MDedge Dermatology

To the Editor:

In a 2010 landmark paper, researchers reported that the Preexposure Prophylaxis Initiative (iPrEx) trial demonstrated that once-daily pre-exposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate, which was approved by the US Food and Drug Administration (FDA) and packaged together as Truvada (Gilead Sciences, Inc), achieved a 44% reduction in the incidence of HIV infection compared to the placebo arm of the study (64/1248 HIV infections in the placebo group vs 36/1251 in the intervention group).¹ Subsequently, the US Department of Health and Human Services proposed an initiative to reduce new HIV infections by 90% by 2030.² The Centers for Disease Control and Prevention estimates that 1.1 million Americans have an indication for PrEP, yet only approximately 400,000 individuals currently take PrEP.^3,4

Increasing awareness of PrEP and its indications is essential because PrEP exerts its greatest benefit when used broadly. Awareness among primary care and infectious disease physicians was reported at 76%⁵; awareness among other medical specialists remains unknown. Awareness of PrEP among dermatologists is important because dermatologists play an important role in the diagnosis and treatment of many sexually transmitted infections (STIs), which are a risk factor for transmission of HIV. As providers who treat STIs, dermatologists are in a prime position to educate patients about PrEP, refer them for treatment, and prescribe the regimen. We conducted a survey to assess dermatologists’ knowledge about and attitudes toward PrEP. We also provide a brief summary of prescribing information about common PrEP regimens to fill in the knowledge gap among dermatologists as a way to promote its utilization.

An electronic survey was distributed to 486 members of the Association of Professors of Dermatology based in the United States using the web-based survey application REDCap. The study was approved by the New York University Grossman School of Medicine (New York, New York) institutional review board. Eighty-one anonymous survey responses were completed and returned (response rate, 16.6%). Data were analyzed using descriptive statistics.

The mean age (SD) of respondents was 39.1 (9.7) years; 49.4% (40/81) were male; and 74.1% (60/81) were attending physicians, with a mean (SD) of 9.4 (8.6) years of practice. Clinical practices were predominantly from the northeast (46.9% [38/81]) and mostly in an academic setting (74.1% [60/81]). As shown in Table 1, most surveyed dermatologists reported being aware of PrEP (93.8% [76/81]), but a minority (42.0% [34/81]) were familiar with indications for its use; even fewer (4.9% [4/81]) were current prescribers. Referral to other physicians for PrEP was reported by 58.0% (47/81) of respondents.

Despite respondents’ awareness of PrEP as a preventive measure (93.8% [76/81]) and their willingness to prescribe it (67.9% [55/81]), many reported being largely unfamiliar with its indications (58.0% [47/81]) and uncomfortable discussing its adverse effects (72.8% [59/81]), conducting appropriate laboratory monitoring (84.0% [68/81]), and refilling existing prescriptions (77.8% [63/81]). Respondents’ lack of education about PrEP was a barrier to prescribing (51.9% [42/81] to 59.3% [48/81]) and explains why a small minority (4.9% [4/81]) currently prescribe the regimen.

Our study sought to characterize current clinical knowledge about and practice patterns of PrEP among dermatologists. Dermatologists often encounter patients who present with an STI, which is a risk factor for HIV infection, but our survey respondents reported several barriers to utilizing PrEP. The difference in the degree of respondents’ willingness to prescribe PrEP (67.9%) and those who self-identified as prescribers (4.9%) suggests a role for dermatologists in prescribing or discussing PrEP with their patients—albeit a currently undefined role.

The results of our study suggested that half (41/81) of dermatologists believe that PrEP prescription is out of their scope of practice, likely due to a combination of scheduling, laboratory monitoring, and medicolegal concerns. For dermatologists who are interested in being PrEP prescribers, our results suggested that closing the knowledge gap around PrEP among dermatologists through training and education could improve comfort with this medication and lead to changes in practice to prevent the spread of HIV infection.

PrEP is indicated for HIV-negative patients who have HIV-positive sexual partners, utilize barrier protection methods inconsistently, or had a diagnosis of an STI in the last 6 months.⁶ In 2012, the FDA approved once-daily use of emtricitabine plus tenofovir for primary prevention of HIV infection. Post hoc analysis of iPrEx trial data revealed that once-daily PrEP taken regularly had a 92% to 100% protective effect against HIV.⁷

Regrettably, real-world uptake of PrEP has been slower than desired. The most recent data (2021) show that nearly 1 million individuals worldwide take PrEP; however, this represents only approximately one-third of those eligible.⁸ Utilization is notably lower among Black and Latino populations who stand to gain the most from PrEP given their higher risk of contracting HIV compared to their White counterparts.⁹ As such, improving access to PrEP through expanded provider awareness is essential to decrease the risk for HIV infection and transmission.

Emtricitabine plus tenofovir is safe and well tolerated; more common adverse effects are headache, nausea, vomiting, rash, and loss of appetite. Tenofovir likely decreases bone mineral density, even in HIV-negative patients¹⁰; mineralization seems to recover after the medication is discontinued.¹¹ Rarely, tenofovir can increase the level of creatinine and hepatic transaminases; a recent report on its long-term side effects has shown small nonprogressive decreases in glomerular filtration rate.¹² Monitoring kidney function is a component of prescribing PrEP (Table 2).

In 2019, emtricitabine plus tenofovir was reformulated with tenofovir alafenamide; the new combination regimen received FDA approval for once-daily PrEP under the brand name Descovy (Gilead Sciences, Inc). The new formulation results in a lower blood concentration of tenofovir and has been reported to present less of a risk for bone and kidney toxicity.^13,14

Notably, emtricitabine plus tenofovir alafenamide might accumulate faster in peripheral lymphatic tissue than emtricitabine plus tenofovir disoproxil fumarate. This property has led to a new regimen known as “on-demand PrEP,” which follows a 2-1-1 dosing regimen: Patients take a double dose 2 to 24 hours before sexual activity, 1 dose on the day of sexual activity, and 1 dose the day after sexual activity.¹⁵ Because some patients at risk for HIV infection might not be consistently sexually active, on-demand PrEP allows them to cycle on and off the medication. Barriers to implementing on-demand PrEP include requiring that sexual activity be planned and an adverse effect profile similar to daily-use PrEP.¹⁶

The FDA recently approved a long-acting, once-monthly combination injectable PrEP of cabotegravir and rilpivirine.¹⁷ The long duration of action of this PrEP will benefit patients who report problems with medication adherence.

Our study demonstrates low frequency in prescribing patterns of PrEP among dermatologists and suggests that an addressable barrier to such prescribing is the lack of knowledge on how to prescribe it safely, which warrants further clinical investigation. We summarize an approach to prescribing PrEP in Table 2. Our study was limited by a small sample of mostly academic dermatologists and selection bias, which may diminish the generalizability of findings. A study of a larger, more representative group of dermatologists likely would show different prescribing patterns and degrees of knowledge about PrEP. Research is needed to study the impact of educational interventions that aim to increase both knowledge and prescribing of PrEP among dermatologists.

To the Editor:

In a 2010 landmark paper, researchers reported that the Preexposure Prophylaxis Initiative (iPrEx) trial demonstrated that once-daily pre-exposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate, which was approved by the US Food and Drug Administration (FDA) and packaged together as Truvada (Gilead Sciences, Inc), achieved a 44% reduction in the incidence of HIV infection compared to the placebo arm of the study (64/1248 HIV infections in the placebo group vs 36/1251 in the intervention group).¹ Subsequently, the US Department of Health and Human Services proposed an initiative to reduce new HIV infections by 90% by 2030.² The Centers for Disease Control and Prevention estimates that 1.1 million Americans have an indication for PrEP, yet only approximately 400,000 individuals currently take PrEP.^3,4

Increasing awareness of PrEP and its indications is essential because PrEP exerts its greatest benefit when used broadly. Awareness among primary care and infectious disease physicians was reported at 76%⁵; awareness among other medical specialists remains unknown. Awareness of PrEP among dermatologists is important because dermatologists play an important role in the diagnosis and treatment of many sexually transmitted infections (STIs), which are a risk factor for transmission of HIV. As providers who treat STIs, dermatologists are in a prime position to educate patients about PrEP, refer them for treatment, and prescribe the regimen. We conducted a survey to assess dermatologists’ knowledge about and attitudes toward PrEP. We also provide a brief summary of prescribing information about common PrEP regimens to fill in the knowledge gap among dermatologists as a way to promote its utilization.

An electronic survey was distributed to 486 members of the Association of Professors of Dermatology based in the United States using the web-based survey application REDCap. The study was approved by the New York University Grossman School of Medicine (New York, New York) institutional review board. Eighty-one anonymous survey responses were completed and returned (response rate, 16.6%). Data were analyzed using descriptive statistics.

The mean age (SD) of respondents was 39.1 (9.7) years; 49.4% (40/81) were male; and 74.1% (60/81) were attending physicians, with a mean (SD) of 9.4 (8.6) years of practice. Clinical practices were predominantly from the northeast (46.9% [38/81]) and mostly in an academic setting (74.1% [60/81]). As shown in Table 1, most surveyed dermatologists reported being aware of PrEP (93.8% [76/81]), but a minority (42.0% [34/81]) were familiar with indications for its use; even fewer (4.9% [4/81]) were current prescribers. Referral to other physicians for PrEP was reported by 58.0% (47/81) of respondents.

Despite respondents’ awareness of PrEP as a preventive measure (93.8% [76/81]) and their willingness to prescribe it (67.9% [55/81]), many reported being largely unfamiliar with its indications (58.0% [47/81]) and uncomfortable discussing its adverse effects (72.8% [59/81]), conducting appropriate laboratory monitoring (84.0% [68/81]), and refilling existing prescriptions (77.8% [63/81]). Respondents’ lack of education about PrEP was a barrier to prescribing (51.9% [42/81] to 59.3% [48/81]) and explains why a small minority (4.9% [4/81]) currently prescribe the regimen.

Our study sought to characterize current clinical knowledge about and practice patterns of PrEP among dermatologists. Dermatologists often encounter patients who present with an STI, which is a risk factor for HIV infection, but our survey respondents reported several barriers to utilizing PrEP. The difference in the degree of respondents’ willingness to prescribe PrEP (67.9%) and those who self-identified as prescribers (4.9%) suggests a role for dermatologists in prescribing or discussing PrEP with their patients—albeit a currently undefined role.

The results of our study suggested that half (41/81) of dermatologists believe that PrEP prescription is out of their scope of practice, likely due to a combination of scheduling, laboratory monitoring, and medicolegal concerns. For dermatologists who are interested in being PrEP prescribers, our results suggested that closing the knowledge gap around PrEP among dermatologists through training and education could improve comfort with this medication and lead to changes in practice to prevent the spread of HIV infection.

PrEP is indicated for HIV-negative patients who have HIV-positive sexual partners, utilize barrier protection methods inconsistently, or had a diagnosis of an STI in the last 6 months.⁶ In 2012, the FDA approved once-daily use of emtricitabine plus tenofovir for primary prevention of HIV infection. Post hoc analysis of iPrEx trial data revealed that once-daily PrEP taken regularly had a 92% to 100% protective effect against HIV.⁷

Regrettably, real-world uptake of PrEP has been slower than desired. The most recent data (2021) show that nearly 1 million individuals worldwide take PrEP; however, this represents only approximately one-third of those eligible.⁸ Utilization is notably lower among Black and Latino populations who stand to gain the most from PrEP given their higher risk of contracting HIV compared to their White counterparts.⁹ As such, improving access to PrEP through expanded provider awareness is essential to decrease the risk for HIV infection and transmission.

Emtricitabine plus tenofovir is safe and well tolerated; more common adverse effects are headache, nausea, vomiting, rash, and loss of appetite. Tenofovir likely decreases bone mineral density, even in HIV-negative patients¹⁰; mineralization seems to recover after the medication is discontinued.¹¹ Rarely, tenofovir can increase the level of creatinine and hepatic transaminases; a recent report on its long-term side effects has shown small nonprogressive decreases in glomerular filtration rate.¹² Monitoring kidney function is a component of prescribing PrEP (Table 2).

In 2019, emtricitabine plus tenofovir was reformulated with tenofovir alafenamide; the new combination regimen received FDA approval for once-daily PrEP under the brand name Descovy (Gilead Sciences, Inc). The new formulation results in a lower blood concentration of tenofovir and has been reported to present less of a risk for bone and kidney toxicity.^13,14

Notably, emtricitabine plus tenofovir alafenamide might accumulate faster in peripheral lymphatic tissue than emtricitabine plus tenofovir disoproxil fumarate. This property has led to a new regimen known as “on-demand PrEP,” which follows a 2-1-1 dosing regimen: Patients take a double dose 2 to 24 hours before sexual activity, 1 dose on the day of sexual activity, and 1 dose the day after sexual activity.¹⁵ Because some patients at risk for HIV infection might not be consistently sexually active, on-demand PrEP allows them to cycle on and off the medication. Barriers to implementing on-demand PrEP include requiring that sexual activity be planned and an adverse effect profile similar to daily-use PrEP.¹⁶

The FDA recently approved a long-acting, once-monthly combination injectable PrEP of cabotegravir and rilpivirine.¹⁷ The long duration of action of this PrEP will benefit patients who report problems with medication adherence.

Our study demonstrates low frequency in prescribing patterns of PrEP among dermatologists and suggests that an addressable barrier to such prescribing is the lack of knowledge on how to prescribe it safely, which warrants further clinical investigation. We summarize an approach to prescribing PrEP in Table 2. Our study was limited by a small sample of mostly academic dermatologists and selection bias, which may diminish the generalizability of findings. A study of a larger, more representative group of dermatologists likely would show different prescribing patterns and degrees of knowledge about PrEP. Research is needed to study the impact of educational interventions that aim to increase both knowledge and prescribing of PrEP among dermatologists.

To the Editor:

In a 2010 landmark paper, researchers reported that the Preexposure Prophylaxis Initiative (iPrEx) trial demonstrated that once-daily pre-exposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate, which was approved by the US Food and Drug Administration (FDA) and packaged together as Truvada (Gilead Sciences, Inc), achieved a 44% reduction in the incidence of HIV infection compared to the placebo arm of the study (64/1248 HIV infections in the placebo group vs 36/1251 in the intervention group).¹ Subsequently, the US Department of Health and Human Services proposed an initiative to reduce new HIV infections by 90% by 2030.² The Centers for Disease Control and Prevention estimates that 1.1 million Americans have an indication for PrEP, yet only approximately 400,000 individuals currently take PrEP.^3,4

Increasing awareness of PrEP and its indications is essential because PrEP exerts its greatest benefit when used broadly. Awareness among primary care and infectious disease physicians was reported at 76%⁵; awareness among other medical specialists remains unknown. Awareness of PrEP among dermatologists is important because dermatologists play an important role in the diagnosis and treatment of many sexually transmitted infections (STIs), which are a risk factor for transmission of HIV. As providers who treat STIs, dermatologists are in a prime position to educate patients about PrEP, refer them for treatment, and prescribe the regimen. We conducted a survey to assess dermatologists’ knowledge about and attitudes toward PrEP. We also provide a brief summary of prescribing information about common PrEP regimens to fill in the knowledge gap among dermatologists as a way to promote its utilization.

An electronic survey was distributed to 486 members of the Association of Professors of Dermatology based in the United States using the web-based survey application REDCap. The study was approved by the New York University Grossman School of Medicine (New York, New York) institutional review board. Eighty-one anonymous survey responses were completed and returned (response rate, 16.6%). Data were analyzed using descriptive statistics.

The mean age (SD) of respondents was 39.1 (9.7) years; 49.4% (40/81) were male; and 74.1% (60/81) were attending physicians, with a mean (SD) of 9.4 (8.6) years of practice. Clinical practices were predominantly from the northeast (46.9% [38/81]) and mostly in an academic setting (74.1% [60/81]). As shown in Table 1, most surveyed dermatologists reported being aware of PrEP (93.8% [76/81]), but a minority (42.0% [34/81]) were familiar with indications for its use; even fewer (4.9% [4/81]) were current prescribers. Referral to other physicians for PrEP was reported by 58.0% (47/81) of respondents.

Despite respondents’ awareness of PrEP as a preventive measure (93.8% [76/81]) and their willingness to prescribe it (67.9% [55/81]), many reported being largely unfamiliar with its indications (58.0% [47/81]) and uncomfortable discussing its adverse effects (72.8% [59/81]), conducting appropriate laboratory monitoring (84.0% [68/81]), and refilling existing prescriptions (77.8% [63/81]). Respondents’ lack of education about PrEP was a barrier to prescribing (51.9% [42/81] to 59.3% [48/81]) and explains why a small minority (4.9% [4/81]) currently prescribe the regimen.

Our study sought to characterize current clinical knowledge about and practice patterns of PrEP among dermatologists. Dermatologists often encounter patients who present with an STI, which is a risk factor for HIV infection, but our survey respondents reported several barriers to utilizing PrEP. The difference in the degree of respondents’ willingness to prescribe PrEP (67.9%) and those who self-identified as prescribers (4.9%) suggests a role for dermatologists in prescribing or discussing PrEP with their patients—albeit a currently undefined role.

The results of our study suggested that half (41/81) of dermatologists believe that PrEP prescription is out of their scope of practice, likely due to a combination of scheduling, laboratory monitoring, and medicolegal concerns. For dermatologists who are interested in being PrEP prescribers, our results suggested that closing the knowledge gap around PrEP among dermatologists through training and education could improve comfort with this medication and lead to changes in practice to prevent the spread of HIV infection.

PrEP is indicated for HIV-negative patients who have HIV-positive sexual partners, utilize barrier protection methods inconsistently, or had a diagnosis of an STI in the last 6 months.⁶ In 2012, the FDA approved once-daily use of emtricitabine plus tenofovir for primary prevention of HIV infection. Post hoc analysis of iPrEx trial data revealed that once-daily PrEP taken regularly had a 92% to 100% protective effect against HIV.⁷

Regrettably, real-world uptake of PrEP has been slower than desired. The most recent data (2021) show that nearly 1 million individuals worldwide take PrEP; however, this represents only approximately one-third of those eligible.⁸ Utilization is notably lower among Black and Latino populations who stand to gain the most from PrEP given their higher risk of contracting HIV compared to their White counterparts.⁹ As such, improving access to PrEP through expanded provider awareness is essential to decrease the risk for HIV infection and transmission.

Emtricitabine plus tenofovir is safe and well tolerated; more common adverse effects are headache, nausea, vomiting, rash, and loss of appetite. Tenofovir likely decreases bone mineral density, even in HIV-negative patients¹⁰; mineralization seems to recover after the medication is discontinued.¹¹ Rarely, tenofovir can increase the level of creatinine and hepatic transaminases; a recent report on its long-term side effects has shown small nonprogressive decreases in glomerular filtration rate.¹² Monitoring kidney function is a component of prescribing PrEP (Table 2).

In 2019, emtricitabine plus tenofovir was reformulated with tenofovir alafenamide; the new combination regimen received FDA approval for once-daily PrEP under the brand name Descovy (Gilead Sciences, Inc). The new formulation results in a lower blood concentration of tenofovir and has been reported to present less of a risk for bone and kidney toxicity.^13,14

Notably, emtricitabine plus tenofovir alafenamide might accumulate faster in peripheral lymphatic tissue than emtricitabine plus tenofovir disoproxil fumarate. This property has led to a new regimen known as “on-demand PrEP,” which follows a 2-1-1 dosing regimen: Patients take a double dose 2 to 24 hours before sexual activity, 1 dose on the day of sexual activity, and 1 dose the day after sexual activity.¹⁵ Because some patients at risk for HIV infection might not be consistently sexually active, on-demand PrEP allows them to cycle on and off the medication. Barriers to implementing on-demand PrEP include requiring that sexual activity be planned and an adverse effect profile similar to daily-use PrEP.¹⁶

The FDA recently approved a long-acting, once-monthly combination injectable PrEP of cabotegravir and rilpivirine.¹⁷ The long duration of action of this PrEP will benefit patients who report problems with medication adherence.

Our study demonstrates low frequency in prescribing patterns of PrEP among dermatologists and suggests that an addressable barrier to such prescribing is the lack of knowledge on how to prescribe it safely, which warrants further clinical investigation. We summarize an approach to prescribing PrEP in Table 2. Our study was limited by a small sample of mostly academic dermatologists and selection bias, which may diminish the generalizability of findings. A study of a larger, more representative group of dermatologists likely would show different prescribing patterns and degrees of knowledge about PrEP. Research is needed to study the impact of educational interventions that aim to increase both knowledge and prescribing of PrEP among dermatologists.

About 5% of traditional Medicare patients who had telehealth visits were seen virtually by out-of-state clinicians in the first half of 2021, according to a new study in JAMA Health Forum.

Since then, however, many states have restored restrictions that prevent physicians who are licensed in one state from having telehealth visits with patients unless they’re licensed in the state where the patients live.

RichLegg/Getty Images

This is not fair to many people who live in areas near state borders, the authors argued. For those patients, it is much more convenient to see their primary care physician in a virtual visit from home than to travel to the doctor’s office in another state. This convenience is enjoyed by most patients who reside elsewhere in their state because they’re seeing physicians who are licensed there.

Moreover, the paper said, patients who live in rural areas and in counties with relatively few physicians per capita would also benefit from relaxed telemedicine restrictions.

Using Medicare claims data, the researchers examined the characteristics of out-of-state (OOS) telemedicine visits for the 6 months from January to June 2021. They chose that period for two reasons: by then, health care had stabilized after the chaotic early phase of the pandemic, and in most states, the relaxation of licensing rules for OOS telehealth had not yet lapsed. Earlier periods of time were also used for certain types of comparisons.

Among fee-for-service Medicare beneficiaries, the number of OOS telemedicine visits peaked at 451,086 in April 2020 and slowly fell to 175,545 in June 2021, according to the study. The fraction of OOS telehealth visits among all virtual visits was 4.5% in April 2020 and increased to 5.6% by June 2021.
 

Staying close to home

Of all beneficiaries with a telemedicine visit in the study period, 33% lived within 15 miles of a state border. That cohort accounted for 57.2% of all OOS telemedicine visits.

The highest rates of OOS telehealth visits were seen in the District of Columbia (38.5%), Wyoming (25.6%), and North Dakota (21.1%). California (1%), Texas (2%), and Massachusetts (2.1%) had the lowest rates.

Though intuitive in retrospect, the correlation of OOS telemedicine use with proximity to state borders was one of the study’s most important findings, lead author Ateev Mehrotra, MD, a professor at Harvard Medical School, Boston, said in an interview. “It makes sense,” he said. “If you’re in D.C. and you need a cardiologist, you don’t think: ‘I’ll stay in D.C.’ No, Maryland is right there, so you might use a Maryland cardiologist. Now you’re out of state, even though that office might be only half a mile away from you.”

Similar dynamics, he noted, are seen in many metropolitan areas that border on other states, such as Cincinnati; Philadelphia; and Portland, Ore.

This finding lines up with another result of the study: The majority of patients who had OOS telemedicine visits had previously seen in person the doctor who conducted the virtual visit.

Across all OOS telemedicine visits in the first half of 2021, the researchers observed a prior in-person visit between March 2019 and the date of the virtual visit with the same patient and the same clinician in 62.8% of those visits. Across all in-state telehealth visits, 75.8% of them were made by patients who had seen the same clinician in person since March 2019. This preponderance of virtual visits to clinicians whom the patients had already seen in person reflects the fact that, during the pandemic, most physicians began conducting telehealth visits with their own patients, Dr. Mehrotra said.

It also lays to rest the concern that some states have had about allowing OOS telemedicine visits to physicians not licensed in those states, he added. “They think that all these docs from far away are going to start taking care of patients they don’t even know. But our study shows that isn’t the case. Most of the time, doctors are seeing a patient who’s switching over from in-person visits to out-of-state telemedicine.”
 

More specialty care sought

The dominant conditions that patients presented with were the same in OOS telemedicine and within-state virtual visits. However, the use of OOS telemedicine was higher for some types of specialized care.

For example, the rate of OOS telemedicine use, compared with all telemedicine use, was highest for cancer care (9.8%). Drilling down to more specific conditions, the top three in OOS telemedicine visits were assessment of organ transplant (13%); male reproductive cancers, such as prostate cancer (11.3%); and graft-related issues (10.2%).

The specialty trend was also evident in the types of OOS clinicians from whom Medicare patients sought virtual care. The rates of OOS telemedicine use as a percentage of all telemedicine use in particular specialties were highest for uncommon specialties, such as hematology/oncology, rheumatology, urology, medical oncology, and orthopedic surgery (8.5%). There was less use of OOS telemedicine as a percentage of all telemedicine among more common medical specialties (6.4%), mental health specialties (4.4%), and primary care (4.4%).

Despite its relatively low showing in this category, however, behavioral health was the leading condition treated in both within-state and OOS telemedicine visits, accounting for 30.7% and 25.8%, respectively, of those encounters.

States backslide on OOS telehealth

Since the end of the study period, over half of the states have restored some or all of the restrictions on OOS telemedicine that they had lifted during the pandemic.

According to Dr. Mehrotra, 22 states have some kind of regulation in place to allow an OOS clinician to conduct telehealth visits without being licensed in the state. This varies all the way from complete reciprocity with other states’ licenses to “emergency” telemedicine licenses. The other 28 states and Washington, D.C., require an OOS telemedicine practitioner to get a state license.

Various proposals have been floated to ameliorate this situation, the JAMA paper noted. These proposals include an expansion of the Interstate Medical Licensure Compact that the Federation of State Medical Boards organized in 2014. Since the pact became effective in 2014, at least 35 states and the District of Columbia have joined it. Those states have made it simpler for physicians to gain licensure in states other than their original state of licensure. However, Mehrotra said, it’s still not easy, and not many physicians have taken advantage of it.

One new wrinkle has emerged in this policy debate as a result of the Supreme Court decision overturning Roe v. Wade, he noted. Because people are using OOS telemedicine visits to get prescriptions to abort their fetuses, “that has changed the enthusiasm level for it among many states,” he said.

Dr. Mehrotra reported personal fees from the Pew Charitable Trust, Sanofi Pasteur, and Black Opal Ventures outside the submitted work. One coauthor reported receiving grants from Patient-Centered Outcomes Research, National Institute on Aging, Roundtrip, Independence Blue Cross; personal fees or salary from RAND Corporation from Verily Life Sciences; and that the American Telemedicine Association covered a conference fee. No other disclosures were reported.

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

About 5% of traditional Medicare patients who had telehealth visits were seen virtually by out-of-state clinicians in the first half of 2021, according to a new study in JAMA Health Forum.

Since then, however, many states have restored restrictions that prevent physicians who are licensed in one state from having telehealth visits with patients unless they’re licensed in the state where the patients live.

RichLegg/Getty Images

This is not fair to many people who live in areas near state borders, the authors argued. For those patients, it is much more convenient to see their primary care physician in a virtual visit from home than to travel to the doctor’s office in another state. This convenience is enjoyed by most patients who reside elsewhere in their state because they’re seeing physicians who are licensed there.

Moreover, the paper said, patients who live in rural areas and in counties with relatively few physicians per capita would also benefit from relaxed telemedicine restrictions.

Using Medicare claims data, the researchers examined the characteristics of out-of-state (OOS) telemedicine visits for the 6 months from January to June 2021. They chose that period for two reasons: by then, health care had stabilized after the chaotic early phase of the pandemic, and in most states, the relaxation of licensing rules for OOS telehealth had not yet lapsed. Earlier periods of time were also used for certain types of comparisons.

Among fee-for-service Medicare beneficiaries, the number of OOS telemedicine visits peaked at 451,086 in April 2020 and slowly fell to 175,545 in June 2021, according to the study. The fraction of OOS telehealth visits among all virtual visits was 4.5% in April 2020 and increased to 5.6% by June 2021.
 

Staying close to home

Of all beneficiaries with a telemedicine visit in the study period, 33% lived within 15 miles of a state border. That cohort accounted for 57.2% of all OOS telemedicine visits.

The highest rates of OOS telehealth visits were seen in the District of Columbia (38.5%), Wyoming (25.6%), and North Dakota (21.1%). California (1%), Texas (2%), and Massachusetts (2.1%) had the lowest rates.

Though intuitive in retrospect, the correlation of OOS telemedicine use with proximity to state borders was one of the study’s most important findings, lead author Ateev Mehrotra, MD, a professor at Harvard Medical School, Boston, said in an interview. “It makes sense,” he said. “If you’re in D.C. and you need a cardiologist, you don’t think: ‘I’ll stay in D.C.’ No, Maryland is right there, so you might use a Maryland cardiologist. Now you’re out of state, even though that office might be only half a mile away from you.”

Similar dynamics, he noted, are seen in many metropolitan areas that border on other states, such as Cincinnati; Philadelphia; and Portland, Ore.

This finding lines up with another result of the study: The majority of patients who had OOS telemedicine visits had previously seen in person the doctor who conducted the virtual visit.

Across all OOS telemedicine visits in the first half of 2021, the researchers observed a prior in-person visit between March 2019 and the date of the virtual visit with the same patient and the same clinician in 62.8% of those visits. Across all in-state telehealth visits, 75.8% of them were made by patients who had seen the same clinician in person since March 2019. This preponderance of virtual visits to clinicians whom the patients had already seen in person reflects the fact that, during the pandemic, most physicians began conducting telehealth visits with their own patients, Dr. Mehrotra said.

It also lays to rest the concern that some states have had about allowing OOS telemedicine visits to physicians not licensed in those states, he added. “They think that all these docs from far away are going to start taking care of patients they don’t even know. But our study shows that isn’t the case. Most of the time, doctors are seeing a patient who’s switching over from in-person visits to out-of-state telemedicine.”
 

More specialty care sought

The dominant conditions that patients presented with were the same in OOS telemedicine and within-state virtual visits. However, the use of OOS telemedicine was higher for some types of specialized care.

For example, the rate of OOS telemedicine use, compared with all telemedicine use, was highest for cancer care (9.8%). Drilling down to more specific conditions, the top three in OOS telemedicine visits were assessment of organ transplant (13%); male reproductive cancers, such as prostate cancer (11.3%); and graft-related issues (10.2%).

The specialty trend was also evident in the types of OOS clinicians from whom Medicare patients sought virtual care. The rates of OOS telemedicine use as a percentage of all telemedicine use in particular specialties were highest for uncommon specialties, such as hematology/oncology, rheumatology, urology, medical oncology, and orthopedic surgery (8.5%). There was less use of OOS telemedicine as a percentage of all telemedicine among more common medical specialties (6.4%), mental health specialties (4.4%), and primary care (4.4%).

Despite its relatively low showing in this category, however, behavioral health was the leading condition treated in both within-state and OOS telemedicine visits, accounting for 30.7% and 25.8%, respectively, of those encounters.

States backslide on OOS telehealth

Since the end of the study period, over half of the states have restored some or all of the restrictions on OOS telemedicine that they had lifted during the pandemic.

According to Dr. Mehrotra, 22 states have some kind of regulation in place to allow an OOS clinician to conduct telehealth visits without being licensed in the state. This varies all the way from complete reciprocity with other states’ licenses to “emergency” telemedicine licenses. The other 28 states and Washington, D.C., require an OOS telemedicine practitioner to get a state license.

Various proposals have been floated to ameliorate this situation, the JAMA paper noted. These proposals include an expansion of the Interstate Medical Licensure Compact that the Federation of State Medical Boards organized in 2014. Since the pact became effective in 2014, at least 35 states and the District of Columbia have joined it. Those states have made it simpler for physicians to gain licensure in states other than their original state of licensure. However, Mehrotra said, it’s still not easy, and not many physicians have taken advantage of it.

One new wrinkle has emerged in this policy debate as a result of the Supreme Court decision overturning Roe v. Wade, he noted. Because people are using OOS telemedicine visits to get prescriptions to abort their fetuses, “that has changed the enthusiasm level for it among many states,” he said.

Dr. Mehrotra reported personal fees from the Pew Charitable Trust, Sanofi Pasteur, and Black Opal Ventures outside the submitted work. One coauthor reported receiving grants from Patient-Centered Outcomes Research, National Institute on Aging, Roundtrip, Independence Blue Cross; personal fees or salary from RAND Corporation from Verily Life Sciences; and that the American Telemedicine Association covered a conference fee. No other disclosures were reported.

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

About 5% of traditional Medicare patients who had telehealth visits were seen virtually by out-of-state clinicians in the first half of 2021, according to a new study in JAMA Health Forum.

Since then, however, many states have restored restrictions that prevent physicians who are licensed in one state from having telehealth visits with patients unless they’re licensed in the state where the patients live.

RichLegg/Getty Images

This is not fair to many people who live in areas near state borders, the authors argued. For those patients, it is much more convenient to see their primary care physician in a virtual visit from home than to travel to the doctor’s office in another state. This convenience is enjoyed by most patients who reside elsewhere in their state because they’re seeing physicians who are licensed there.

Moreover, the paper said, patients who live in rural areas and in counties with relatively few physicians per capita would also benefit from relaxed telemedicine restrictions.

Using Medicare claims data, the researchers examined the characteristics of out-of-state (OOS) telemedicine visits for the 6 months from January to June 2021. They chose that period for two reasons: by then, health care had stabilized after the chaotic early phase of the pandemic, and in most states, the relaxation of licensing rules for OOS telehealth had not yet lapsed. Earlier periods of time were also used for certain types of comparisons.

Among fee-for-service Medicare beneficiaries, the number of OOS telemedicine visits peaked at 451,086 in April 2020 and slowly fell to 175,545 in June 2021, according to the study. The fraction of OOS telehealth visits among all virtual visits was 4.5% in April 2020 and increased to 5.6% by June 2021.
 

Staying close to home

Of all beneficiaries with a telemedicine visit in the study period, 33% lived within 15 miles of a state border. That cohort accounted for 57.2% of all OOS telemedicine visits.

The highest rates of OOS telehealth visits were seen in the District of Columbia (38.5%), Wyoming (25.6%), and North Dakota (21.1%). California (1%), Texas (2%), and Massachusetts (2.1%) had the lowest rates.

Though intuitive in retrospect, the correlation of OOS telemedicine use with proximity to state borders was one of the study’s most important findings, lead author Ateev Mehrotra, MD, a professor at Harvard Medical School, Boston, said in an interview. “It makes sense,” he said. “If you’re in D.C. and you need a cardiologist, you don’t think: ‘I’ll stay in D.C.’ No, Maryland is right there, so you might use a Maryland cardiologist. Now you’re out of state, even though that office might be only half a mile away from you.”

Similar dynamics, he noted, are seen in many metropolitan areas that border on other states, such as Cincinnati; Philadelphia; and Portland, Ore.

This finding lines up with another result of the study: The majority of patients who had OOS telemedicine visits had previously seen in person the doctor who conducted the virtual visit.

Across all OOS telemedicine visits in the first half of 2021, the researchers observed a prior in-person visit between March 2019 and the date of the virtual visit with the same patient and the same clinician in 62.8% of those visits. Across all in-state telehealth visits, 75.8% of them were made by patients who had seen the same clinician in person since March 2019. This preponderance of virtual visits to clinicians whom the patients had already seen in person reflects the fact that, during the pandemic, most physicians began conducting telehealth visits with their own patients, Dr. Mehrotra said.

It also lays to rest the concern that some states have had about allowing OOS telemedicine visits to physicians not licensed in those states, he added. “They think that all these docs from far away are going to start taking care of patients they don’t even know. But our study shows that isn’t the case. Most of the time, doctors are seeing a patient who’s switching over from in-person visits to out-of-state telemedicine.”
 

More specialty care sought

The dominant conditions that patients presented with were the same in OOS telemedicine and within-state virtual visits. However, the use of OOS telemedicine was higher for some types of specialized care.

For example, the rate of OOS telemedicine use, compared with all telemedicine use, was highest for cancer care (9.8%). Drilling down to more specific conditions, the top three in OOS telemedicine visits were assessment of organ transplant (13%); male reproductive cancers, such as prostate cancer (11.3%); and graft-related issues (10.2%).

The specialty trend was also evident in the types of OOS clinicians from whom Medicare patients sought virtual care. The rates of OOS telemedicine use as a percentage of all telemedicine use in particular specialties were highest for uncommon specialties, such as hematology/oncology, rheumatology, urology, medical oncology, and orthopedic surgery (8.5%). There was less use of OOS telemedicine as a percentage of all telemedicine among more common medical specialties (6.4%), mental health specialties (4.4%), and primary care (4.4%).

Despite its relatively low showing in this category, however, behavioral health was the leading condition treated in both within-state and OOS telemedicine visits, accounting for 30.7% and 25.8%, respectively, of those encounters.

States backslide on OOS telehealth

Since the end of the study period, over half of the states have restored some or all of the restrictions on OOS telemedicine that they had lifted during the pandemic.

According to Dr. Mehrotra, 22 states have some kind of regulation in place to allow an OOS clinician to conduct telehealth visits without being licensed in the state. This varies all the way from complete reciprocity with other states’ licenses to “emergency” telemedicine licenses. The other 28 states and Washington, D.C., require an OOS telemedicine practitioner to get a state license.

Various proposals have been floated to ameliorate this situation, the JAMA paper noted. These proposals include an expansion of the Interstate Medical Licensure Compact that the Federation of State Medical Boards organized in 2014. Since the pact became effective in 2014, at least 35 states and the District of Columbia have joined it. Those states have made it simpler for physicians to gain licensure in states other than their original state of licensure. However, Mehrotra said, it’s still not easy, and not many physicians have taken advantage of it.

One new wrinkle has emerged in this policy debate as a result of the Supreme Court decision overturning Roe v. Wade, he noted. Because people are using OOS telemedicine visits to get prescriptions to abort their fetuses, “that has changed the enthusiasm level for it among many states,” he said.

Dr. Mehrotra reported personal fees from the Pew Charitable Trust, Sanofi Pasteur, and Black Opal Ventures outside the submitted work. One coauthor reported receiving grants from Patient-Centered Outcomes Research, National Institute on Aging, Roundtrip, Independence Blue Cross; personal fees or salary from RAND Corporation from Verily Life Sciences; and that the American Telemedicine Association covered a conference fee. No other disclosures were reported.

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

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare life-threatening condition that most often is seen in patients with end-stage renal disease at a rate of 35 per 10,000 chronic dialysis patients.¹ It less commonly has been described in nonuremic patients. The exact incidence of nonuremic calciphylaxis is unknown, but multiple risk factors have been identified, such as alcoholic liver disease, primary hyperparathyroidism, connective tissue diseases, and underlying malignancies. Other less common risk factors include type 2 diabetes mellitus, hypercoagulable disorders, obesity, hypoalbuminemia, and warfarin/ corticosteroid use.² However, most often no obvious triggers are identified.¹

Regardless of the etiology, calciphylaxis is characterized by the calcification of blood vessels and connective tissues, leading to vessel injury, intimal fibrosis, and thrombosis, followed by ischemic necrosis of the skin and soft tissue. It is postulated that microvascular calcification occurs as an active cell-mediated process that depends on the balance between the promoters and inhibitors of calcification.¹ In our patient, liver disease likely predisposed formation of calcification through the creation of an environment susceptible to vascular injury via decreased synthesis of proteins C and S.³ Synthesis of fetuin-A, a protein that acts as a circulating inhibitor of vascular ossification/calcification, also is decreased in calcification. Another inhibitor of calcification, matrix Gla protein, is unable to undergo activation through vitamin K–dependent carboxylation secondary to liver disease–induced vitamin K deficiency.³ Microvascular calcification without calciphylaxis may occur in other conditions such as type 2 diabetes mellitus. Therefore, clinicopathologic correlation is important in determining the diagnosis.

Calciphylaxis has a variety of clinical presentations depending on the stage of disease. It begins as a fixed, indurated, livedo reticularis–like plaque. The lesions become increasingly violaceous with intermixed areas of light blanched skin secondary to ischemia and then develop retiform pupura.⁴ Eventually, affected sites can become bullous and ulcerate or form a necrotic eschar. Severe pain is a cardinal feature throughout all stages.⁴ Lesions in nonuremic calciphylaxis most commonly are located in the central and/or proximal areas of the body.²

Clinical suspicion is essential for diagnosis. Skin biopsy is the standard method for confirmation in unclear cases. The classic histologic features include intravascular and extravascular calcification, microthrombosis, and fibrointimal hyperplasia of the small dermal and subcutaneous arteries and arterioles, leading to ischemia and intense septal panniculitis.¹ Von Kossa immunostaining is used to increase the detection of calcium deposits (Figure 1).¹ In addition to the classic changes, our case demonstrated a rare histologic variant with pseudoxanthoma elasticum (PXE)–like changes (Figure 2), which are thought to occur secondary to pathologic elastin fibrogenesis or increased proteolytic activity resulting in abnormal remodeling of the extracellular matrix in the setting of increased calcification of elastin fibers.⁵ Detection of PXE-like changes may be a helpful clue when specimens lack other characteristic signs.

Wound care, pain control, and addressing underlying causes are mainstays of therapy. Sodium thiosulfate, an antioxidant with vasodilatory properties that also inhibits adipocyte calcification and blocks the ability of adipocytes to induce calcification of vascular smooth-muscle cells, also is useful. Antibiotic prophylaxis is not indicated.¹

Even with treatment, both uremic and nonuremic calciphylaxis have a dismal prognosis; 1-year mortality is approximately 50% to 60% and rises to 80% at 2 years.⁴ Lesion location affects prognosis, and more proximal lesions portend worse outcomes. In patients with both proximal and distal lesions, there is a 90% mortality rate within 1 year. Ulceration also portends worse outcomes, as the wounds often are resistant to healing and act as nidi for infection.⁴ Septicemia is the most common cause of death.¹

Ecthyma gangrenosum is a cutaneous manifestation secondary to an infection most commonly associated with Pseudomonas aeruginosa.⁶ It often presents in immunocompromised patients with an underlying gramnegative septicemia.⁷ The clinical presentation initially begins with painless macules that rapidly progress into necrotic ulcers, usually accompanied by associated systemic symptoms such as fever, chills, and hypotension. Histopathology reveals numerous gram-negative rods around necrotic vessels.⁷

Idiopathic purpura fulminans is the rarest form of purpura fulminans. It is caused by autoantibody formation against protein S, resulting in protein S depletion and subsequent hypercoagulability.⁸ It usually occurs 7 to 10 days after the onset of a precipitating infection. Lesions begin as erythematous macules that progress within hours to painful, sharply defined areas of purpura and hemorrhagic cutaneous necrosis that may extend to deeper tissues.⁸ Secondary infection of gangrenous tissue may occur. Distribution usually is diffuse and signs of septic shock and disseminated intravascular coagulation usually are present.

Hughes syndrome, also known as antiphospholipid syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent arterial or venous thrombosis.⁹ Cutaneous manifestations consist of livedo reticularis, arterial and venous ulcers, and superficial thrombophlebitis.¹⁰ Laboratory testing for antiphospholipid antibodies and obtaining a detailed history of the patient’s cardiovascular health are crucial for diagnosis.⁹

Necrotizing fasciitis typically begins as an inconspicuous superficial cutaneous infection that rapidly is transmitted to the fascia. Infection can spread along fascial planes for several days without affecting the overlying skin, leading to delayed diagnosis.¹¹ The first signs to appear are disproportionate pain and a change in skin color to reddish-purple or bluish-gray. Next, the skin will become indurated, swollen, shiny, and more painful.¹¹ Skin breakdown will begin in 3 to 5 days and is accompanied by bullae and cutaneous gangrene. The involved area becomes painless due to thrombosis of the small vessels that supply the superficial nerves.¹² Septic shock ultimately will develop if untreated.

We present a rare case of nonuremic calciphylaxis. We encourage dermatologists to include calciphylaxis in the differential when evaluating any patient with a painful retiform rash or ulcerated eschar, even in the absence of renal disease.

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare life-threatening condition that most often is seen in patients with end-stage renal disease at a rate of 35 per 10,000 chronic dialysis patients.¹ It less commonly has been described in nonuremic patients. The exact incidence of nonuremic calciphylaxis is unknown, but multiple risk factors have been identified, such as alcoholic liver disease, primary hyperparathyroidism, connective tissue diseases, and underlying malignancies. Other less common risk factors include type 2 diabetes mellitus, hypercoagulable disorders, obesity, hypoalbuminemia, and warfarin/ corticosteroid use.² However, most often no obvious triggers are identified.¹

Regardless of the etiology, calciphylaxis is characterized by the calcification of blood vessels and connective tissues, leading to vessel injury, intimal fibrosis, and thrombosis, followed by ischemic necrosis of the skin and soft tissue. It is postulated that microvascular calcification occurs as an active cell-mediated process that depends on the balance between the promoters and inhibitors of calcification.¹ In our patient, liver disease likely predisposed formation of calcification through the creation of an environment susceptible to vascular injury via decreased synthesis of proteins C and S.³ Synthesis of fetuin-A, a protein that acts as a circulating inhibitor of vascular ossification/calcification, also is decreased in calcification. Another inhibitor of calcification, matrix Gla protein, is unable to undergo activation through vitamin K–dependent carboxylation secondary to liver disease–induced vitamin K deficiency.³ Microvascular calcification without calciphylaxis may occur in other conditions such as type 2 diabetes mellitus. Therefore, clinicopathologic correlation is important in determining the diagnosis.

Calciphylaxis has a variety of clinical presentations depending on the stage of disease. It begins as a fixed, indurated, livedo reticularis–like plaque. The lesions become increasingly violaceous with intermixed areas of light blanched skin secondary to ischemia and then develop retiform pupura.⁴ Eventually, affected sites can become bullous and ulcerate or form a necrotic eschar. Severe pain is a cardinal feature throughout all stages.⁴ Lesions in nonuremic calciphylaxis most commonly are located in the central and/or proximal areas of the body.²

Clinical suspicion is essential for diagnosis. Skin biopsy is the standard method for confirmation in unclear cases. The classic histologic features include intravascular and extravascular calcification, microthrombosis, and fibrointimal hyperplasia of the small dermal and subcutaneous arteries and arterioles, leading to ischemia and intense septal panniculitis.¹ Von Kossa immunostaining is used to increase the detection of calcium deposits (Figure 1).¹ In addition to the classic changes, our case demonstrated a rare histologic variant with pseudoxanthoma elasticum (PXE)–like changes (Figure 2), which are thought to occur secondary to pathologic elastin fibrogenesis or increased proteolytic activity resulting in abnormal remodeling of the extracellular matrix in the setting of increased calcification of elastin fibers.⁵ Detection of PXE-like changes may be a helpful clue when specimens lack other characteristic signs.

Wound care, pain control, and addressing underlying causes are mainstays of therapy. Sodium thiosulfate, an antioxidant with vasodilatory properties that also inhibits adipocyte calcification and blocks the ability of adipocytes to induce calcification of vascular smooth-muscle cells, also is useful. Antibiotic prophylaxis is not indicated.¹

Even with treatment, both uremic and nonuremic calciphylaxis have a dismal prognosis; 1-year mortality is approximately 50% to 60% and rises to 80% at 2 years.⁴ Lesion location affects prognosis, and more proximal lesions portend worse outcomes. In patients with both proximal and distal lesions, there is a 90% mortality rate within 1 year. Ulceration also portends worse outcomes, as the wounds often are resistant to healing and act as nidi for infection.⁴ Septicemia is the most common cause of death.¹

Ecthyma gangrenosum is a cutaneous manifestation secondary to an infection most commonly associated with Pseudomonas aeruginosa.⁶ It often presents in immunocompromised patients with an underlying gramnegative septicemia.⁷ The clinical presentation initially begins with painless macules that rapidly progress into necrotic ulcers, usually accompanied by associated systemic symptoms such as fever, chills, and hypotension. Histopathology reveals numerous gram-negative rods around necrotic vessels.⁷

Idiopathic purpura fulminans is the rarest form of purpura fulminans. It is caused by autoantibody formation against protein S, resulting in protein S depletion and subsequent hypercoagulability.⁸ It usually occurs 7 to 10 days after the onset of a precipitating infection. Lesions begin as erythematous macules that progress within hours to painful, sharply defined areas of purpura and hemorrhagic cutaneous necrosis that may extend to deeper tissues.⁸ Secondary infection of gangrenous tissue may occur. Distribution usually is diffuse and signs of septic shock and disseminated intravascular coagulation usually are present.

Hughes syndrome, also known as antiphospholipid syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent arterial or venous thrombosis.⁹ Cutaneous manifestations consist of livedo reticularis, arterial and venous ulcers, and superficial thrombophlebitis.¹⁰ Laboratory testing for antiphospholipid antibodies and obtaining a detailed history of the patient’s cardiovascular health are crucial for diagnosis.⁹

Necrotizing fasciitis typically begins as an inconspicuous superficial cutaneous infection that rapidly is transmitted to the fascia. Infection can spread along fascial planes for several days without affecting the overlying skin, leading to delayed diagnosis.¹¹ The first signs to appear are disproportionate pain and a change in skin color to reddish-purple or bluish-gray. Next, the skin will become indurated, swollen, shiny, and more painful.¹¹ Skin breakdown will begin in 3 to 5 days and is accompanied by bullae and cutaneous gangrene. The involved area becomes painless due to thrombosis of the small vessels that supply the superficial nerves.¹² Septic shock ultimately will develop if untreated.

We present a rare case of nonuremic calciphylaxis. We encourage dermatologists to include calciphylaxis in the differential when evaluating any patient with a painful retiform rash or ulcerated eschar, even in the absence of renal disease.

The Diagnosis: Calciphylaxis

Calciphylaxis is a rare life-threatening condition that most often is seen in patients with end-stage renal disease at a rate of 35 per 10,000 chronic dialysis patients.¹ It less commonly has been described in nonuremic patients. The exact incidence of nonuremic calciphylaxis is unknown, but multiple risk factors have been identified, such as alcoholic liver disease, primary hyperparathyroidism, connective tissue diseases, and underlying malignancies. Other less common risk factors include type 2 diabetes mellitus, hypercoagulable disorders, obesity, hypoalbuminemia, and warfarin/ corticosteroid use.² However, most often no obvious triggers are identified.¹

Regardless of the etiology, calciphylaxis is characterized by the calcification of blood vessels and connective tissues, leading to vessel injury, intimal fibrosis, and thrombosis, followed by ischemic necrosis of the skin and soft tissue. It is postulated that microvascular calcification occurs as an active cell-mediated process that depends on the balance between the promoters and inhibitors of calcification.¹ In our patient, liver disease likely predisposed formation of calcification through the creation of an environment susceptible to vascular injury via decreased synthesis of proteins C and S.³ Synthesis of fetuin-A, a protein that acts as a circulating inhibitor of vascular ossification/calcification, also is decreased in calcification. Another inhibitor of calcification, matrix Gla protein, is unable to undergo activation through vitamin K–dependent carboxylation secondary to liver disease–induced vitamin K deficiency.³ Microvascular calcification without calciphylaxis may occur in other conditions such as type 2 diabetes mellitus. Therefore, clinicopathologic correlation is important in determining the diagnosis.

Calciphylaxis has a variety of clinical presentations depending on the stage of disease. It begins as a fixed, indurated, livedo reticularis–like plaque. The lesions become increasingly violaceous with intermixed areas of light blanched skin secondary to ischemia and then develop retiform pupura.⁴ Eventually, affected sites can become bullous and ulcerate or form a necrotic eschar. Severe pain is a cardinal feature throughout all stages.⁴ Lesions in nonuremic calciphylaxis most commonly are located in the central and/or proximal areas of the body.²

Clinical suspicion is essential for diagnosis. Skin biopsy is the standard method for confirmation in unclear cases. The classic histologic features include intravascular and extravascular calcification, microthrombosis, and fibrointimal hyperplasia of the small dermal and subcutaneous arteries and arterioles, leading to ischemia and intense septal panniculitis.¹ Von Kossa immunostaining is used to increase the detection of calcium deposits (Figure 1).¹ In addition to the classic changes, our case demonstrated a rare histologic variant with pseudoxanthoma elasticum (PXE)–like changes (Figure 2), which are thought to occur secondary to pathologic elastin fibrogenesis or increased proteolytic activity resulting in abnormal remodeling of the extracellular matrix in the setting of increased calcification of elastin fibers.⁵ Detection of PXE-like changes may be a helpful clue when specimens lack other characteristic signs.

Wound care, pain control, and addressing underlying causes are mainstays of therapy. Sodium thiosulfate, an antioxidant with vasodilatory properties that also inhibits adipocyte calcification and blocks the ability of adipocytes to induce calcification of vascular smooth-muscle cells, also is useful. Antibiotic prophylaxis is not indicated.¹

Even with treatment, both uremic and nonuremic calciphylaxis have a dismal prognosis; 1-year mortality is approximately 50% to 60% and rises to 80% at 2 years.⁴ Lesion location affects prognosis, and more proximal lesions portend worse outcomes. In patients with both proximal and distal lesions, there is a 90% mortality rate within 1 year. Ulceration also portends worse outcomes, as the wounds often are resistant to healing and act as nidi for infection.⁴ Septicemia is the most common cause of death.¹

Ecthyma gangrenosum is a cutaneous manifestation secondary to an infection most commonly associated with Pseudomonas aeruginosa.⁶ It often presents in immunocompromised patients with an underlying gramnegative septicemia.⁷ The clinical presentation initially begins with painless macules that rapidly progress into necrotic ulcers, usually accompanied by associated systemic symptoms such as fever, chills, and hypotension. Histopathology reveals numerous gram-negative rods around necrotic vessels.⁷

Idiopathic purpura fulminans is the rarest form of purpura fulminans. It is caused by autoantibody formation against protein S, resulting in protein S depletion and subsequent hypercoagulability.⁸ It usually occurs 7 to 10 days after the onset of a precipitating infection. Lesions begin as erythematous macules that progress within hours to painful, sharply defined areas of purpura and hemorrhagic cutaneous necrosis that may extend to deeper tissues.⁸ Secondary infection of gangrenous tissue may occur. Distribution usually is diffuse and signs of septic shock and disseminated intravascular coagulation usually are present.

Hughes syndrome, also known as antiphospholipid syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent arterial or venous thrombosis.⁹ Cutaneous manifestations consist of livedo reticularis, arterial and venous ulcers, and superficial thrombophlebitis.¹⁰ Laboratory testing for antiphospholipid antibodies and obtaining a detailed history of the patient’s cardiovascular health are crucial for diagnosis.⁹

Necrotizing fasciitis typically begins as an inconspicuous superficial cutaneous infection that rapidly is transmitted to the fascia. Infection can spread along fascial planes for several days without affecting the overlying skin, leading to delayed diagnosis.¹¹ The first signs to appear are disproportionate pain and a change in skin color to reddish-purple or bluish-gray. Next, the skin will become indurated, swollen, shiny, and more painful.¹¹ Skin breakdown will begin in 3 to 5 days and is accompanied by bullae and cutaneous gangrene. The involved area becomes painless due to thrombosis of the small vessels that supply the superficial nerves.¹² Septic shock ultimately will develop if untreated.

We present a rare case of nonuremic calciphylaxis. We encourage dermatologists to include calciphylaxis in the differential when evaluating any patient with a painful retiform rash or ulcerated eschar, even in the absence of renal disease.

When counseling patients with acne about a treatment plan, consider the mnemonic “CLEAR,” advises Julie C. Harper, MD, who came up with this aid to use when treating this group of patients.

During a presentation at Medscape Live’s annual Coastal Dermatology Symposium, Dr. Harper, who practices at Dermatology and Skin Care of Birmingham, Ala., elaborated on the mnemonic, as follows:

C: Communicate expectations. “I look right at the acne patient and say, ‘I know you don’t just want to be better; I know you want to be clear,’ ” she said at the meeting. “ ‘That’s my goal for you, too. That may take us more than one visit and more than one treatment, but I am on your team, and that’s what we’re shooting for.’ If you don’t communicate that, they’re going to think that their acne is not that important to you.”

L: Listen for clues to customize the patient’s treatment. “We’re quick to say, ‘my patients don’t do what I recommend,’ or ‘they didn’t do what the last doctor recommended,’ ” Dr. Harper said. “Sometimes that is true, but there may be a reason why. Maybe the medication was too expensive. Maybe it was bleaching their fabrics. Maybe the regimen was too complex. Listen for opportunities to make adjustments to get their acne closer to clear.”

E: Treat early to improve quality of life and to decrease the risk of scarring. “I have a laser in my practice that is good at treating acne scarring,” she said. “Do I ever look at my patient and say, ‘don’t worry about those scars; I can make them go away?’ No. I look at them and say, ‘we can maybe make this 40% better,’ something like that. We have to prevent acne scars, because we’re not good at treating them.”

A: Treat aggressively with more combination therapies, more hormonal therapies, more isotretinoin, and perhaps more prior authorizations. She characterized the effort to obtain a prior authorization as “our megaphone back to insurance companies that says, ‘we think it is worth taking the time to do this prior authorization because the acne patient will benefit.’ ”

R: Don’t resist isotretinoin. Dr. Harper, who began practicing dermatology more than 20 years ago, said that over time, she has gradually prescribed more isotretinoin for her patients with acne. “It’s not a first-line [treatment], but I’m not afraid of it. If I can’t get somebody clear on other oral or topical treatments, we are going to try isotretinoin.”

The goal of acne treatment, she added, is to affect four key aspects of pathogenesis: follicular epithelial hyperproliferation, inflammation, Cutibacterium acnes (C. acnes), and sebum. “That’s what we’re always shooting for,” she said.

Dr. Harper is a past president of the American Acne & Rosacea Society. She disclosed that she serves as an advisor or consultant for Almirall, BioPharmX, Cassiopeia, Cutanea, Cutera, Dermira, EPI, Galderma, LaRoche-Posay, Ortho, Vyne, Sol Gel, and Sun. She also serves as a speaker or member of a speaker’s bureau for Almirall, EPI, Galderma, Ortho, and Vyne.

Medscape Live and this news organization are owned by the same parent company.

When counseling patients with acne about a treatment plan, consider the mnemonic “CLEAR,” advises Julie C. Harper, MD, who came up with this aid to use when treating this group of patients.

During a presentation at Medscape Live’s annual Coastal Dermatology Symposium, Dr. Harper, who practices at Dermatology and Skin Care of Birmingham, Ala., elaborated on the mnemonic, as follows:

C: Communicate expectations. “I look right at the acne patient and say, ‘I know you don’t just want to be better; I know you want to be clear,’ ” she said at the meeting. “ ‘That’s my goal for you, too. That may take us more than one visit and more than one treatment, but I am on your team, and that’s what we’re shooting for.’ If you don’t communicate that, they’re going to think that their acne is not that important to you.”

L: Listen for clues to customize the patient’s treatment. “We’re quick to say, ‘my patients don’t do what I recommend,’ or ‘they didn’t do what the last doctor recommended,’ ” Dr. Harper said. “Sometimes that is true, but there may be a reason why. Maybe the medication was too expensive. Maybe it was bleaching their fabrics. Maybe the regimen was too complex. Listen for opportunities to make adjustments to get their acne closer to clear.”

E: Treat early to improve quality of life and to decrease the risk of scarring. “I have a laser in my practice that is good at treating acne scarring,” she said. “Do I ever look at my patient and say, ‘don’t worry about those scars; I can make them go away?’ No. I look at them and say, ‘we can maybe make this 40% better,’ something like that. We have to prevent acne scars, because we’re not good at treating them.”

A: Treat aggressively with more combination therapies, more hormonal therapies, more isotretinoin, and perhaps more prior authorizations. She characterized the effort to obtain a prior authorization as “our megaphone back to insurance companies that says, ‘we think it is worth taking the time to do this prior authorization because the acne patient will benefit.’ ”

R: Don’t resist isotretinoin. Dr. Harper, who began practicing dermatology more than 20 years ago, said that over time, she has gradually prescribed more isotretinoin for her patients with acne. “It’s not a first-line [treatment], but I’m not afraid of it. If I can’t get somebody clear on other oral or topical treatments, we are going to try isotretinoin.”

The goal of acne treatment, she added, is to affect four key aspects of pathogenesis: follicular epithelial hyperproliferation, inflammation, Cutibacterium acnes (C. acnes), and sebum. “That’s what we’re always shooting for,” she said.

Dr. Harper is a past president of the American Acne & Rosacea Society. She disclosed that she serves as an advisor or consultant for Almirall, BioPharmX, Cassiopeia, Cutanea, Cutera, Dermira, EPI, Galderma, LaRoche-Posay, Ortho, Vyne, Sol Gel, and Sun. She also serves as a speaker or member of a speaker’s bureau for Almirall, EPI, Galderma, Ortho, and Vyne.

Medscape Live and this news organization are owned by the same parent company.

When counseling patients with acne about a treatment plan, consider the mnemonic “CLEAR,” advises Julie C. Harper, MD, who came up with this aid to use when treating this group of patients.

During a presentation at Medscape Live’s annual Coastal Dermatology Symposium, Dr. Harper, who practices at Dermatology and Skin Care of Birmingham, Ala., elaborated on the mnemonic, as follows:

C: Communicate expectations. “I look right at the acne patient and say, ‘I know you don’t just want to be better; I know you want to be clear,’ ” she said at the meeting. “ ‘That’s my goal for you, too. That may take us more than one visit and more than one treatment, but I am on your team, and that’s what we’re shooting for.’ If you don’t communicate that, they’re going to think that their acne is not that important to you.”

L: Listen for clues to customize the patient’s treatment. “We’re quick to say, ‘my patients don’t do what I recommend,’ or ‘they didn’t do what the last doctor recommended,’ ” Dr. Harper said. “Sometimes that is true, but there may be a reason why. Maybe the medication was too expensive. Maybe it was bleaching their fabrics. Maybe the regimen was too complex. Listen for opportunities to make adjustments to get their acne closer to clear.”

E: Treat early to improve quality of life and to decrease the risk of scarring. “I have a laser in my practice that is good at treating acne scarring,” she said. “Do I ever look at my patient and say, ‘don’t worry about those scars; I can make them go away?’ No. I look at them and say, ‘we can maybe make this 40% better,’ something like that. We have to prevent acne scars, because we’re not good at treating them.”

A: Treat aggressively with more combination therapies, more hormonal therapies, more isotretinoin, and perhaps more prior authorizations. She characterized the effort to obtain a prior authorization as “our megaphone back to insurance companies that says, ‘we think it is worth taking the time to do this prior authorization because the acne patient will benefit.’ ”

R: Don’t resist isotretinoin. Dr. Harper, who began practicing dermatology more than 20 years ago, said that over time, she has gradually prescribed more isotretinoin for her patients with acne. “It’s not a first-line [treatment], but I’m not afraid of it. If I can’t get somebody clear on other oral or topical treatments, we are going to try isotretinoin.”

The goal of acne treatment, she added, is to affect four key aspects of pathogenesis: follicular epithelial hyperproliferation, inflammation, Cutibacterium acnes (C. acnes), and sebum. “That’s what we’re always shooting for,” she said.

Dr. Harper is a past president of the American Acne & Rosacea Society. She disclosed that she serves as an advisor or consultant for Almirall, BioPharmX, Cassiopeia, Cutanea, Cutera, Dermira, EPI, Galderma, LaRoche-Posay, Ortho, Vyne, Sol Gel, and Sun. She also serves as a speaker or member of a speaker’s bureau for Almirall, EPI, Galderma, Ortho, and Vyne.

Medscape Live and this news organization are owned by the same parent company.

All atopic diseases, as well as environmental and parental factors, appear to be linked with hand eczema (HE), a longitudinal study from Finland has shown.

“In this population-based study, all atopic diseases, not only atopic dermatitis, were found as individual risk factors for HE. In addition, female gender, obesity and mold exposure increased the risk of HE,” wrote Marjut Koskelo, MD, and her colleagues at the University of Oulu in Finland. Their report was published in Contact Dermatitis.

“Parental allergy was also a risk factor of offspring’s HE. Moderate or high physical activity as well as owning a dog appeared as protective factors of HE. No association was found between other lifestyle factors and HE,” they added.

Hand eczema is one of the most common skin disorders and is the most common occupational skin disease, the authors wrote. Many risk factors, including atopic dermatitis, are known to be linked with HE, but whether various other factors might also be linked has not been well studied.

The research team investigated the link between HE and atopic diseases, parental factors, environmental factors (exposure to mold, keeping animals), and lifestyle factors (physical activity, obesity, tobacco and alcohol use).

They analyzed data of people who took part in the Northern Finland Birth Cohort 1966 Study. The data, collected since 1965, includes details about 12,055 mothers in northern Finland who were expected to deliver babies in 1966, and their 12,058 live-born children. The children have been followed over the years with questionnaires and clinical examinations, and their parents have been followed by national registers and medical reports.

For the 46-year follow-up, 6,830 respondents aged 45-46 years, roughly half of them women, completed a 132-question form covering physical health, lifestyle, environmental factors, socioeconomic status, and history of hand eczema and other atopic diseases.

In the statistical analysis, the researchers adjusted for atopic dermatitis, asthma, allergic rhinoconjunctivitis, education level, body mass index, maternal BMI, parental allergy, physical activity, living on a farm, and mold exposure and symptoms.

Of the 900 respondents who reported having had HE, 592 (65.8%) were women and 308 (34.2%) were men (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.49-2.0).
 

Various factors linked with hand eczema risk

The authors found the following:

• Atopic diseases and HE were linked: atopic dermatitis (adjusted odds ratio [aOR], 9.66; 95% CI, 8.03-11.66), asthma (aOR, 1.38; 95% CI, 1.12-1.71), and allergic rhinoconjunctivitis (aOR, 1.28; 95% CI, 1.04-1.56). Sex did not affect the link between atopic diseases and HE.
• Respondents who reported visible mold or mold odor in their apartments had higher risk for HE than did those without a history of mold exposure (OR, 1.32; 95% CI, 1.07-1.61).
• Obesity was linked with HE (OR, 3.44; 95% CI, 1.05-22.8), but smoking status, alcohol intake, and education level were not statistically significant risk factors for HE.
• Participants who reported moderate or high physical activity had lower risk for HE (OR, 0.78; 95% CI, 0.64-0.94; and OR, 0.56; 95% CI, 0.33-0.91, respectively) than those who were less active.
• Parental allergy increased risk for HE (OR, 1.98; 95% CI, 1.70-2.30); as maternal age, BMI, and menarche age increased, so did the risk for the child’s HE, but the increases were not statistically significant; and no significant links were found between maternal tobacco smoking, parental asthma, birth weight, parity, gestational age, and HE.
• Dog owners had less risk for HE than did people without a dog (OR, 0.83; 95% CI, 0.71-0.97); links between cat or farm animal owners and HE were not significant.

“There is a strong association between hand eczema and atopic diseases,” Maya Jonas, MD, clinical assistant professor of dermatology at The Ohio State University Wexner Medical Center in Columbus, told this news organization.

“When evaluating patients with hand eczema, it is important to ask if they have a history of atopic dermatitis, asthma, or allergic rhinitis,” said Dr. Jonas, who was not involved in the study.

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University, Cleveland, was surprised by the inverse link between physical activity and HE. 

“What struck me as interesting is the inverse association between hand eczema and physical activity, that greater physical activity will decrease the risk for hand eczema,” she said in an interview. “It’s an interesting finding that’s worth exploring.

“Dermatologists have also speculated about the association with the female gender, because women are more likely to be in situations that involve frequent hand washing or in occupations, such as hairdressing, that involve known irritants and allergens,” added Dr. Baron, who was not involved in the study.

The main weakness, she noted, is the reliance on self-reported diagnosis. “Hand eczema is a common condition, but the etiologies of reported hand eczema may vary.

“Being cognizant of these associations can help us prescribe appropriate medications and advise patients about how they can avoid exposures that will aggravate their condition,” Dr. Baron advised.

The authors recommend further related studies.

The authors, Dr. Jonas, and Dr. Baron report no relevant financial relationships. The study was not funded.

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

All atopic diseases, as well as environmental and parental factors, appear to be linked with hand eczema (HE), a longitudinal study from Finland has shown.

“In this population-based study, all atopic diseases, not only atopic dermatitis, were found as individual risk factors for HE. In addition, female gender, obesity and mold exposure increased the risk of HE,” wrote Marjut Koskelo, MD, and her colleagues at the University of Oulu in Finland. Their report was published in Contact Dermatitis.

“Parental allergy was also a risk factor of offspring’s HE. Moderate or high physical activity as well as owning a dog appeared as protective factors of HE. No association was found between other lifestyle factors and HE,” they added.

Hand eczema is one of the most common skin disorders and is the most common occupational skin disease, the authors wrote. Many risk factors, including atopic dermatitis, are known to be linked with HE, but whether various other factors might also be linked has not been well studied.

The research team investigated the link between HE and atopic diseases, parental factors, environmental factors (exposure to mold, keeping animals), and lifestyle factors (physical activity, obesity, tobacco and alcohol use).

They analyzed data of people who took part in the Northern Finland Birth Cohort 1966 Study. The data, collected since 1965, includes details about 12,055 mothers in northern Finland who were expected to deliver babies in 1966, and their 12,058 live-born children. The children have been followed over the years with questionnaires and clinical examinations, and their parents have been followed by national registers and medical reports.

For the 46-year follow-up, 6,830 respondents aged 45-46 years, roughly half of them women, completed a 132-question form covering physical health, lifestyle, environmental factors, socioeconomic status, and history of hand eczema and other atopic diseases.

In the statistical analysis, the researchers adjusted for atopic dermatitis, asthma, allergic rhinoconjunctivitis, education level, body mass index, maternal BMI, parental allergy, physical activity, living on a farm, and mold exposure and symptoms.

Of the 900 respondents who reported having had HE, 592 (65.8%) were women and 308 (34.2%) were men (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.49-2.0).
 

Various factors linked with hand eczema risk

The authors found the following:

• Atopic diseases and HE were linked: atopic dermatitis (adjusted odds ratio [aOR], 9.66; 95% CI, 8.03-11.66), asthma (aOR, 1.38; 95% CI, 1.12-1.71), and allergic rhinoconjunctivitis (aOR, 1.28; 95% CI, 1.04-1.56). Sex did not affect the link between atopic diseases and HE.
• Respondents who reported visible mold or mold odor in their apartments had higher risk for HE than did those without a history of mold exposure (OR, 1.32; 95% CI, 1.07-1.61).
• Obesity was linked with HE (OR, 3.44; 95% CI, 1.05-22.8), but smoking status, alcohol intake, and education level were not statistically significant risk factors for HE.
• Participants who reported moderate or high physical activity had lower risk for HE (OR, 0.78; 95% CI, 0.64-0.94; and OR, 0.56; 95% CI, 0.33-0.91, respectively) than those who were less active.
• Parental allergy increased risk for HE (OR, 1.98; 95% CI, 1.70-2.30); as maternal age, BMI, and menarche age increased, so did the risk for the child’s HE, but the increases were not statistically significant; and no significant links were found between maternal tobacco smoking, parental asthma, birth weight, parity, gestational age, and HE.
• Dog owners had less risk for HE than did people without a dog (OR, 0.83; 95% CI, 0.71-0.97); links between cat or farm animal owners and HE were not significant.

“There is a strong association between hand eczema and atopic diseases,” Maya Jonas, MD, clinical assistant professor of dermatology at The Ohio State University Wexner Medical Center in Columbus, told this news organization.

“When evaluating patients with hand eczema, it is important to ask if they have a history of atopic dermatitis, asthma, or allergic rhinitis,” said Dr. Jonas, who was not involved in the study.

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University, Cleveland, was surprised by the inverse link between physical activity and HE. 

“What struck me as interesting is the inverse association between hand eczema and physical activity, that greater physical activity will decrease the risk for hand eczema,” she said in an interview. “It’s an interesting finding that’s worth exploring.

“Dermatologists have also speculated about the association with the female gender, because women are more likely to be in situations that involve frequent hand washing or in occupations, such as hairdressing, that involve known irritants and allergens,” added Dr. Baron, who was not involved in the study.

The main weakness, she noted, is the reliance on self-reported diagnosis. “Hand eczema is a common condition, but the etiologies of reported hand eczema may vary.

“Being cognizant of these associations can help us prescribe appropriate medications and advise patients about how they can avoid exposures that will aggravate their condition,” Dr. Baron advised.

The authors recommend further related studies.

The authors, Dr. Jonas, and Dr. Baron report no relevant financial relationships. The study was not funded.

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

All atopic diseases, as well as environmental and parental factors, appear to be linked with hand eczema (HE), a longitudinal study from Finland has shown.

“In this population-based study, all atopic diseases, not only atopic dermatitis, were found as individual risk factors for HE. In addition, female gender, obesity and mold exposure increased the risk of HE,” wrote Marjut Koskelo, MD, and her colleagues at the University of Oulu in Finland. Their report was published in Contact Dermatitis.

“Parental allergy was also a risk factor of offspring’s HE. Moderate or high physical activity as well as owning a dog appeared as protective factors of HE. No association was found between other lifestyle factors and HE,” they added.

Hand eczema is one of the most common skin disorders and is the most common occupational skin disease, the authors wrote. Many risk factors, including atopic dermatitis, are known to be linked with HE, but whether various other factors might also be linked has not been well studied.

The research team investigated the link between HE and atopic diseases, parental factors, environmental factors (exposure to mold, keeping animals), and lifestyle factors (physical activity, obesity, tobacco and alcohol use).

They analyzed data of people who took part in the Northern Finland Birth Cohort 1966 Study. The data, collected since 1965, includes details about 12,055 mothers in northern Finland who were expected to deliver babies in 1966, and their 12,058 live-born children. The children have been followed over the years with questionnaires and clinical examinations, and their parents have been followed by national registers and medical reports.

For the 46-year follow-up, 6,830 respondents aged 45-46 years, roughly half of them women, completed a 132-question form covering physical health, lifestyle, environmental factors, socioeconomic status, and history of hand eczema and other atopic diseases.

In the statistical analysis, the researchers adjusted for atopic dermatitis, asthma, allergic rhinoconjunctivitis, education level, body mass index, maternal BMI, parental allergy, physical activity, living on a farm, and mold exposure and symptoms.

Of the 900 respondents who reported having had HE, 592 (65.8%) were women and 308 (34.2%) were men (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.49-2.0).
 

Various factors linked with hand eczema risk

The authors found the following:

• Atopic diseases and HE were linked: atopic dermatitis (adjusted odds ratio [aOR], 9.66; 95% CI, 8.03-11.66), asthma (aOR, 1.38; 95% CI, 1.12-1.71), and allergic rhinoconjunctivitis (aOR, 1.28; 95% CI, 1.04-1.56). Sex did not affect the link between atopic diseases and HE.
• Respondents who reported visible mold or mold odor in their apartments had higher risk for HE than did those without a history of mold exposure (OR, 1.32; 95% CI, 1.07-1.61).
• Obesity was linked with HE (OR, 3.44; 95% CI, 1.05-22.8), but smoking status, alcohol intake, and education level were not statistically significant risk factors for HE.
• Participants who reported moderate or high physical activity had lower risk for HE (OR, 0.78; 95% CI, 0.64-0.94; and OR, 0.56; 95% CI, 0.33-0.91, respectively) than those who were less active.
• Parental allergy increased risk for HE (OR, 1.98; 95% CI, 1.70-2.30); as maternal age, BMI, and menarche age increased, so did the risk for the child’s HE, but the increases were not statistically significant; and no significant links were found between maternal tobacco smoking, parental asthma, birth weight, parity, gestational age, and HE.
• Dog owners had less risk for HE than did people without a dog (OR, 0.83; 95% CI, 0.71-0.97); links between cat or farm animal owners and HE were not significant.

“There is a strong association between hand eczema and atopic diseases,” Maya Jonas, MD, clinical assistant professor of dermatology at The Ohio State University Wexner Medical Center in Columbus, told this news organization.

“When evaluating patients with hand eczema, it is important to ask if they have a history of atopic dermatitis, asthma, or allergic rhinitis,” said Dr. Jonas, who was not involved in the study.

Elma Baron, MD, professor and director, Skin Study Center, department of dermatology, Case Western Reserve University, Cleveland, was surprised by the inverse link between physical activity and HE. 

“What struck me as interesting is the inverse association between hand eczema and physical activity, that greater physical activity will decrease the risk for hand eczema,” she said in an interview. “It’s an interesting finding that’s worth exploring.

“Dermatologists have also speculated about the association with the female gender, because women are more likely to be in situations that involve frequent hand washing or in occupations, such as hairdressing, that involve known irritants and allergens,” added Dr. Baron, who was not involved in the study.

The main weakness, she noted, is the reliance on self-reported diagnosis. “Hand eczema is a common condition, but the etiologies of reported hand eczema may vary.

“Being cognizant of these associations can help us prescribe appropriate medications and advise patients about how they can avoid exposures that will aggravate their condition,” Dr. Baron advised.

The authors recommend further related studies.

The authors, Dr. Jonas, and Dr. Baron report no relevant financial relationships. The study was not funded.

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

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Recent study findings published in Allergy (2022 Aug 23. doi: 10.1111/all.15491) suggest that twice-daily application of emollients within the first 8 weeks of life significantly reduces the cumulative incidence of atopic dermatitis (AD) among infants at high risk for the condition, at least within the first year of life.

The single-center STOP-AD clinical trial recruited term infants within 4 days of birth who were at high risk for AD, as determined on the basis of a parent-reported history of the disease or asthma or allergic rhinitis. Infants were randomly assigned to undergo either a standard skin care routine (control group; n = 160) or twice-daily emollient application for the first 8 weeks of life (intervention group; n = 161).

In the intervention group, infants received an emollient that was specifically formulated for AD-prone skin. The control group received standard skin care advice, which did not include specific advice on bathing frequency or regular emollient use.

The mean age of the infants at randomization was 1.9 days. A total of 41 infants in the intervention group and 20 infants in the control group were withdrawn from the study. Most withdrawals (80%) occurred prior to the 2-week visit.

At 12 months, the cumulative incidence of AD was 32.8% in the intervention group and 46.4% in the control group (P = .036). The investigators note that daily emollient use was associated with a 29% lower risk of cumulative AD at 1 year in comparison with the control intervention.

No significant difference was observed between the groups regarding the incidence of parent-reported skin infections during the treatment period (5.0% vs. 5.7%; P > .05).

Study investigator Jonathan O’Brien Hourihane, MBBS, of the Royal College of Surgeons in Dublin, said in an interview that previously published findings from the BASELINE study supported the rationale for the early use of emollients in infancy to prevent AD.

The investigators of the BASELINE study found that skin barrier function, as measured by transepidermal water loss, increased from birth to 8 weeks but then became stable at 6 months. These observations suggest that the period during early infancy “could be a critical window in which to protect the skin barrier” of infants at risk for AD, Dr. Hourihane added.

Dr. Hourihane, who serves as the head of department of pediatrics at the Royal College of Surgeons, explained that the long-term clinical burden of AD is often more significant if the condition begins earlier in life, underscoring the importance of early prevention and control.

“The casual role [of AD] in other allergic conditions remains suspected but not proven, but its association is clear,” he said. He noted that infants with eczema “also have poorer sleep, and the condition causes increased family disruption,” highlighting the far-reaching burden of AD.

Commenting on the study, Adelaide Hebert, MD, professor of pediatric dermatology at the University of Texas, Houston, said in an interview that the barrier defect observed in AD is one of the prime areas to address as a means of controlling the chronic, relapsing disorder. She noted that the use of emollients can repair this defective barrier.

“Early initiation of emollients has the potential to reduce dryness, itching, transgression of allergens, and infectious agents,” explained Dr. Hebert, who wasn’t involved in the study. “Emollient application also allows the parent to inspect the skin surface and address any challenges in a timely manner.”

In the STOP-AD trial, Dr. Hourihane and colleagues also found that, among patients with loss-of-function (LoF) mutations in the filaggrin gene (FLG), the prevalence of AD at 6 and 12 months seemed to be a higher than among patients with the wild-type gene, but the difference did not reach statistical significance.

Commenting on this finding, Dr. Hebert noted that LoF FLG mutation carriers may benefit especially from emollient use, given that LoF mutations in FLG is associated with reduced production of natural moisturizing factors in the skin.

Regarding future research directions, Dr. Hourihane stated that there is a need for replication and validation of the findings in studies that include infants from different ethnic backgrounds as well as those from various social settings. These studies should also include variable treatment windows to determine both short- and longer-term effects of emollient use in this population, Dr. Hourihane explained.

Dr. Hourihane added that he and the investigators do not yet understand which aspect of the study’s program was key for reducing the incidence of AD in the first year of life. “The timing of emollient initiation, the duration of treatment, the products, or maybe just a combination of these” could be possible explanations.

The study was independently supported. Dr. Hourihand reported receiving grant funding from Aimmune Therapeutics and DBV Technologies. Dr. Hebert reported no relevant financial relationships.

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

Recent study findings published in Allergy (2022 Aug 23. doi: 10.1111/all.15491) suggest that twice-daily application of emollients within the first 8 weeks of life significantly reduces the cumulative incidence of atopic dermatitis (AD) among infants at high risk for the condition, at least within the first year of life.

The single-center STOP-AD clinical trial recruited term infants within 4 days of birth who were at high risk for AD, as determined on the basis of a parent-reported history of the disease or asthma or allergic rhinitis. Infants were randomly assigned to undergo either a standard skin care routine (control group; n = 160) or twice-daily emollient application for the first 8 weeks of life (intervention group; n = 161).

In the intervention group, infants received an emollient that was specifically formulated for AD-prone skin. The control group received standard skin care advice, which did not include specific advice on bathing frequency or regular emollient use.

The mean age of the infants at randomization was 1.9 days. A total of 41 infants in the intervention group and 20 infants in the control group were withdrawn from the study. Most withdrawals (80%) occurred prior to the 2-week visit.

At 12 months, the cumulative incidence of AD was 32.8% in the intervention group and 46.4% in the control group (P = .036). The investigators note that daily emollient use was associated with a 29% lower risk of cumulative AD at 1 year in comparison with the control intervention.

No significant difference was observed between the groups regarding the incidence of parent-reported skin infections during the treatment period (5.0% vs. 5.7%; P > .05).

Study investigator Jonathan O’Brien Hourihane, MBBS, of the Royal College of Surgeons in Dublin, said in an interview that previously published findings from the BASELINE study supported the rationale for the early use of emollients in infancy to prevent AD.

The investigators of the BASELINE study found that skin barrier function, as measured by transepidermal water loss, increased from birth to 8 weeks but then became stable at 6 months. These observations suggest that the period during early infancy “could be a critical window in which to protect the skin barrier” of infants at risk for AD, Dr. Hourihane added.

Dr. Hourihane, who serves as the head of department of pediatrics at the Royal College of Surgeons, explained that the long-term clinical burden of AD is often more significant if the condition begins earlier in life, underscoring the importance of early prevention and control.

“The casual role [of AD] in other allergic conditions remains suspected but not proven, but its association is clear,” he said. He noted that infants with eczema “also have poorer sleep, and the condition causes increased family disruption,” highlighting the far-reaching burden of AD.

Commenting on the study, Adelaide Hebert, MD, professor of pediatric dermatology at the University of Texas, Houston, said in an interview that the barrier defect observed in AD is one of the prime areas to address as a means of controlling the chronic, relapsing disorder. She noted that the use of emollients can repair this defective barrier.

“Early initiation of emollients has the potential to reduce dryness, itching, transgression of allergens, and infectious agents,” explained Dr. Hebert, who wasn’t involved in the study. “Emollient application also allows the parent to inspect the skin surface and address any challenges in a timely manner.”

In the STOP-AD trial, Dr. Hourihane and colleagues also found that, among patients with loss-of-function (LoF) mutations in the filaggrin gene (FLG), the prevalence of AD at 6 and 12 months seemed to be a higher than among patients with the wild-type gene, but the difference did not reach statistical significance.

Commenting on this finding, Dr. Hebert noted that LoF FLG mutation carriers may benefit especially from emollient use, given that LoF mutations in FLG is associated with reduced production of natural moisturizing factors in the skin.

Regarding future research directions, Dr. Hourihane stated that there is a need for replication and validation of the findings in studies that include infants from different ethnic backgrounds as well as those from various social settings. These studies should also include variable treatment windows to determine both short- and longer-term effects of emollient use in this population, Dr. Hourihane explained.

Dr. Hourihane added that he and the investigators do not yet understand which aspect of the study’s program was key for reducing the incidence of AD in the first year of life. “The timing of emollient initiation, the duration of treatment, the products, or maybe just a combination of these” could be possible explanations.

The study was independently supported. Dr. Hourihand reported receiving grant funding from Aimmune Therapeutics and DBV Technologies. Dr. Hebert reported no relevant financial relationships.

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

Recent study findings published in Allergy (2022 Aug 23. doi: 10.1111/all.15491) suggest that twice-daily application of emollients within the first 8 weeks of life significantly reduces the cumulative incidence of atopic dermatitis (AD) among infants at high risk for the condition, at least within the first year of life.

The single-center STOP-AD clinical trial recruited term infants within 4 days of birth who were at high risk for AD, as determined on the basis of a parent-reported history of the disease or asthma or allergic rhinitis. Infants were randomly assigned to undergo either a standard skin care routine (control group; n = 160) or twice-daily emollient application for the first 8 weeks of life (intervention group; n = 161).

In the intervention group, infants received an emollient that was specifically formulated for AD-prone skin. The control group received standard skin care advice, which did not include specific advice on bathing frequency or regular emollient use.

The mean age of the infants at randomization was 1.9 days. A total of 41 infants in the intervention group and 20 infants in the control group were withdrawn from the study. Most withdrawals (80%) occurred prior to the 2-week visit.

At 12 months, the cumulative incidence of AD was 32.8% in the intervention group and 46.4% in the control group (P = .036). The investigators note that daily emollient use was associated with a 29% lower risk of cumulative AD at 1 year in comparison with the control intervention.

No significant difference was observed between the groups regarding the incidence of parent-reported skin infections during the treatment period (5.0% vs. 5.7%; P > .05).

Study investigator Jonathan O’Brien Hourihane, MBBS, of the Royal College of Surgeons in Dublin, said in an interview that previously published findings from the BASELINE study supported the rationale for the early use of emollients in infancy to prevent AD.

The investigators of the BASELINE study found that skin barrier function, as measured by transepidermal water loss, increased from birth to 8 weeks but then became stable at 6 months. These observations suggest that the period during early infancy “could be a critical window in which to protect the skin barrier” of infants at risk for AD, Dr. Hourihane added.

Dr. Hourihane, who serves as the head of department of pediatrics at the Royal College of Surgeons, explained that the long-term clinical burden of AD is often more significant if the condition begins earlier in life, underscoring the importance of early prevention and control.

“The casual role [of AD] in other allergic conditions remains suspected but not proven, but its association is clear,” he said. He noted that infants with eczema “also have poorer sleep, and the condition causes increased family disruption,” highlighting the far-reaching burden of AD.

Commenting on the study, Adelaide Hebert, MD, professor of pediatric dermatology at the University of Texas, Houston, said in an interview that the barrier defect observed in AD is one of the prime areas to address as a means of controlling the chronic, relapsing disorder. She noted that the use of emollients can repair this defective barrier.

“Early initiation of emollients has the potential to reduce dryness, itching, transgression of allergens, and infectious agents,” explained Dr. Hebert, who wasn’t involved in the study. “Emollient application also allows the parent to inspect the skin surface and address any challenges in a timely manner.”

In the STOP-AD trial, Dr. Hourihane and colleagues also found that, among patients with loss-of-function (LoF) mutations in the filaggrin gene (FLG), the prevalence of AD at 6 and 12 months seemed to be a higher than among patients with the wild-type gene, but the difference did not reach statistical significance.

Commenting on this finding, Dr. Hebert noted that LoF FLG mutation carriers may benefit especially from emollient use, given that LoF mutations in FLG is associated with reduced production of natural moisturizing factors in the skin.

Regarding future research directions, Dr. Hourihane stated that there is a need for replication and validation of the findings in studies that include infants from different ethnic backgrounds as well as those from various social settings. These studies should also include variable treatment windows to determine both short- and longer-term effects of emollient use in this population, Dr. Hourihane explained.

Dr. Hourihane added that he and the investigators do not yet understand which aspect of the study’s program was key for reducing the incidence of AD in the first year of life. “The timing of emollient initiation, the duration of treatment, the products, or maybe just a combination of these” could be possible explanations.

The study was independently supported. Dr. Hourihand reported receiving grant funding from Aimmune Therapeutics and DBV Technologies. Dr. Hebert reported no relevant financial relationships.

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

The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.

Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.

Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.

Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.

Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.

All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.

The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.

Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.

Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.

Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.

Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.

All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.

The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.

Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.

Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.

Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.

Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.

All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.