunk and arms and presenting in several patterns, including diffuse, macular, plaquelike, discrete, or confluent. Although GET typically is asymptomatic, numbness, tingling, and burning of the involved areas have been reported.¹ Treatment modalities for GET vary, though pulsed dye laser (PDL) therapy is most common. We report the case of a 40-year-old woman with a 5-year history of GET who was treated successfully with PDL.

A 40-year-old woman presented to our dermatology clinic with progressive prominence of blood vessels involving the dorsal aspects of the feet of 5 years’ duration. The prominent vessels had spread to involve the legs (Figure 1), buttocks, lower abdomen, forearms, and medial upper arms. The patient denied any personal history of bleeding disorders or family history of inherited conditions associated with visceral vascular malformations, such as hereditary hemorrhagic telangiectasia. Notably, magnetic resonance imaging of the liver approximately 3 weeks prior to initiating treatment with PDL demonstrated multiple hepatic lesions consistent with hemangiomas. The patient reported an occasional tingling sensation in the feet. She was otherwise asymptomatic but did report psychological distress associated with the skin changes.

Punch biopsies from the right lower leg and right buttock demonstrated increased vascularity of the dermis, a mild superficial perivascular lymphocytic infiltrate, and mild edema of the upper dermis without evidence of vasculitis. Autoimmune and coagulopathy workups were negative. The clinical and pathological findings were most consistent with GET.

Over the next 2.5 years, the patient underwent treatment with doxycycline and a series of 16 treatments with PDL (fluence, 6–12 J/cm²; pulse width, 10 milliseconds) with a positive cosmetic response. Considerable improvement in the lower legs was noted after 2 years of treatment with PDL (Figure 2).

Recurrence of GET was noted between PDL treatments, which led to progression of the disease process; all treated sites showed slow recurrence of lesions within several months after treatment. After 2 years, doxycycline was discontinued because of a perceived lack of continued benefit and the patient’s desire for alternative therapy. She was started on a 3-month trial of supplementation with ascorbic acid and rutin (or rutoside, a bioflavinoid), without noticeable improvement.

The diffuse distribution of dramatic telangiectases in GET makes treatment difficult. Standard treatments are not well established or studied due to the rarity of the condition. A review of PubMed articles indexed for MEDLINE using the terms treatment and generalized essential telangiectasias demonstrated several attempted treatment modalities for GET with varying success. In 4 cases in which PDL was used,^2-5 a positive cosmetic response was noted, similar to what was seen in our patient. In 1 of the 4 cases, conservative management with ascorbic acid and compression stockings was unsuccessful; however, 6-mercaptopurine, used to treat that patient’s ulcerative colitis, incidentally resulted in resolution of GET.² In 2 cases, response was maintained at 1.5-year follow-up.^3,5 Two cases noted successful treatment with acyclovir,^6,7 and 2 more demonstrated successful treatment with systemic ketoconazole.^6,8 Some improvement was reported with oral doxycycline or tetracycline in 2 cases.^9,10 Sclerotherapy improved the cosmetic appearance of telangiectases in one patient but was unsustainable because of the pain associated with the procedure.¹¹ Nd:YAG laser therapy was effective in one case¹²; however, the patient experienced relapse at 6-month follow-up—similar to what we observed in our patient. Three patients treated with intense pulsed light therapy experienced results that were maintained at 2-year follow-up.¹³

Generalized essential telangiectasia generally is considered a skin-limited disease without systemic manifestations, but 2 reports^11,14 described its association with gastric antral vascular ectasia—known as watermelon stomach. Hepatic hemangiomas are the most common benign liver lesions; however, the findings on magnetic resonance imaging in our patient, in combination with the 2 reported cases of watermelon stomach, suggest that the vascular changes of GET might extend below the skin.

Of the cases we reviewed, our patient had the longest reported duration of PDL treatment and follow-up for GET in which a successful, albeit transient, response was demonstrated. Our review of the literature revealed other reports of success with PDL and intense pulsed light therapy; results were maintained in some patients, while disease relapsed in others. Further studies are needed to understand why results are maintained in some but not all patients.

Although the cost of PDL as a cosmetic procedure must be taken into consideration when planning treatment of GET, we conclude that it is a safe option that can be effective until other treatment options are established to control the disease.

Cases of a potentially deadly and increasingly treatment-resistant fungus called Candida auris have skyrocketed 200% since 2019, prompting the Centers for Disease Control and Prevention to issue a warning to health care facilities about the rising threat.

C. auris is a yeast that spreads easily from touching it on a surface like a countertop. It can also spread from person to person. It isn’t a threat to healthy people, but people in hospitals and nursing homes are at a heightened risk because they might have weakened immune systems or be using invasive medical devices that can introduce the fungus inside their bodies. When C. auris progresses to causing an infection that reaches the brain, blood, or lungs, more than one in three people die.

The worrying increase was detailed in the journal Annals of Internal Medicine. In 2021, cases reached a count of 3,270 with an active infection, and 7,413 cases showed the fungus was present but hadn’t caused an infection. Infection counts were up 95% over the previous year, and the fungus showed up on screenings three times as often. The number of cases resistant to medication also tripled.

The CDC called the figures “alarming,” noting that the fungus was only detected in the United States in 2016. 

“The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on health care and public health systems during the COVID-19 pandemic,” the CDC explained in a news release.

Another potential reason for the jump could be that screening for C. auris has simply increased and it’s being found more often because it’s being looked for more often. But researchers believe that, even with the increase in testing, the reported counts are underestimated. That’s because even though screening has increased, health care providers still aren’t looking for the presence of the fungus as often as the CDC would like.

“The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said study author Meghan Lyman, MD, a CDC epidemiologist in Atlanta, in a statement.

Cases of C. auris continued to rise in 2022, the CDC said. A map on the agency’s website of reported cases from 2022 shows it was found in more than half of U.S. states, with the highest counts occurring in California, Florida, Illinois, Nevada, New York, and Texas. The fungus is a problem worldwide and is listed among the most threatening treatment-resistant fungi by the World Health Organization.

The study authors concluded that screening capacity for the fungus needs to be expanded nationwide so that when C. auris is detected, measures can be taken to prevent its spread.

A version of this article originally appeared on WebMD.com.

Cases of a potentially deadly and increasingly treatment-resistant fungus called Candida auris have skyrocketed 200% since 2019, prompting the Centers for Disease Control and Prevention to issue a warning to health care facilities about the rising threat.

C. auris is a yeast that spreads easily from touching it on a surface like a countertop. It can also spread from person to person. It isn’t a threat to healthy people, but people in hospitals and nursing homes are at a heightened risk because they might have weakened immune systems or be using invasive medical devices that can introduce the fungus inside their bodies. When C. auris progresses to causing an infection that reaches the brain, blood, or lungs, more than one in three people die.

The worrying increase was detailed in the journal Annals of Internal Medicine. In 2021, cases reached a count of 3,270 with an active infection, and 7,413 cases showed the fungus was present but hadn’t caused an infection. Infection counts were up 95% over the previous year, and the fungus showed up on screenings three times as often. The number of cases resistant to medication also tripled.

The CDC called the figures “alarming,” noting that the fungus was only detected in the United States in 2016. 

“The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on health care and public health systems during the COVID-19 pandemic,” the CDC explained in a news release.

Another potential reason for the jump could be that screening for C. auris has simply increased and it’s being found more often because it’s being looked for more often. But researchers believe that, even with the increase in testing, the reported counts are underestimated. That’s because even though screening has increased, health care providers still aren’t looking for the presence of the fungus as often as the CDC would like.

“The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said study author Meghan Lyman, MD, a CDC epidemiologist in Atlanta, in a statement.

Cases of C. auris continued to rise in 2022, the CDC said. A map on the agency’s website of reported cases from 2022 shows it was found in more than half of U.S. states, with the highest counts occurring in California, Florida, Illinois, Nevada, New York, and Texas. The fungus is a problem worldwide and is listed among the most threatening treatment-resistant fungi by the World Health Organization.

The study authors concluded that screening capacity for the fungus needs to be expanded nationwide so that when C. auris is detected, measures can be taken to prevent its spread.

A version of this article originally appeared on WebMD.com.

Cases of a potentially deadly and increasingly treatment-resistant fungus called Candida auris have skyrocketed 200% since 2019, prompting the Centers for Disease Control and Prevention to issue a warning to health care facilities about the rising threat.

C. auris is a yeast that spreads easily from touching it on a surface like a countertop. It can also spread from person to person. It isn’t a threat to healthy people, but people in hospitals and nursing homes are at a heightened risk because they might have weakened immune systems or be using invasive medical devices that can introduce the fungus inside their bodies. When C. auris progresses to causing an infection that reaches the brain, blood, or lungs, more than one in three people die.

The worrying increase was detailed in the journal Annals of Internal Medicine. In 2021, cases reached a count of 3,270 with an active infection, and 7,413 cases showed the fungus was present but hadn’t caused an infection. Infection counts were up 95% over the previous year, and the fungus showed up on screenings three times as often. The number of cases resistant to medication also tripled.

The CDC called the figures “alarming,” noting that the fungus was only detected in the United States in 2016. 

“The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on health care and public health systems during the COVID-19 pandemic,” the CDC explained in a news release.

Another potential reason for the jump could be that screening for C. auris has simply increased and it’s being found more often because it’s being looked for more often. But researchers believe that, even with the increase in testing, the reported counts are underestimated. That’s because even though screening has increased, health care providers still aren’t looking for the presence of the fungus as often as the CDC would like.

“The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said study author Meghan Lyman, MD, a CDC epidemiologist in Atlanta, in a statement.

Cases of C. auris continued to rise in 2022, the CDC said. A map on the agency’s website of reported cases from 2022 shows it was found in more than half of U.S. states, with the highest counts occurring in California, Florida, Illinois, Nevada, New York, and Texas. The fungus is a problem worldwide and is listed among the most threatening treatment-resistant fungi by the World Health Organization.

The study authors concluded that screening capacity for the fungus needs to be expanded nationwide so that when C. auris is detected, measures can be taken to prevent its spread.

A version of this article originally appeared on WebMD.com.

Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.

Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”

Most of the fourth-year medical students this news organization has followed in the run-up to Match Day found success, including an international medical graduate who matched into his chosen specialty after multiple disappointments.

“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”

Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.

Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”

International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.

Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.

Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.

The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.

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

Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.

Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”

Most of the fourth-year medical students this news organization has followed in the run-up to Match Day found success, including an international medical graduate who matched into his chosen specialty after multiple disappointments.

“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”

Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.

Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”

International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.

Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.

Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.

The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.

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

Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.

Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”

Most of the fourth-year medical students this news organization has followed in the run-up to Match Day found success, including an international medical graduate who matched into his chosen specialty after multiple disappointments.

“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”

Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.

Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”

International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.

Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.

Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.

The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.

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

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

NEW ORLEANS – Nemolizumab monotherapy for 16 weeks improved itch, skin lesions, and sleep disturbances in adults with prurigo nodularis (PN), results from a phase 3 trial demonstrated.

Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.

OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.

After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.

Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.

Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
 

Primary, secondary endpoint results

Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).

As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
 

Adverse events

Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.

The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.

“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”

Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”

Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.

As chair of the Arkansas State Medical Board, Brian T. Hyatt, MD, often sat in judgment of other physicians. Now, state officials are investigating the psychiatrist for alleged Medicaid fraud. He has stepped down as board chair, and state officials have suspended all Medicaid payments to Dr. Hyatt and his practice, Pinnacle Premier Psychiatry in Rogers, Arkansas.

Dr. Hyatt billed 99.95% of the claims for his patients’ hospital care to Medicaid at the highest severity level, according to an affidavit filed by an investigator with the Medicaid Fraud Control Unit, Arkansas Attorney General’s Office. Other Arkansas psychiatrists billed that same level in only about 39% of claims, the affidavit states.

The possible upcoding alleged in the affidavit was a red flag that prompted the state to temporarily suspend Dr. Hyatt’s Medicaid payments.

Dr. Hyatt has until this Friday to file an appeal. He did not respond to requests from this news organization for comment.

The affidavit pointed to other concerns. For example, a whistleblower who worked at the Northwest Medical Center where Dr. Hyatt admitted patients claimed that Dr. Hyatt was only on the floor a few minutes a day and that he had no contact with patients. A review of hundreds of hours of video by state investigators revealed that Dr. Hyatt did not enter patients’ rooms, nor did he have any contact with patients, according to the affidavit. Dr. Hyatt served as the hospital’s behavioral unit director from 2018 until his contract was abruptly terminated in May 2022, according to the affidavit.

However, Dr. Hyatt claimed to have conducted daily face-to-face evaluation and management with patients, according to the affidavit. In addition, the whistleblower claimed that Dr. Hyatt did not want patients to know his name and instructed staff to cover up his name on patient armbands.
 

Detaining patients

Dr. Hyatt also faces accusations that he held patients against their will, according to civil lawsuits filed in Washington County, Ark., reports the Arkansas Advocate. 

Karla Adrian-Caceres filed suit on Jan. 17. Ms. Adrian-Caceres also named Brooke Green, Northwest Arkansas Hospitals, and 25 unidentified hospital employees as defendants.

According to the complaint, Ms. Adrian-Caceres, an engineering student at the University of Arkansas, arrived at the Northwest Medical Emergency Department after accidentally taking too many Tylenol on Jan. 18, 2022. She was then taken by ambulance to a Northwest psychiatric facility in Springdale, court records show.

According to the complaint, Ms. Adrian-Caceres said that she was given a sedative and asked to sign consent for admission while on the way to Northwest. She said that she “signed some documents without being able to read or understand them at the time.”

When she asked when she could go home, Ms. Adrian-Caceres said, “more than one employee told her there was a minimum stay and that if she asked to leave, they would take her to court where a judge would give her a longer stay because the judge always sides with Dr. Hyatt and Northwest,” according to court documents. Northwest employees stripped Ms. Adrian-Caceres, searched her body, took all of her possessions from her and issued underwear and a uniform, according to the lawsuit.

Ms. Adrian-Caceres’ mother, Katty Caceres, claimed in the lawsuit that she was prohibited from seeing her daughter. Ms. Caceres spoke with five different employees, four of whom had only their first names on their badges. Each of them reportedly said that they could not help, or that the plaintiff “would be in there for some time” and that it was Dr. Hyatt’s decision regarding how long that would be, according to court documents.

Katty Caceres hired a local attorney named Aaron Cash to represent her daughter. On Jan. 20, 2022, Mr. Cash faxed a letter to the hospital demanding her release. When Ms. Caceres arrived to pick up her daughter, she claimed that staff members indicated that the daughter was there voluntarily and refused to release her “at the direction of Dr Hyatt.” During a phone call later that day, the plaintiff told her mother that her status was being changed to an involuntary hold, court documents show.

“At one point she was threatened with the longer time in there if she kept asking to leave,” Mr. Cash told this news organization. In addition, staff members reportedly told Ms. Adrian-Caceres that the “judge always sided with Dr Hyatt” and she “would get way longer there, 30-45 days if [she] went before the judge,” according to Mr. Cash.

Mr. Cash said nine other patients have contacted his firm with similar allegations against Dr. Hyatt.

“We’ve talked to many people that have experienced the same threats,” Mr. Cash said. “When they’re asking to leave, they get these threats, they get coerced … and they’re never taken to court. They’re never given opportunity to talk to a judge or to have a public defender appointed.”
 

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

As chair of the Arkansas State Medical Board, Brian T. Hyatt, MD, often sat in judgment of other physicians. Now, state officials are investigating the psychiatrist for alleged Medicaid fraud. He has stepped down as board chair, and state officials have suspended all Medicaid payments to Dr. Hyatt and his practice, Pinnacle Premier Psychiatry in Rogers, Arkansas.

Dr. Hyatt billed 99.95% of the claims for his patients’ hospital care to Medicaid at the highest severity level, according to an affidavit filed by an investigator with the Medicaid Fraud Control Unit, Arkansas Attorney General’s Office. Other Arkansas psychiatrists billed that same level in only about 39% of claims, the affidavit states.

The possible upcoding alleged in the affidavit was a red flag that prompted the state to temporarily suspend Dr. Hyatt’s Medicaid payments.

Dr. Hyatt has until this Friday to file an appeal. He did not respond to requests from this news organization for comment.

The affidavit pointed to other concerns. For example, a whistleblower who worked at the Northwest Medical Center where Dr. Hyatt admitted patients claimed that Dr. Hyatt was only on the floor a few minutes a day and that he had no contact with patients. A review of hundreds of hours of video by state investigators revealed that Dr. Hyatt did not enter patients’ rooms, nor did he have any contact with patients, according to the affidavit. Dr. Hyatt served as the hospital’s behavioral unit director from 2018 until his contract was abruptly terminated in May 2022, according to the affidavit.

However, Dr. Hyatt claimed to have conducted daily face-to-face evaluation and management with patients, according to the affidavit. In addition, the whistleblower claimed that Dr. Hyatt did not want patients to know his name and instructed staff to cover up his name on patient armbands.
 

Detaining patients

Dr. Hyatt also faces accusations that he held patients against their will, according to civil lawsuits filed in Washington County, Ark., reports the Arkansas Advocate. 

Karla Adrian-Caceres filed suit on Jan. 17. Ms. Adrian-Caceres also named Brooke Green, Northwest Arkansas Hospitals, and 25 unidentified hospital employees as defendants.

According to the complaint, Ms. Adrian-Caceres, an engineering student at the University of Arkansas, arrived at the Northwest Medical Emergency Department after accidentally taking too many Tylenol on Jan. 18, 2022. She was then taken by ambulance to a Northwest psychiatric facility in Springdale, court records show.

According to the complaint, Ms. Adrian-Caceres said that she was given a sedative and asked to sign consent for admission while on the way to Northwest. She said that she “signed some documents without being able to read or understand them at the time.”

When she asked when she could go home, Ms. Adrian-Caceres said, “more than one employee told her there was a minimum stay and that if she asked to leave, they would take her to court where a judge would give her a longer stay because the judge always sides with Dr. Hyatt and Northwest,” according to court documents. Northwest employees stripped Ms. Adrian-Caceres, searched her body, took all of her possessions from her and issued underwear and a uniform, according to the lawsuit.

Ms. Adrian-Caceres’ mother, Katty Caceres, claimed in the lawsuit that she was prohibited from seeing her daughter. Ms. Caceres spoke with five different employees, four of whom had only their first names on their badges. Each of them reportedly said that they could not help, or that the plaintiff “would be in there for some time” and that it was Dr. Hyatt’s decision regarding how long that would be, according to court documents.

Katty Caceres hired a local attorney named Aaron Cash to represent her daughter. On Jan. 20, 2022, Mr. Cash faxed a letter to the hospital demanding her release. When Ms. Caceres arrived to pick up her daughter, she claimed that staff members indicated that the daughter was there voluntarily and refused to release her “at the direction of Dr Hyatt.” During a phone call later that day, the plaintiff told her mother that her status was being changed to an involuntary hold, court documents show.

“At one point she was threatened with the longer time in there if she kept asking to leave,” Mr. Cash told this news organization. In addition, staff members reportedly told Ms. Adrian-Caceres that the “judge always sided with Dr Hyatt” and she “would get way longer there, 30-45 days if [she] went before the judge,” according to Mr. Cash.

Mr. Cash said nine other patients have contacted his firm with similar allegations against Dr. Hyatt.

“We’ve talked to many people that have experienced the same threats,” Mr. Cash said. “When they’re asking to leave, they get these threats, they get coerced … and they’re never taken to court. They’re never given opportunity to talk to a judge or to have a public defender appointed.”
 

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

As chair of the Arkansas State Medical Board, Brian T. Hyatt, MD, often sat in judgment of other physicians. Now, state officials are investigating the psychiatrist for alleged Medicaid fraud. He has stepped down as board chair, and state officials have suspended all Medicaid payments to Dr. Hyatt and his practice, Pinnacle Premier Psychiatry in Rogers, Arkansas.

Dr. Hyatt billed 99.95% of the claims for his patients’ hospital care to Medicaid at the highest severity level, according to an affidavit filed by an investigator with the Medicaid Fraud Control Unit, Arkansas Attorney General’s Office. Other Arkansas psychiatrists billed that same level in only about 39% of claims, the affidavit states.

The possible upcoding alleged in the affidavit was a red flag that prompted the state to temporarily suspend Dr. Hyatt’s Medicaid payments.

Dr. Hyatt has until this Friday to file an appeal. He did not respond to requests from this news organization for comment.

The affidavit pointed to other concerns. For example, a whistleblower who worked at the Northwest Medical Center where Dr. Hyatt admitted patients claimed that Dr. Hyatt was only on the floor a few minutes a day and that he had no contact with patients. A review of hundreds of hours of video by state investigators revealed that Dr. Hyatt did not enter patients’ rooms, nor did he have any contact with patients, according to the affidavit. Dr. Hyatt served as the hospital’s behavioral unit director from 2018 until his contract was abruptly terminated in May 2022, according to the affidavit.

However, Dr. Hyatt claimed to have conducted daily face-to-face evaluation and management with patients, according to the affidavit. In addition, the whistleblower claimed that Dr. Hyatt did not want patients to know his name and instructed staff to cover up his name on patient armbands.
 

Detaining patients

Dr. Hyatt also faces accusations that he held patients against their will, according to civil lawsuits filed in Washington County, Ark., reports the Arkansas Advocate. 

Karla Adrian-Caceres filed suit on Jan. 17. Ms. Adrian-Caceres also named Brooke Green, Northwest Arkansas Hospitals, and 25 unidentified hospital employees as defendants.

According to the complaint, Ms. Adrian-Caceres, an engineering student at the University of Arkansas, arrived at the Northwest Medical Emergency Department after accidentally taking too many Tylenol on Jan. 18, 2022. She was then taken by ambulance to a Northwest psychiatric facility in Springdale, court records show.

According to the complaint, Ms. Adrian-Caceres said that she was given a sedative and asked to sign consent for admission while on the way to Northwest. She said that she “signed some documents without being able to read or understand them at the time.”

When she asked when she could go home, Ms. Adrian-Caceres said, “more than one employee told her there was a minimum stay and that if she asked to leave, they would take her to court where a judge would give her a longer stay because the judge always sides with Dr. Hyatt and Northwest,” according to court documents. Northwest employees stripped Ms. Adrian-Caceres, searched her body, took all of her possessions from her and issued underwear and a uniform, according to the lawsuit.

Ms. Adrian-Caceres’ mother, Katty Caceres, claimed in the lawsuit that she was prohibited from seeing her daughter. Ms. Caceres spoke with five different employees, four of whom had only their first names on their badges. Each of them reportedly said that they could not help, or that the plaintiff “would be in there for some time” and that it was Dr. Hyatt’s decision regarding how long that would be, according to court documents.

Katty Caceres hired a local attorney named Aaron Cash to represent her daughter. On Jan. 20, 2022, Mr. Cash faxed a letter to the hospital demanding her release. When Ms. Caceres arrived to pick up her daughter, she claimed that staff members indicated that the daughter was there voluntarily and refused to release her “at the direction of Dr Hyatt.” During a phone call later that day, the plaintiff told her mother that her status was being changed to an involuntary hold, court documents show.

“At one point she was threatened with the longer time in there if she kept asking to leave,” Mr. Cash told this news organization. In addition, staff members reportedly told Ms. Adrian-Caceres that the “judge always sided with Dr Hyatt” and she “would get way longer there, 30-45 days if [she] went before the judge,” according to Mr. Cash.

Mr. Cash said nine other patients have contacted his firm with similar allegations against Dr. Hyatt.

“We’ve talked to many people that have experienced the same threats,” Mr. Cash said. “When they’re asking to leave, they get these threats, they get coerced … and they’re never taken to court. They’re never given opportunity to talk to a judge or to have a public defender appointed.”
 

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

Almost three-quarters of adults living in the United States report having never tested for HIV according to a newly published study from the Centers for Disease Control and Prevention. The reasons are complex and could jeopardize goals of ending the AIDS epidemic by 2030.

Patients and doctors alike face system challenges, including stigma, confidentiality concerns, racism, and inequitable access. Yet doctors, public health authorities, and even some patients agree that testing does work: In 2022, 81% of people diagnosed with HIV were linked to care within 30 days. Moreover, many patients are aware of where and how they wish to be tested. So, what would it take to achieve what ostensibly should be the lowest hanging fruit in the HIV care continuum?

“We didn’t look at the reasons for not testing,” Marc Pitasi, MPH, CDC epidemiologist and coauthor of the CDC study said in an interview. But “we found that the majority of people prefer the test in a clinical setting, so that’s a huge important piece of the puzzle,” he said.

The “never-tested” populations (4,334 of 6,072) in the study were predominantly aged 18-29 years (79.7%) and 50 years plus (78.1%). A total of 48% of never-tested adults also indicated that they had engaged in past-year risky behaviors (that is, injection drug use, treated for a sexually transmitted disease, exchanged sex/drugs for money, engaged in condomless anal sex, or had more than four sex partners). However, the difference between never-tested adults who live in EHE (Ending the HIV Epidemic in the U.S.)–designated jurisdictions (comprising 50 areas and 7 U.S. states responsible for more than 50% of new HIV infections) and those residing in non-EHE areas was only about 5 percentage points (69.1% vs. 74.5%, respectively), underscoring the need for broader engagement.

“There’s definitely a lack of testing across the board,” explained Lina Rosengren-Hovee, MD, MPH, MS, an infectious disease epidemiologist at the University of North Carolina at Chapel Hill. “There are all sorts of biases on how we make decisions and how we stratify … and these heuristics that we have in our minds to identify who is at risk and who needs testing,” she said.

“If we just look at the need for HIV testing based on who is at risk, I think that we are always going to fall short.”
 

Conflicting priorities

Seventeen years have passed since the CDC recommended that HIV testing and screening be offered at least once to all people aged 13-64 years in a routine clinical setting, with an opt-out option and without a separate written consent. People at higher risk (sexually active gay, bisexual, and other men who have sex with men) should be rescreened at least annually.

These recommendations were subsequently reinforced by numerous organizations, including the U.S. Preventive Services Task Force in 2013 and again in 2019, and the American Academy of Pediatrics in 2021.

But Dr. Rosengren-Hovee said that some clinicians remain unaware of the guidelines; for others, they’re usually not top-of-mind because of conflicting priorities.

This is especially true of pediatricians, who, despite data demonstrating that adolescents account for roughly 21% of new HIV diagnoses, rarely recognize or take advantage of HIV-testing opportunities during routine clinical visits.

“Pediatricians want to do the right thing for their patients but at the same time, they want to do the right thing on so many different fronts,” said Sarah Wood, MD, of the University of Pennsylvania, Philadelphia, and attending physician of adolescent medicine at Children’s Hospital of Philadelphia.

Dr. Wood is coauthor of a study published in Implementation Science Communicationsexamining pediatrician perspectives on implementing HIV testing and prevention. Participants identified confidentiality and time constraints as the most important challenges across every step of their workflow, which in turn, influenced perceptions about patients’ perceived risks for acquiring HIV – perceptions that Dr. Wood believes can be overcome.

“We need to really push pediatricians (through guideline-making societies like AAP and USPSTF) that screening should be universal and not linked to sexual activity or pinned to behavior, so the offer of testing is a universal opt-out,” she said. Additionally, “we need to make it easier for pediatricians to order the test,” for example, “through an office rapid test … and a redesigned workflow that moves the conversation away from physicians and nurse practitioners to medical assistants.”

Dr. Wood also pointed out that any effort would require pediatricians and other types of providers to overcome discomfort around sexual health conversations, noting that, while pediatricians are ideally positioned to work with parents to do education around sexual health, training and impetus are needed.
 

A fractured system

A fractured, often ill-funded U.S. health care system might also be at play according to Scott Harris, MD, MPH, state health officer of the Alabama Department of Public Health in Montgomery, and Association of State and Territorial Health Officials’ Infectious Disease Policy Committee chair.

“There’s a general consensus among everyone in public health that [HIV testing] is an important issue that we’re not addressing as well as we’d like to,” he said.

Dr. Harris acknowledged that, while COVID diverted attention away from HIV, some states have prioritized HIV more than others.

“We don’t have a national public health program; we have a nationwide public health program,” he said. “Everyone’s different and has different responsibilities and authorities ... depending on where their funding streams come from.”

The White House recently announced that it proposed a measure in its Fiscal Year 2023 budget to increase funding for HIV a further $313 million to accelerate efforts to end HIV by 2030, also adding a mandatory program to increase preexposure prophylaxis (PrEP) access. Without congressional approval, the measures are doomed to fail, leaving many states without the proper tools to enhance existing programs, and further painting overworked clinicians into a corner.

For patients, the ramifications are even greater.

“The majority of folks [in the CDC study] that were not tested said that if they were to get tested, they’d prefer to do that within the context of their primary care setting,” said Justin C. Smith, MS, MPH, director of the Campaign to End AIDS, Positive Impact Health Centers; a behavioral scientist at Emory University’s Rollins School of Public Health in Atlanta; and a member of the Presidential Advisory Council on HIV/AIDS.

“When you create a more responsive system that really speaks to the needs that people are expressing, that can provide better outcomes,” Dr. Smith said.

“It’s vital that we create health care and public health interventions that change the dynamics ... and make sure that we’re designing systems with the people that we’re trying to serve at the center.”

Mr. Pitasi, Dr. Rosengren-Hovee, Dr. Wood, Dr. Harris, and Dr. Smith have disclosed no relevant financial relationships.

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

Almost three-quarters of adults living in the United States report having never tested for HIV according to a newly published study from the Centers for Disease Control and Prevention. The reasons are complex and could jeopardize goals of ending the AIDS epidemic by 2030.

Patients and doctors alike face system challenges, including stigma, confidentiality concerns, racism, and inequitable access. Yet doctors, public health authorities, and even some patients agree that testing does work: In 2022, 81% of people diagnosed with HIV were linked to care within 30 days. Moreover, many patients are aware of where and how they wish to be tested. So, what would it take to achieve what ostensibly should be the lowest hanging fruit in the HIV care continuum?

“We didn’t look at the reasons for not testing,” Marc Pitasi, MPH, CDC epidemiologist and coauthor of the CDC study said in an interview. But “we found that the majority of people prefer the test in a clinical setting, so that’s a huge important piece of the puzzle,” he said.

The “never-tested” populations (4,334 of 6,072) in the study were predominantly aged 18-29 years (79.7%) and 50 years plus (78.1%). A total of 48% of never-tested adults also indicated that they had engaged in past-year risky behaviors (that is, injection drug use, treated for a sexually transmitted disease, exchanged sex/drugs for money, engaged in condomless anal sex, or had more than four sex partners). However, the difference between never-tested adults who live in EHE (Ending the HIV Epidemic in the U.S.)–designated jurisdictions (comprising 50 areas and 7 U.S. states responsible for more than 50% of new HIV infections) and those residing in non-EHE areas was only about 5 percentage points (69.1% vs. 74.5%, respectively), underscoring the need for broader engagement.

“There’s definitely a lack of testing across the board,” explained Lina Rosengren-Hovee, MD, MPH, MS, an infectious disease epidemiologist at the University of North Carolina at Chapel Hill. “There are all sorts of biases on how we make decisions and how we stratify … and these heuristics that we have in our minds to identify who is at risk and who needs testing,” she said.

“If we just look at the need for HIV testing based on who is at risk, I think that we are always going to fall short.”
 

Conflicting priorities

Seventeen years have passed since the CDC recommended that HIV testing and screening be offered at least once to all people aged 13-64 years in a routine clinical setting, with an opt-out option and without a separate written consent. People at higher risk (sexually active gay, bisexual, and other men who have sex with men) should be rescreened at least annually.

These recommendations were subsequently reinforced by numerous organizations, including the U.S. Preventive Services Task Force in 2013 and again in 2019, and the American Academy of Pediatrics in 2021.

But Dr. Rosengren-Hovee said that some clinicians remain unaware of the guidelines; for others, they’re usually not top-of-mind because of conflicting priorities.

This is especially true of pediatricians, who, despite data demonstrating that adolescents account for roughly 21% of new HIV diagnoses, rarely recognize or take advantage of HIV-testing opportunities during routine clinical visits.

“Pediatricians want to do the right thing for their patients but at the same time, they want to do the right thing on so many different fronts,” said Sarah Wood, MD, of the University of Pennsylvania, Philadelphia, and attending physician of adolescent medicine at Children’s Hospital of Philadelphia.

Dr. Wood is coauthor of a study published in Implementation Science Communicationsexamining pediatrician perspectives on implementing HIV testing and prevention. Participants identified confidentiality and time constraints as the most important challenges across every step of their workflow, which in turn, influenced perceptions about patients’ perceived risks for acquiring HIV – perceptions that Dr. Wood believes can be overcome.

“We need to really push pediatricians (through guideline-making societies like AAP and USPSTF) that screening should be universal and not linked to sexual activity or pinned to behavior, so the offer of testing is a universal opt-out,” she said. Additionally, “we need to make it easier for pediatricians to order the test,” for example, “through an office rapid test … and a redesigned workflow that moves the conversation away from physicians and nurse practitioners to medical assistants.”

Dr. Wood also pointed out that any effort would require pediatricians and other types of providers to overcome discomfort around sexual health conversations, noting that, while pediatricians are ideally positioned to work with parents to do education around sexual health, training and impetus are needed.
 

A fractured system

A fractured, often ill-funded U.S. health care system might also be at play according to Scott Harris, MD, MPH, state health officer of the Alabama Department of Public Health in Montgomery, and Association of State and Territorial Health Officials’ Infectious Disease Policy Committee chair.

“There’s a general consensus among everyone in public health that [HIV testing] is an important issue that we’re not addressing as well as we’d like to,” he said.

Dr. Harris acknowledged that, while COVID diverted attention away from HIV, some states have prioritized HIV more than others.

“We don’t have a national public health program; we have a nationwide public health program,” he said. “Everyone’s different and has different responsibilities and authorities ... depending on where their funding streams come from.”

The White House recently announced that it proposed a measure in its Fiscal Year 2023 budget to increase funding for HIV a further $313 million to accelerate efforts to end HIV by 2030, also adding a mandatory program to increase preexposure prophylaxis (PrEP) access. Without congressional approval, the measures are doomed to fail, leaving many states without the proper tools to enhance existing programs, and further painting overworked clinicians into a corner.

For patients, the ramifications are even greater.

“The majority of folks [in the CDC study] that were not tested said that if they were to get tested, they’d prefer to do that within the context of their primary care setting,” said Justin C. Smith, MS, MPH, director of the Campaign to End AIDS, Positive Impact Health Centers; a behavioral scientist at Emory University’s Rollins School of Public Health in Atlanta; and a member of the Presidential Advisory Council on HIV/AIDS.

“When you create a more responsive system that really speaks to the needs that people are expressing, that can provide better outcomes,” Dr. Smith said.

“It’s vital that we create health care and public health interventions that change the dynamics ... and make sure that we’re designing systems with the people that we’re trying to serve at the center.”

Mr. Pitasi, Dr. Rosengren-Hovee, Dr. Wood, Dr. Harris, and Dr. Smith have disclosed no relevant financial relationships.

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

Almost three-quarters of adults living in the United States report having never tested for HIV according to a newly published study from the Centers for Disease Control and Prevention. The reasons are complex and could jeopardize goals of ending the AIDS epidemic by 2030.

Patients and doctors alike face system challenges, including stigma, confidentiality concerns, racism, and inequitable access. Yet doctors, public health authorities, and even some patients agree that testing does work: In 2022, 81% of people diagnosed with HIV were linked to care within 30 days. Moreover, many patients are aware of where and how they wish to be tested. So, what would it take to achieve what ostensibly should be the lowest hanging fruit in the HIV care continuum?

“We didn’t look at the reasons for not testing,” Marc Pitasi, MPH, CDC epidemiologist and coauthor of the CDC study said in an interview. But “we found that the majority of people prefer the test in a clinical setting, so that’s a huge important piece of the puzzle,” he said.

The “never-tested” populations (4,334 of 6,072) in the study were predominantly aged 18-29 years (79.7%) and 50 years plus (78.1%). A total of 48% of never-tested adults also indicated that they had engaged in past-year risky behaviors (that is, injection drug use, treated for a sexually transmitted disease, exchanged sex/drugs for money, engaged in condomless anal sex, or had more than four sex partners). However, the difference between never-tested adults who live in EHE (Ending the HIV Epidemic in the U.S.)–designated jurisdictions (comprising 50 areas and 7 U.S. states responsible for more than 50% of new HIV infections) and those residing in non-EHE areas was only about 5 percentage points (69.1% vs. 74.5%, respectively), underscoring the need for broader engagement.

“There’s definitely a lack of testing across the board,” explained Lina Rosengren-Hovee, MD, MPH, MS, an infectious disease epidemiologist at the University of North Carolina at Chapel Hill. “There are all sorts of biases on how we make decisions and how we stratify … and these heuristics that we have in our minds to identify who is at risk and who needs testing,” she said.

“If we just look at the need for HIV testing based on who is at risk, I think that we are always going to fall short.”
 

Conflicting priorities

Seventeen years have passed since the CDC recommended that HIV testing and screening be offered at least once to all people aged 13-64 years in a routine clinical setting, with an opt-out option and without a separate written consent. People at higher risk (sexually active gay, bisexual, and other men who have sex with men) should be rescreened at least annually.

These recommendations were subsequently reinforced by numerous organizations, including the U.S. Preventive Services Task Force in 2013 and again in 2019, and the American Academy of Pediatrics in 2021.

But Dr. Rosengren-Hovee said that some clinicians remain unaware of the guidelines; for others, they’re usually not top-of-mind because of conflicting priorities.

This is especially true of pediatricians, who, despite data demonstrating that adolescents account for roughly 21% of new HIV diagnoses, rarely recognize or take advantage of HIV-testing opportunities during routine clinical visits.

“Pediatricians want to do the right thing for their patients but at the same time, they want to do the right thing on so many different fronts,” said Sarah Wood, MD, of the University of Pennsylvania, Philadelphia, and attending physician of adolescent medicine at Children’s Hospital of Philadelphia.

Dr. Wood is coauthor of a study published in Implementation Science Communicationsexamining pediatrician perspectives on implementing HIV testing and prevention. Participants identified confidentiality and time constraints as the most important challenges across every step of their workflow, which in turn, influenced perceptions about patients’ perceived risks for acquiring HIV – perceptions that Dr. Wood believes can be overcome.

“We need to really push pediatricians (through guideline-making societies like AAP and USPSTF) that screening should be universal and not linked to sexual activity or pinned to behavior, so the offer of testing is a universal opt-out,” she said. Additionally, “we need to make it easier for pediatricians to order the test,” for example, “through an office rapid test … and a redesigned workflow that moves the conversation away from physicians and nurse practitioners to medical assistants.”

Dr. Wood also pointed out that any effort would require pediatricians and other types of providers to overcome discomfort around sexual health conversations, noting that, while pediatricians are ideally positioned to work with parents to do education around sexual health, training and impetus are needed.
 

A fractured system

A fractured, often ill-funded U.S. health care system might also be at play according to Scott Harris, MD, MPH, state health officer of the Alabama Department of Public Health in Montgomery, and Association of State and Territorial Health Officials’ Infectious Disease Policy Committee chair.

“There’s a general consensus among everyone in public health that [HIV testing] is an important issue that we’re not addressing as well as we’d like to,” he said.

Dr. Harris acknowledged that, while COVID diverted attention away from HIV, some states have prioritized HIV more than others.

“We don’t have a national public health program; we have a nationwide public health program,” he said. “Everyone’s different and has different responsibilities and authorities ... depending on where their funding streams come from.”

The White House recently announced that it proposed a measure in its Fiscal Year 2023 budget to increase funding for HIV a further $313 million to accelerate efforts to end HIV by 2030, also adding a mandatory program to increase preexposure prophylaxis (PrEP) access. Without congressional approval, the measures are doomed to fail, leaving many states without the proper tools to enhance existing programs, and further painting overworked clinicians into a corner.

For patients, the ramifications are even greater.

“The majority of folks [in the CDC study] that were not tested said that if they were to get tested, they’d prefer to do that within the context of their primary care setting,” said Justin C. Smith, MS, MPH, director of the Campaign to End AIDS, Positive Impact Health Centers; a behavioral scientist at Emory University’s Rollins School of Public Health in Atlanta; and a member of the Presidential Advisory Council on HIV/AIDS.

“When you create a more responsive system that really speaks to the needs that people are expressing, that can provide better outcomes,” Dr. Smith said.

“It’s vital that we create health care and public health interventions that change the dynamics ... and make sure that we’re designing systems with the people that we’re trying to serve at the center.”

Mr. Pitasi, Dr. Rosengren-Hovee, Dr. Wood, Dr. Harris, and Dr. Smith have disclosed no relevant financial relationships.

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

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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

NEW ORLEANS – A monoclonal antibody targeting interferon-beta (IFN-beta) provided substantial reductions in the skin lesions associated with dermatomyositis in a double-blind, placebo-controlled phase 2 trial, according to results presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

“These findings support the inhibition of IFN-beta as a promising therapeutic strategy in skin-predominant disease,” said principal investigator Aaron Mangold, MD, associate professor of dermatology, Mayo Clinic, Scottsdale, Ariz.

Ted Bosworth/MDedge News

Dermatomyositis, a rare autoimmune inflammatory condition that typically involves both skeletal muscles and skin, is a challenging disease with a diverse set of potential complications.

Immunosuppressive and immunomodulatory agents are used with mixed success for myositis, but skin manifestations, which include papular eruptions, heliotrope rash, photoerythema, burning, and pruritus, are often the most troublesome and the most difficult to control. Treatment options other than immunomodulators that target cutaneous involvement – which include steroids, emollients, and photoprotection – are generally modestly effective, according to Dr. Mangold.
 

Targeting an elevated cytokine

Interest in IFN-beta, which is elevated in the blood of individuals with dermatomyositis, was triggered by evidence that this cytokine plays an important role in driving the skin inflammation, Dr. Mangold explained.

“The blood concentrations of IFN-beta are positively correlated with cutaneous disease activity and severity,” he said.

The study drug, currently known as PF-06823859 (Dazukibart), “is a potent, selective humanized IgG1-neutralizing antibody directed at IFN-beta,” Dr. Mangold said. A dose-ranging phase 1 study published 2 years ago provided evidence of acceptable pharmacokinetics and safety in healthy individuals to support treatment studies for disorders associated with elevated IFN-beta levels. In addition to dermatomyositis, this includes systemic lupus erythematosus.

In this phase 2 trial, patients whose condition was not improved by at least one standard-care therapy for skin manifestations of dermatomyositis were eligible if they had moderate to severe disease as measured with the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), according to Dr. Mangold. During the study, patients were allowed to remain on a disease modifying antirheumatic drug and/or prednisone if they had been on stable doses and did not change the dose.

Richard Usatine, MD

After a screening run-in, the trial had two blinded stages. In stage 1, 30 patients were randomly assigned either to 600 mg of PF-06823859 or to placebo, both administered intravenously every 4 weeks. A second cohort of 25 patients was randomly assigned in stage 2 to placebo, 150 mg of PF-06823859, or 600 mg of PF-06823859. The primary endpoint assessed at 12 weeks was a greater than 5-point reduction in CDASI score or greater than 40% CDASI improvement from baseline.

Both endpoints are associated with a clinically meaningful response in regard to an improved quality of life, Dr. Mangold noted.
 

Both doses better than placebo

In results from the stage 1 portion, the mean reduction in CDASI at 12 weeks after three doses of the assigned therapy was 18.8 points in the active-treatment group versus 3.9 points in the placebo group. In pooled data from stage 1 and 2, the reductions were 16.6 points, 19.2 points, and 2.9 points for the 150-mg, 600-mg, and placebo arms, respectively. Both doses achieved a highly significant advantage over placebo.

For both stages and doses, the response curves of the active-treatment groups and the placebo group diverged almost immediately. By 4 weeks, both measures of CDASI reductions on active therapy were significantly improved relative to placebo, and the response curves had a consistent downward slope through the end of the 12-week study, Dr. Mangold reported.

The majority of patients responded by either of the primary endpoint criteria. For a CDASI reduction of greater than 5 points, the response rates were 100% and 96% for the 150-mg and 600-mg doses of PF-06823859, respectively. The placebo response was 35.7%. For the CDASI reduction of greater than 40%, the rates were 80%, 82.1%, and 7.1% for the 150-mg, 600-mg, and placebo arms, respectively.

“There were no major safety concerns. Most of the treatment-emergent adverse events were mild, and adverse events did not have a relationship to dose,” Dr. Mangold said. Notably, there were no cases of herpes zoster, and infections of any kind were low in all study groups.

A phase 3 study is being planned with the 600-mg dose, according to Dr. Mangold, but he acknowledged that regulatory authorities have generally required endpoints for both cutaneous and muscle manifestations in previous trials of therapies for dermatomyositis.

It is not yet certain that “there will be a carve-out for skin,” he said in answer to a question about investigations moving forward. So far, studies have been focused on skin response. However, a meaningful degree of benefit against muscle involvement, which has not yet been well studied, has not been ruled out.

Even though this is a phase 2 trial with small numbers, it was controlled and blinded, and the potential of an inhibitor of IFN-beta to control the skin manifestations of dermatomyositis “is kind of a big deal,” said Paul Nghiem, MD, PhD, professor of dermatology, University of Washington, Seattle.

“There is definitely an unmet need for better therapies to control the skin involvement,” Dr. Nghiem said.

Hensin Tsao, MD, PhD, clinical director of the Melanoma and Pigmented Lesion Center at Massachusetts General Hospital, Boston, agreed. Like Dr. Nghiem, Dr. Tsao was a panelist during the late-breaker session where the study was presented, and he was impressed by the data.

“This is something that is definitely newsworthy,” Dr. Tsao said.

Dr. Mangold reports financial relationships with Actelion, Amgen, Corbus, Eli Lilly, Incyte, miRagen, Novartis, Regeneron, Solagenix, Sun Pharmaceuticals, Teva, and Pfizer, which provided funding for this trial. Both Dr. Nghiem and Dr. Tsao reported no relevant financial relationships.

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