MDedge Dermatology

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

TOPLINE:

Home-based phototherapy for plaque and guttate psoriasis is as effective as office-based phototherapy, according to results of the randomized Light Treatment Effectiveness study.

METHODOLOGY:

• The pragmatic, investigator-initiated, open-label, noninferiority, randomized trial compared the effectiveness of 12 weeks of treatment with narrow-band ultraviolet B phototherapy administered at home (n = 393) vs at the doctor’s office (n = 390).
• Overall, 783 patients with plaque or guttate psoriasis (mean age, 48 years; 48% women) were enrolled at 42 academic and private clinical dermatology practices in the United States from March 1, 2019, to December 4, 2023, and were followed up through June 2024. At baseline, the mean Physician Global Assessment (PGA) and the mean Dermatology Life Quality Index (DLQI) scores were 2.7 and 12.2, respectively.
• The two co-primary endpoints were a PGA score ≤ 1 indicating clear or almost clear skin and a DLQI score ≤ 5.

TAKEAWAY:

• At 12 weeks, a PGA score ≤ 1 was achieved in 32.8% of patients using home-based phototherapy and in 25.6% of those who received office-based phototherapy (P < .001).
• At 12 weeks, a DLQI score ≤ 5 was achieved in 52.4% and 33.6% of home- and office-treated patients, respectively (P < .001).
• Similar benefits were seen across all Fitzpatrick skin types.
• A higher percentage of patients were adherent to home-based (51.4%) vs office-based (15.9%) phototherapy (P < .001).

IN PRACTICE:

“These data support the use of home phototherapy as a first-line treatment option for psoriasis,” and “efforts are needed to make home and office phototherapy more available to patients,” said the study’s lead author.

SOURCE:

Joel M. Gelfand, MD, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, presented the findings at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis meeting during the annual meeting of the European Academy of Dermatology and Venereology, with simultaneous publication in JAMA Dermatology.

LIMITATIONS:

This was an open-label trial and because of its pragmatic design, outcome data were missing. The cost of the home-based phototherapy equipment used in the study was $6040.88, which was mostly covered by Medicare, but direct costs to patients may have varied depending on their insurance plan.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Daavlin provided and shipped machines for home-based phototherapy to patients at no cost. Dr. Gelfand disclosed serving as a consultant for AbbVie, Artax, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, and other companies. The full list of author disclosures can be found in the published study.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

There are 375 species of poisonous snakes, with approximately 20,000 deaths worldwide each year due to snakebites, mostly in Asia and Africa.¹ The death rate in the United States is 14 to 20 cases per year. In the United States, a variety of rattlesnakes are poisonous. There are 2 genera of rattlesnakes: Sistrurus (3 species) and Crotalus (23 species). The pygmy rattlesnake belongs to the Sistrurus miliarius species that is divided into 3 subspecies: the Carolina pigmy rattlesnake (S miliarius miliarius), the western pygmy rattlesnake (S miliarius streckeri), and the dusky pygmy rattlesnake (S miliarius barbouri).²

The western pygmy rattlesnake belongs to the Crotalidae family. The rattlesnakes in this family also are known as pit vipers. All pit vipers have common characteristics for identification: triangular head, fangs, elliptical pupils, and a heat-sensing pit between the eyes. The western pygmy rattlesnake is found in Missouri, Arkansas, Oklahoma, Kentucky, and Tennessee.¹ It is small bodied (15–20 inches)³ and grayish-brown, with a brown dorsal stripe with black blotches on its back. It is found in glades, second-growth forests near rock ledges, and areas where powerlines cut through dense forest.³ Its venom is hemorrhagic, causing tissue damage, but does not contain neurotoxins.⁴ Bites from the western pygmy rattlesnake often do not lead to death, but the venom, which contains numerous proteins and enzymes, does cause necrotic hemorrhagic ulceration at the site of envenomation and possible loss of digit.^5,6

We present a case of a man who was bitten on the right third digit by a western pygmy rattlesnake. We describe the clinical course and treatment.

Case Report

A 56-year-old right-handed man presented to the emergency department with a rapidly swelling, painful hand following a snakebite to the dorsal aspect of the right third digit (Figure 1). He was able to capture a photograph of the snake at the time of injury, which helped identify it as a western pygmy rattlesnake (Figure 2). He also photographed the hand immediately after the bite occurred (Figure 3). Vitals on presentation included an elevated blood pressure of 161/100 mm Hg; no fever (temperature, 36.4 °C); and normal pulse oximetry of 98%, pulse of 86 beats per minute, and respiratory rate of 16 breaths per minute.

After the snakebite, the patient’s family called the Missouri Poison Center immediately. The family identified the snake species and shared this information with the poison center. Poison control recommended calling the nearest hospitals to determine if antivenom was available and make notification of arrival. 

The patient’s tetanus toxoid immunization was updated immediately upon arrival. The hand was marked to monitor swelling. Initial laboratory test results revealed the following values: sodium, 133 mmol/L (reference range, 136–145 mmol/L); potassium, 3.4 mmol/L (3.6–5.2 mmol/L); lactic acid, 2.4 mmol/L (0.5–2.2 mmol/L); creatine kinase, 425 U/L (55–170 U/L); platelet count, 68/µL (150,000–450,000/µL); fibrinogen, 169 mg/dL (185–410 mg/dL); and glucose, 121 mg/dL (74–106 mg/dL). The remainder of the complete blood cell count and metabolic panel was unremarkable. Radiographs of the hand did not show any fractures, dislocations, or foreign bodies. Missouri Poison Center was consulted. Given the patient’s severe pain, edema beyond 40 cm, and developing ecchymosis on the inner arm, the bite was graded as a 3 on the traditional snakebite severity scale. Poison control recommended 4 to 6 vials of antivenom over 60 minutes. Six vials of Crotalidae polyvalent immune fab antivenom were given.

The patient’s complete blood cell count remained unremarkable throughout his admission. His metabolic panel returned to normal at 6 hours postadmission: sodium, 139 mmol/L; potassium, 4.0 mmol/L. His lactate and creatinine kinase were not rechecked. His fibrinogen was trending upward. Serial laboratory test results revealed fibrinogen levels of 153, 158, 161, 159, 173, and 216 mg/dL at 6, 12, 18, 24, 30, and 36 hours, respectively. Other laboratory test results including prothrombin time (11.0 s) and international normalized ratio (0.98) remained within reference range (11–13 s and 0.80–1.39, respectively) during serial monitoring.

The patient was hospitalized for 40 hours while waiting for his fibrinogen level to normalize. The local skin necrosis worsened acutely in this 40-hour window (Figure 4). Intravenous antibiotics were not administered during the hospital stay. Before discharge, the patient was evaluated by the surgery service, who did not recommend debridement.

Surgical Management of Snakebites

The surgeon’s role in managing snakebites is controversial. Snakebites were once perceived as a surgical emergency due to symptoms mimicking compartment syndrome; however, snakebites rarely cause a true compartment syndrome.⁷ Prophylactic bite excision and fasciotomies are not recommended. Incision and suction of the fang marks may be beneficial if performed within 15 to 30 minutes from the time of the bite.⁸ With access to a surgeon in this short time period being nearly impossible, incision and suctioning of fang marks generally is not recommended.⁹ Retained snake fangs are a possibility, and the infection could spread to a nearby joint, causing septic arthritis,¹⁰ which would be an indication for surgical intervention. Bites to the finger often cause major swelling, and the benefits of dermotomy are documented.¹¹ Generally, early administration of antivenom will decrease local tissue reaction and prevent additional tissue loss.¹² In our patient, the decision to perform dermotomy was made when the area of necrosis had declared itself and the skin reached its elastic limit. Bozkurt et al¹³ described the neurovascular bundles within the digit as functioning as small compartments. When the skin of the digit reaches its elastic limit, pressure within the compartment may exceed the capillary closing pressure, and the integrity of small vessels and nerves may be compromised. Our case highlights the benefit of dermotomy as well as the functional and cosmetic results that can be achieved.

Wound Care for Snakebites

There is little published on the treatment of snakebites after patients are stabilized medically for hospital discharge. Venomous snakes inject toxins that predominantly consist of enzymes (eg, phospholipase A2, phosphodiesterase, hyaluronidase, peptidase, metalloproteinase) that cause tissue destruction through diverse mechanisms.¹⁴ The venom of western pygmy rattlesnakes is hemotoxic and can cause necrotic hemorrhagic ulceration,⁴ as was the case in our patient.

Silver sulfadiazine commonly is used to prevent infection in burn patients. Given the large surface area of exposed dermis after debridement and concern for infection, silver sulfadiazine was chosen in our patient for local wound care treatment. Silver sulfadiazine is a widely available and low-cost drug.¹⁵ Its antibacterial effects are due to the silver ions, which only act superficially and therefore limit systemic absorption.¹⁶ Application should be performed in a clean manner with minimal trauma to the tissue. This technique is best achieved by using sterile gloves and applying the medication manually. A 0.0625-inch layer should be applied to entirely cover the cleaned debrided area.¹⁷ When performing application with tongue blades or cotton swabs, it is important to never “double dip.” Patient education on proper administration is imperative to a successful outcome.

Final Thoughts

Our case demonstrates the safe use of Crotalidae polyvalent immune fab antivenom for the treatment of western pygmy rattlesnake (S miliarius streckeri) envenomation. Early administration of antivenom following pit viper rattlesnake envenomations is important to mitigate systemic effects and the extent of soft tissue damage. There are few studies on local wound care treatment after rattlesnake envenomation. This case highlights the role of dermotomy and wound care with silver sulfadiazine cream 1%.

There are 375 species of poisonous snakes, with approximately 20,000 deaths worldwide each year due to snakebites, mostly in Asia and Africa.¹ The death rate in the United States is 14 to 20 cases per year. In the United States, a variety of rattlesnakes are poisonous. There are 2 genera of rattlesnakes: Sistrurus (3 species) and Crotalus (23 species). The pygmy rattlesnake belongs to the Sistrurus miliarius species that is divided into 3 subspecies: the Carolina pigmy rattlesnake (S miliarius miliarius), the western pygmy rattlesnake (S miliarius streckeri), and the dusky pygmy rattlesnake (S miliarius barbouri).²

The western pygmy rattlesnake belongs to the Crotalidae family. The rattlesnakes in this family also are known as pit vipers. All pit vipers have common characteristics for identification: triangular head, fangs, elliptical pupils, and a heat-sensing pit between the eyes. The western pygmy rattlesnake is found in Missouri, Arkansas, Oklahoma, Kentucky, and Tennessee.¹ It is small bodied (15–20 inches)³ and grayish-brown, with a brown dorsal stripe with black blotches on its back. It is found in glades, second-growth forests near rock ledges, and areas where powerlines cut through dense forest.³ Its venom is hemorrhagic, causing tissue damage, but does not contain neurotoxins.⁴ Bites from the western pygmy rattlesnake often do not lead to death, but the venom, which contains numerous proteins and enzymes, does cause necrotic hemorrhagic ulceration at the site of envenomation and possible loss of digit.^5,6

We present a case of a man who was bitten on the right third digit by a western pygmy rattlesnake. We describe the clinical course and treatment.

Case Report

A 56-year-old right-handed man presented to the emergency department with a rapidly swelling, painful hand following a snakebite to the dorsal aspect of the right third digit (Figure 1). He was able to capture a photograph of the snake at the time of injury, which helped identify it as a western pygmy rattlesnake (Figure 2). He also photographed the hand immediately after the bite occurred (Figure 3). Vitals on presentation included an elevated blood pressure of 161/100 mm Hg; no fever (temperature, 36.4 °C); and normal pulse oximetry of 98%, pulse of 86 beats per minute, and respiratory rate of 16 breaths per minute.

After the snakebite, the patient’s family called the Missouri Poison Center immediately. The family identified the snake species and shared this information with the poison center. Poison control recommended calling the nearest hospitals to determine if antivenom was available and make notification of arrival. 

The patient’s tetanus toxoid immunization was updated immediately upon arrival. The hand was marked to monitor swelling. Initial laboratory test results revealed the following values: sodium, 133 mmol/L (reference range, 136–145 mmol/L); potassium, 3.4 mmol/L (3.6–5.2 mmol/L); lactic acid, 2.4 mmol/L (0.5–2.2 mmol/L); creatine kinase, 425 U/L (55–170 U/L); platelet count, 68/µL (150,000–450,000/µL); fibrinogen, 169 mg/dL (185–410 mg/dL); and glucose, 121 mg/dL (74–106 mg/dL). The remainder of the complete blood cell count and metabolic panel was unremarkable. Radiographs of the hand did not show any fractures, dislocations, or foreign bodies. Missouri Poison Center was consulted. Given the patient’s severe pain, edema beyond 40 cm, and developing ecchymosis on the inner arm, the bite was graded as a 3 on the traditional snakebite severity scale. Poison control recommended 4 to 6 vials of antivenom over 60 minutes. Six vials of Crotalidae polyvalent immune fab antivenom were given.

The patient’s complete blood cell count remained unremarkable throughout his admission. His metabolic panel returned to normal at 6 hours postadmission: sodium, 139 mmol/L; potassium, 4.0 mmol/L. His lactate and creatinine kinase were not rechecked. His fibrinogen was trending upward. Serial laboratory test results revealed fibrinogen levels of 153, 158, 161, 159, 173, and 216 mg/dL at 6, 12, 18, 24, 30, and 36 hours, respectively. Other laboratory test results including prothrombin time (11.0 s) and international normalized ratio (0.98) remained within reference range (11–13 s and 0.80–1.39, respectively) during serial monitoring.

The patient was hospitalized for 40 hours while waiting for his fibrinogen level to normalize. The local skin necrosis worsened acutely in this 40-hour window (Figure 4). Intravenous antibiotics were not administered during the hospital stay. Before discharge, the patient was evaluated by the surgery service, who did not recommend debridement.

Surgical Management of Snakebites

The surgeon’s role in managing snakebites is controversial. Snakebites were once perceived as a surgical emergency due to symptoms mimicking compartment syndrome; however, snakebites rarely cause a true compartment syndrome.⁷ Prophylactic bite excision and fasciotomies are not recommended. Incision and suction of the fang marks may be beneficial if performed within 15 to 30 minutes from the time of the bite.⁸ With access to a surgeon in this short time period being nearly impossible, incision and suctioning of fang marks generally is not recommended.⁹ Retained snake fangs are a possibility, and the infection could spread to a nearby joint, causing septic arthritis,¹⁰ which would be an indication for surgical intervention. Bites to the finger often cause major swelling, and the benefits of dermotomy are documented.¹¹ Generally, early administration of antivenom will decrease local tissue reaction and prevent additional tissue loss.¹² In our patient, the decision to perform dermotomy was made when the area of necrosis had declared itself and the skin reached its elastic limit. Bozkurt et al¹³ described the neurovascular bundles within the digit as functioning as small compartments. When the skin of the digit reaches its elastic limit, pressure within the compartment may exceed the capillary closing pressure, and the integrity of small vessels and nerves may be compromised. Our case highlights the benefit of dermotomy as well as the functional and cosmetic results that can be achieved.

Wound Care for Snakebites

There is little published on the treatment of snakebites after patients are stabilized medically for hospital discharge. Venomous snakes inject toxins that predominantly consist of enzymes (eg, phospholipase A2, phosphodiesterase, hyaluronidase, peptidase, metalloproteinase) that cause tissue destruction through diverse mechanisms.¹⁴ The venom of western pygmy rattlesnakes is hemotoxic and can cause necrotic hemorrhagic ulceration,⁴ as was the case in our patient.

Silver sulfadiazine commonly is used to prevent infection in burn patients. Given the large surface area of exposed dermis after debridement and concern for infection, silver sulfadiazine was chosen in our patient for local wound care treatment. Silver sulfadiazine is a widely available and low-cost drug.¹⁵ Its antibacterial effects are due to the silver ions, which only act superficially and therefore limit systemic absorption.¹⁶ Application should be performed in a clean manner with minimal trauma to the tissue. This technique is best achieved by using sterile gloves and applying the medication manually. A 0.0625-inch layer should be applied to entirely cover the cleaned debrided area.¹⁷ When performing application with tongue blades or cotton swabs, it is important to never “double dip.” Patient education on proper administration is imperative to a successful outcome.

Final Thoughts

Our case demonstrates the safe use of Crotalidae polyvalent immune fab antivenom for the treatment of western pygmy rattlesnake (S miliarius streckeri) envenomation. Early administration of antivenom following pit viper rattlesnake envenomations is important to mitigate systemic effects and the extent of soft tissue damage. There are few studies on local wound care treatment after rattlesnake envenomation. This case highlights the role of dermotomy and wound care with silver sulfadiazine cream 1%.

There are 375 species of poisonous snakes, with approximately 20,000 deaths worldwide each year due to snakebites, mostly in Asia and Africa.¹ The death rate in the United States is 14 to 20 cases per year. In the United States, a variety of rattlesnakes are poisonous. There are 2 genera of rattlesnakes: Sistrurus (3 species) and Crotalus (23 species). The pygmy rattlesnake belongs to the Sistrurus miliarius species that is divided into 3 subspecies: the Carolina pigmy rattlesnake (S miliarius miliarius), the western pygmy rattlesnake (S miliarius streckeri), and the dusky pygmy rattlesnake (S miliarius barbouri).²

The western pygmy rattlesnake belongs to the Crotalidae family. The rattlesnakes in this family also are known as pit vipers. All pit vipers have common characteristics for identification: triangular head, fangs, elliptical pupils, and a heat-sensing pit between the eyes. The western pygmy rattlesnake is found in Missouri, Arkansas, Oklahoma, Kentucky, and Tennessee.¹ It is small bodied (15–20 inches)³ and grayish-brown, with a brown dorsal stripe with black blotches on its back. It is found in glades, second-growth forests near rock ledges, and areas where powerlines cut through dense forest.³ Its venom is hemorrhagic, causing tissue damage, but does not contain neurotoxins.⁴ Bites from the western pygmy rattlesnake often do not lead to death, but the venom, which contains numerous proteins and enzymes, does cause necrotic hemorrhagic ulceration at the site of envenomation and possible loss of digit.^5,6

We present a case of a man who was bitten on the right third digit by a western pygmy rattlesnake. We describe the clinical course and treatment.

Case Report

A 56-year-old right-handed man presented to the emergency department with a rapidly swelling, painful hand following a snakebite to the dorsal aspect of the right third digit (Figure 1). He was able to capture a photograph of the snake at the time of injury, which helped identify it as a western pygmy rattlesnake (Figure 2). He also photographed the hand immediately after the bite occurred (Figure 3). Vitals on presentation included an elevated blood pressure of 161/100 mm Hg; no fever (temperature, 36.4 °C); and normal pulse oximetry of 98%, pulse of 86 beats per minute, and respiratory rate of 16 breaths per minute.

After the snakebite, the patient’s family called the Missouri Poison Center immediately. The family identified the snake species and shared this information with the poison center. Poison control recommended calling the nearest hospitals to determine if antivenom was available and make notification of arrival. 

The patient’s tetanus toxoid immunization was updated immediately upon arrival. The hand was marked to monitor swelling. Initial laboratory test results revealed the following values: sodium, 133 mmol/L (reference range, 136–145 mmol/L); potassium, 3.4 mmol/L (3.6–5.2 mmol/L); lactic acid, 2.4 mmol/L (0.5–2.2 mmol/L); creatine kinase, 425 U/L (55–170 U/L); platelet count, 68/µL (150,000–450,000/µL); fibrinogen, 169 mg/dL (185–410 mg/dL); and glucose, 121 mg/dL (74–106 mg/dL). The remainder of the complete blood cell count and metabolic panel was unremarkable. Radiographs of the hand did not show any fractures, dislocations, or foreign bodies. Missouri Poison Center was consulted. Given the patient’s severe pain, edema beyond 40 cm, and developing ecchymosis on the inner arm, the bite was graded as a 3 on the traditional snakebite severity scale. Poison control recommended 4 to 6 vials of antivenom over 60 minutes. Six vials of Crotalidae polyvalent immune fab antivenom were given.

The patient’s complete blood cell count remained unremarkable throughout his admission. His metabolic panel returned to normal at 6 hours postadmission: sodium, 139 mmol/L; potassium, 4.0 mmol/L. His lactate and creatinine kinase were not rechecked. His fibrinogen was trending upward. Serial laboratory test results revealed fibrinogen levels of 153, 158, 161, 159, 173, and 216 mg/dL at 6, 12, 18, 24, 30, and 36 hours, respectively. Other laboratory test results including prothrombin time (11.0 s) and international normalized ratio (0.98) remained within reference range (11–13 s and 0.80–1.39, respectively) during serial monitoring.

The patient was hospitalized for 40 hours while waiting for his fibrinogen level to normalize. The local skin necrosis worsened acutely in this 40-hour window (Figure 4). Intravenous antibiotics were not administered during the hospital stay. Before discharge, the patient was evaluated by the surgery service, who did not recommend debridement.

Surgical Management of Snakebites

The surgeon’s role in managing snakebites is controversial. Snakebites were once perceived as a surgical emergency due to symptoms mimicking compartment syndrome; however, snakebites rarely cause a true compartment syndrome.⁷ Prophylactic bite excision and fasciotomies are not recommended. Incision and suction of the fang marks may be beneficial if performed within 15 to 30 minutes from the time of the bite.⁸ With access to a surgeon in this short time period being nearly impossible, incision and suctioning of fang marks generally is not recommended.⁹ Retained snake fangs are a possibility, and the infection could spread to a nearby joint, causing septic arthritis,¹⁰ which would be an indication for surgical intervention. Bites to the finger often cause major swelling, and the benefits of dermotomy are documented.¹¹ Generally, early administration of antivenom will decrease local tissue reaction and prevent additional tissue loss.¹² In our patient, the decision to perform dermotomy was made when the area of necrosis had declared itself and the skin reached its elastic limit. Bozkurt et al¹³ described the neurovascular bundles within the digit as functioning as small compartments. When the skin of the digit reaches its elastic limit, pressure within the compartment may exceed the capillary closing pressure, and the integrity of small vessels and nerves may be compromised. Our case highlights the benefit of dermotomy as well as the functional and cosmetic results that can be achieved.

Wound Care for Snakebites

There is little published on the treatment of snakebites after patients are stabilized medically for hospital discharge. Venomous snakes inject toxins that predominantly consist of enzymes (eg, phospholipase A2, phosphodiesterase, hyaluronidase, peptidase, metalloproteinase) that cause tissue destruction through diverse mechanisms.¹⁴ The venom of western pygmy rattlesnakes is hemotoxic and can cause necrotic hemorrhagic ulceration,⁴ as was the case in our patient.

Silver sulfadiazine commonly is used to prevent infection in burn patients. Given the large surface area of exposed dermis after debridement and concern for infection, silver sulfadiazine was chosen in our patient for local wound care treatment. Silver sulfadiazine is a widely available and low-cost drug.¹⁵ Its antibacterial effects are due to the silver ions, which only act superficially and therefore limit systemic absorption.¹⁶ Application should be performed in a clean manner with minimal trauma to the tissue. This technique is best achieved by using sterile gloves and applying the medication manually. A 0.0625-inch layer should be applied to entirely cover the cleaned debrided area.¹⁷ When performing application with tongue blades or cotton swabs, it is important to never “double dip.” Patient education on proper administration is imperative to a successful outcome.

Final Thoughts

Our case demonstrates the safe use of Crotalidae polyvalent immune fab antivenom for the treatment of western pygmy rattlesnake (S miliarius streckeri) envenomation. Early administration of antivenom following pit viper rattlesnake envenomations is important to mitigate systemic effects and the extent of soft tissue damage. There are few studies on local wound care treatment after rattlesnake envenomation. This case highlights the role of dermotomy and wound care with silver sulfadiazine cream 1%.

THE DIAGNOSIS: Papular Acantholytic Dyskeratosis

Histopathology of the lesion in our patient revealed hyperkeratosis, parakeratosis, dyskeratosis, and acantholysis of keratinocytes. The dermis showed variable chronic inflammatory cells. Corps ronds and grains in the acantholytic layer of the epidermis were identified. Hair follicles were not affected by acantholysis. Anti–desmoglein 1 and anti–desmoglein 3 serum antibodies were negative. Based on the combined clinical and histologic findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD) of the genitocrural area.

Although its typical histopathologic pattern mimics both Hailey-Hailey disease and Darier disease, PAD is a rare unique clinicopathologic entity recognized by dermatopathologists. It usually occurs in middle-aged women with no family history of similar conditions. The multiple localized, flesh-colored to whitish papules of PAD tend to coalesce into plaques in the anogenital and genitocrural regions. Plaques usually are asymptomatic but may be pruritic. Histopathologically, PAD will demonstrate hyperkeratosis, dyskeratosis, and acantholysis. Corps ronds and grains will be present in the acantholytic layer of the epidermis.^1,2

The differential diagnosis for PAD includes pemphigus vegetans, Hailey-Hailey disease, Darier disease, and Grover disease. Patients usually develop pemphigus vegetans at an older age (typically 50–70 years).³ Histopathologically, it is characterized by pseudoepitheliomatous hyperplasia with an eosinophilic microabscess as well as acantholysis that involves the follicular epithelium (Figure 1),⁴ which were not seen in our patient. Direct immunofluorescence will show the intercellular pattern of the pemphigus group, and antidesmoglein antibodies can be detected by enzyme-linked immunosorbent assay.^4,5

Hailey-Hailey disease (also known as benign familial pemphigus) typically manifests as itchy malodorous vesicles and erosions, especially in intertriginous areas. The most commonly affected sites are the groin, neck, under the breasts, and between the buttocks. In one study, two-thirds of affected patients reported a relevant family history.⁴ Histopathology will show minimal dyskeratosis and suprabasilar acantholysis with loss of intercellular bridges, classically described as resembling a dilapidated brick wall (Figure 2).^4,5 There is no notable follicular involvement with acantholysis.⁴

Darier disease (also known as keratosis follicularis) typically is inherited in an autosomal-dominant pattern.⁴ It is found on the seborrheic areas such as the scalp, forehead, nasolabial folds, and upper chest. Characteristic features include distal notching of the nails, mucosal lesions, and palmoplantar papules. Histopathology will reveal acantholysis, dyskeratosis, suprabasilar acantholysis, and corps ronds and grains.⁴ Acantholysis in Darier disease can be in discrete foci and/or widespread (Figure 3).⁴ Darier disease demonstrates more dyskeratosis than Hailey-Hailey disease.^4,5

Grover disease (also referred to as transient acantholytic dermatosis) is observed predominantly in individuals who are middle-aged or older, though occurrence in children has been rarely reported.⁴ It affects the trunk, neck, and proximal limbs but spares the genital area. Histopathology may reveal acantholysis (similar to Hailey-Hailey disease or pemphigus vulgaris), dyskeratosis (resembling Darier disease), spongiosis, parakeratosis, and a superficial perivascular lymphocytic infiltrate with eosinophils.⁴ A histologic clue to the diagnosis is small lesion size (1–3 mm). Usually, only 1 or 2 small discrete lesions that span a few rete ridges are noted (Figure 4).⁴ Grover disease can cause follicular or acrosyringeal involvement.⁴

THE DIAGNOSIS: Papular Acantholytic Dyskeratosis

Histopathology of the lesion in our patient revealed hyperkeratosis, parakeratosis, dyskeratosis, and acantholysis of keratinocytes. The dermis showed variable chronic inflammatory cells. Corps ronds and grains in the acantholytic layer of the epidermis were identified. Hair follicles were not affected by acantholysis. Anti–desmoglein 1 and anti–desmoglein 3 serum antibodies were negative. Based on the combined clinical and histologic findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD) of the genitocrural area.

Although its typical histopathologic pattern mimics both Hailey-Hailey disease and Darier disease, PAD is a rare unique clinicopathologic entity recognized by dermatopathologists. It usually occurs in middle-aged women with no family history of similar conditions. The multiple localized, flesh-colored to whitish papules of PAD tend to coalesce into plaques in the anogenital and genitocrural regions. Plaques usually are asymptomatic but may be pruritic. Histopathologically, PAD will demonstrate hyperkeratosis, dyskeratosis, and acantholysis. Corps ronds and grains will be present in the acantholytic layer of the epidermis.^1,2

The differential diagnosis for PAD includes pemphigus vegetans, Hailey-Hailey disease, Darier disease, and Grover disease. Patients usually develop pemphigus vegetans at an older age (typically 50–70 years).³ Histopathologically, it is characterized by pseudoepitheliomatous hyperplasia with an eosinophilic microabscess as well as acantholysis that involves the follicular epithelium (Figure 1),⁴ which were not seen in our patient. Direct immunofluorescence will show the intercellular pattern of the pemphigus group, and antidesmoglein antibodies can be detected by enzyme-linked immunosorbent assay.^4,5

Hailey-Hailey disease (also known as benign familial pemphigus) typically manifests as itchy malodorous vesicles and erosions, especially in intertriginous areas. The most commonly affected sites are the groin, neck, under the breasts, and between the buttocks. In one study, two-thirds of affected patients reported a relevant family history.⁴ Histopathology will show minimal dyskeratosis and suprabasilar acantholysis with loss of intercellular bridges, classically described as resembling a dilapidated brick wall (Figure 2).^4,5 There is no notable follicular involvement with acantholysis.⁴

Darier disease (also known as keratosis follicularis) typically is inherited in an autosomal-dominant pattern.⁴ It is found on the seborrheic areas such as the scalp, forehead, nasolabial folds, and upper chest. Characteristic features include distal notching of the nails, mucosal lesions, and palmoplantar papules. Histopathology will reveal acantholysis, dyskeratosis, suprabasilar acantholysis, and corps ronds and grains.⁴ Acantholysis in Darier disease can be in discrete foci and/or widespread (Figure 3).⁴ Darier disease demonstrates more dyskeratosis than Hailey-Hailey disease.^4,5

Grover disease (also referred to as transient acantholytic dermatosis) is observed predominantly in individuals who are middle-aged or older, though occurrence in children has been rarely reported.⁴ It affects the trunk, neck, and proximal limbs but spares the genital area. Histopathology may reveal acantholysis (similar to Hailey-Hailey disease or pemphigus vulgaris), dyskeratosis (resembling Darier disease), spongiosis, parakeratosis, and a superficial perivascular lymphocytic infiltrate with eosinophils.⁴ A histologic clue to the diagnosis is small lesion size (1–3 mm). Usually, only 1 or 2 small discrete lesions that span a few rete ridges are noted (Figure 4).⁴ Grover disease can cause follicular or acrosyringeal involvement.⁴

THE DIAGNOSIS: Papular Acantholytic Dyskeratosis

Histopathology of the lesion in our patient revealed hyperkeratosis, parakeratosis, dyskeratosis, and acantholysis of keratinocytes. The dermis showed variable chronic inflammatory cells. Corps ronds and grains in the acantholytic layer of the epidermis were identified. Hair follicles were not affected by acantholysis. Anti–desmoglein 1 and anti–desmoglein 3 serum antibodies were negative. Based on the combined clinical and histologic findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD) of the genitocrural area.

Although its typical histopathologic pattern mimics both Hailey-Hailey disease and Darier disease, PAD is a rare unique clinicopathologic entity recognized by dermatopathologists. It usually occurs in middle-aged women with no family history of similar conditions. The multiple localized, flesh-colored to whitish papules of PAD tend to coalesce into plaques in the anogenital and genitocrural regions. Plaques usually are asymptomatic but may be pruritic. Histopathologically, PAD will demonstrate hyperkeratosis, dyskeratosis, and acantholysis. Corps ronds and grains will be present in the acantholytic layer of the epidermis.^1,2

The differential diagnosis for PAD includes pemphigus vegetans, Hailey-Hailey disease, Darier disease, and Grover disease. Patients usually develop pemphigus vegetans at an older age (typically 50–70 years).³ Histopathologically, it is characterized by pseudoepitheliomatous hyperplasia with an eosinophilic microabscess as well as acantholysis that involves the follicular epithelium (Figure 1),⁴ which were not seen in our patient. Direct immunofluorescence will show the intercellular pattern of the pemphigus group, and antidesmoglein antibodies can be detected by enzyme-linked immunosorbent assay.^4,5

Hailey-Hailey disease (also known as benign familial pemphigus) typically manifests as itchy malodorous vesicles and erosions, especially in intertriginous areas. The most commonly affected sites are the groin, neck, under the breasts, and between the buttocks. In one study, two-thirds of affected patients reported a relevant family history.⁴ Histopathology will show minimal dyskeratosis and suprabasilar acantholysis with loss of intercellular bridges, classically described as resembling a dilapidated brick wall (Figure 2).^4,5 There is no notable follicular involvement with acantholysis.⁴

Darier disease (also known as keratosis follicularis) typically is inherited in an autosomal-dominant pattern.⁴ It is found on the seborrheic areas such as the scalp, forehead, nasolabial folds, and upper chest. Characteristic features include distal notching of the nails, mucosal lesions, and palmoplantar papules. Histopathology will reveal acantholysis, dyskeratosis, suprabasilar acantholysis, and corps ronds and grains.⁴ Acantholysis in Darier disease can be in discrete foci and/or widespread (Figure 3).⁴ Darier disease demonstrates more dyskeratosis than Hailey-Hailey disease.^4,5

Grover disease (also referred to as transient acantholytic dermatosis) is observed predominantly in individuals who are middle-aged or older, though occurrence in children has been rarely reported.⁴ It affects the trunk, neck, and proximal limbs but spares the genital area. Histopathology may reveal acantholysis (similar to Hailey-Hailey disease or pemphigus vulgaris), dyskeratosis (resembling Darier disease), spongiosis, parakeratosis, and a superficial perivascular lymphocytic infiltrate with eosinophils.⁴ A histologic clue to the diagnosis is small lesion size (1–3 mm). Usually, only 1 or 2 small discrete lesions that span a few rete ridges are noted (Figure 4).⁴ Grover disease can cause follicular or acrosyringeal involvement.⁴

To the Editor:

Skin cancers are extremely common worldwide. Malignant melanomas comprise approximately 1 in 5 of these cancers. Exposure to UV radiation is postulated to be responsible for a global rise in melanoma cases over the past 50 years.¹ Pediatric melanoma is a particularly rare condition that affects approximately 6 in every 1 million children.² Melanoma incidence in children ranges by age, increasing by approximately 10-fold from age 1 to 4 years to age 15 to 19 years. Tumor ulceration is a feature more commonly seen among children younger than 10 years and is associated with worse outcomes. Tumor thickness and ulceration strongly predict sentinel lymph node metastases among children, which also is associated with a poor prognosis.³

A recent study evaluating stage IV melanoma survival rates in adolescents and young adults (AYAs) vs older adults found that survival is much worse among AYAs. Thicker tumors and public health insurance also were associated with worse survival rates for AYAs, while early detection was associated with better survival rates.⁴

Health disparities and their role in the prognosis of pediatric melanoma is another important factor. One study analyzed this relationship at the state level using Texas Cancer Registry data (1995-2009).⁵ Patients’ socioeconomic status (SES) and driving distance to the nearest pediatric cancer care center were included in the analysis. Hispanic children were found to be 3 times more likely to present with advanced disease than non-Hispanic White children. Although SES and distance to the nearest treatment center were not found to affect the melanoma stage at presentation, Hispanic ethnicity or being in the lowest SES quartile were correlated with a higher mortality risk.⁵

When considering specific subtypes of melanoma, acral lentiginous melanoma (ALM) is known to develop in patients with skin of color. A 2023 study by Holman et al⁶ reported that the percentage of melanomas that were ALMs ranged from 0.8% in non-Hispanic White individuals to 19.1% in Hispanic Black, American Indian/Alaska Native, and Asian/Pacific Islander individuals. However, ALM is rare in children. In a pooled cohort study with patient information retrieved from the nationwide Dutch Pathology Registry, only 1 child and 1 adolescent were found to have ALM across a total of 514 patients.⁷ We sought to analyze pediatric melanoma outcomes based on race and other barriers to appropriate care.

We conducted a search of the Surveillance, Epidemiology, and End Results (SEER) database from January 1995 to December 2016 for patients aged 21 years and younger with a primary melanoma diagnosis. The primary outcome was the 5-year survival rate. County-level SES variables were used to calculate a prosperity index. Kaplan-Meier analysis and Cox proportional hazards model were used to compare 5-year survival rates among the different racial/ethnic groups.

A sample of 2742 patients was identified during the study period and followed for 5 years. Eighty-two percent were White, 6% Hispanic, 2% Asian, 1% Black, and 5% classified as other/unknown race (data were missing for 4%). The cohort was predominantly female (61%). White patients were more likely to present with localized disease than any other race/ethnicity (83% vs 65% in Hispanic, 60% in Asian/Pacific Islander, and 45% in Black patients [P<.05]).

Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis. On multivariate analysis, this finding remained significant for Hispanic patients when compared with White patients (hazard ratio, 2.37 [P<.05]). Increasing age, male sex, advanced stage at diagnosis, and failure to receive surgery were associated with increased odds of mortality.

Patients with regionalized and disseminated disease had increased odds of mortality (6.16 and 64.45, respectively; P<.05) compared with patients with localized disease. Socioeconomic status and urbanization were not found to influence 5-year survival rates.

Pediatric melanoma often presents a clinical challenge with special considerations. Pediatric-specific predisposing risk factors for melanoma and an atypical clinical presentation are some of the major concerns that necessitate a tailored approach to this malignancy, especially among different age groups, skin types, and racial and socioeconomic groups.⁵ 

Standard ABCDE criteria often are inadequate for accurate detection of pediatric melanomas. Initial lesions often manifest as raised, red, amelanotic lesions mimicking pyogenic granulomas. Lesions tend to be very small (<6 mm in diameter) and can be uniform in color, thereby making the melanoma more difficult to detect compared to the characteristic findings in adults.⁵ Bleeding or ulceration often can be a warning sign during physical examination.

With regard to incidence, pediatric melanoma is relatively rare. Since the 1970s, the incidence of pediatric melanoma has been increasing; however, a recent analysis of the SEER database showed a decreasing trend from 2000 to 2010.⁴

Our analysis of the SEER data showed an increased risk for pediatric melanoma in older adolescents. In addition, the incidence of pediatric melanoma was higher in females of all racial groups except Asian/Pacific Islander individuals. However, SES was not found to significantly influence the 5-year survival rate in pediatric melanoma.

White pediatric patients were more likely to present with localized disease compared with other races. Pediatric melanoma patients with regional disease had a 6-fold increase in mortality rate vs those with localized disease; those with disseminated disease had a 65-fold higher risk. Consistent with this, Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis.

These findings suggest a relationship between race, melanoma spread, and disease severity. Patient education programs need to be directed specifically to minority groups to improve their knowledge on evolving skin lesions and sun protection practices. Physicians also need to have heightened suspicion and better knowledge of the unique traits of pediatric melanoma.⁵ 

Given the considerable influence these disparities can have on melanoma outcomes, further research is needed to characterize outcomes based on race and determine obstacles to appropriate care. Improved public outreach initiatives that accommodate specific cultural barriers (eg, language, traditional patterns of behavior) also are required to improve current circumstances.

To the Editor:

Skin cancers are extremely common worldwide. Malignant melanomas comprise approximately 1 in 5 of these cancers. Exposure to UV radiation is postulated to be responsible for a global rise in melanoma cases over the past 50 years.¹ Pediatric melanoma is a particularly rare condition that affects approximately 6 in every 1 million children.² Melanoma incidence in children ranges by age, increasing by approximately 10-fold from age 1 to 4 years to age 15 to 19 years. Tumor ulceration is a feature more commonly seen among children younger than 10 years and is associated with worse outcomes. Tumor thickness and ulceration strongly predict sentinel lymph node metastases among children, which also is associated with a poor prognosis.³

A recent study evaluating stage IV melanoma survival rates in adolescents and young adults (AYAs) vs older adults found that survival is much worse among AYAs. Thicker tumors and public health insurance also were associated with worse survival rates for AYAs, while early detection was associated with better survival rates.⁴

Health disparities and their role in the prognosis of pediatric melanoma is another important factor. One study analyzed this relationship at the state level using Texas Cancer Registry data (1995-2009).⁵ Patients’ socioeconomic status (SES) and driving distance to the nearest pediatric cancer care center were included in the analysis. Hispanic children were found to be 3 times more likely to present with advanced disease than non-Hispanic White children. Although SES and distance to the nearest treatment center were not found to affect the melanoma stage at presentation, Hispanic ethnicity or being in the lowest SES quartile were correlated with a higher mortality risk.⁵

When considering specific subtypes of melanoma, acral lentiginous melanoma (ALM) is known to develop in patients with skin of color. A 2023 study by Holman et al⁶ reported that the percentage of melanomas that were ALMs ranged from 0.8% in non-Hispanic White individuals to 19.1% in Hispanic Black, American Indian/Alaska Native, and Asian/Pacific Islander individuals. However, ALM is rare in children. In a pooled cohort study with patient information retrieved from the nationwide Dutch Pathology Registry, only 1 child and 1 adolescent were found to have ALM across a total of 514 patients.⁷ We sought to analyze pediatric melanoma outcomes based on race and other barriers to appropriate care.

We conducted a search of the Surveillance, Epidemiology, and End Results (SEER) database from January 1995 to December 2016 for patients aged 21 years and younger with a primary melanoma diagnosis. The primary outcome was the 5-year survival rate. County-level SES variables were used to calculate a prosperity index. Kaplan-Meier analysis and Cox proportional hazards model were used to compare 5-year survival rates among the different racial/ethnic groups.

A sample of 2742 patients was identified during the study period and followed for 5 years. Eighty-two percent were White, 6% Hispanic, 2% Asian, 1% Black, and 5% classified as other/unknown race (data were missing for 4%). The cohort was predominantly female (61%). White patients were more likely to present with localized disease than any other race/ethnicity (83% vs 65% in Hispanic, 60% in Asian/Pacific Islander, and 45% in Black patients [P<.05]).

Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis. On multivariate analysis, this finding remained significant for Hispanic patients when compared with White patients (hazard ratio, 2.37 [P<.05]). Increasing age, male sex, advanced stage at diagnosis, and failure to receive surgery were associated with increased odds of mortality.

Patients with regionalized and disseminated disease had increased odds of mortality (6.16 and 64.45, respectively; P<.05) compared with patients with localized disease. Socioeconomic status and urbanization were not found to influence 5-year survival rates.

Pediatric melanoma often presents a clinical challenge with special considerations. Pediatric-specific predisposing risk factors for melanoma and an atypical clinical presentation are some of the major concerns that necessitate a tailored approach to this malignancy, especially among different age groups, skin types, and racial and socioeconomic groups.⁵ 

Standard ABCDE criteria often are inadequate for accurate detection of pediatric melanomas. Initial lesions often manifest as raised, red, amelanotic lesions mimicking pyogenic granulomas. Lesions tend to be very small (<6 mm in diameter) and can be uniform in color, thereby making the melanoma more difficult to detect compared to the characteristic findings in adults.⁵ Bleeding or ulceration often can be a warning sign during physical examination.

With regard to incidence, pediatric melanoma is relatively rare. Since the 1970s, the incidence of pediatric melanoma has been increasing; however, a recent analysis of the SEER database showed a decreasing trend from 2000 to 2010.⁴

Our analysis of the SEER data showed an increased risk for pediatric melanoma in older adolescents. In addition, the incidence of pediatric melanoma was higher in females of all racial groups except Asian/Pacific Islander individuals. However, SES was not found to significantly influence the 5-year survival rate in pediatric melanoma.

White pediatric patients were more likely to present with localized disease compared with other races. Pediatric melanoma patients with regional disease had a 6-fold increase in mortality rate vs those with localized disease; those with disseminated disease had a 65-fold higher risk. Consistent with this, Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis.

These findings suggest a relationship between race, melanoma spread, and disease severity. Patient education programs need to be directed specifically to minority groups to improve their knowledge on evolving skin lesions and sun protection practices. Physicians also need to have heightened suspicion and better knowledge of the unique traits of pediatric melanoma.⁵ 

Given the considerable influence these disparities can have on melanoma outcomes, further research is needed to characterize outcomes based on race and determine obstacles to appropriate care. Improved public outreach initiatives that accommodate specific cultural barriers (eg, language, traditional patterns of behavior) also are required to improve current circumstances.

To the Editor:

Skin cancers are extremely common worldwide. Malignant melanomas comprise approximately 1 in 5 of these cancers. Exposure to UV radiation is postulated to be responsible for a global rise in melanoma cases over the past 50 years.¹ Pediatric melanoma is a particularly rare condition that affects approximately 6 in every 1 million children.² Melanoma incidence in children ranges by age, increasing by approximately 10-fold from age 1 to 4 years to age 15 to 19 years. Tumor ulceration is a feature more commonly seen among children younger than 10 years and is associated with worse outcomes. Tumor thickness and ulceration strongly predict sentinel lymph node metastases among children, which also is associated with a poor prognosis.³

A recent study evaluating stage IV melanoma survival rates in adolescents and young adults (AYAs) vs older adults found that survival is much worse among AYAs. Thicker tumors and public health insurance also were associated with worse survival rates for AYAs, while early detection was associated with better survival rates.⁴

Health disparities and their role in the prognosis of pediatric melanoma is another important factor. One study analyzed this relationship at the state level using Texas Cancer Registry data (1995-2009).⁵ Patients’ socioeconomic status (SES) and driving distance to the nearest pediatric cancer care center were included in the analysis. Hispanic children were found to be 3 times more likely to present with advanced disease than non-Hispanic White children. Although SES and distance to the nearest treatment center were not found to affect the melanoma stage at presentation, Hispanic ethnicity or being in the lowest SES quartile were correlated with a higher mortality risk.⁵

When considering specific subtypes of melanoma, acral lentiginous melanoma (ALM) is known to develop in patients with skin of color. A 2023 study by Holman et al⁶ reported that the percentage of melanomas that were ALMs ranged from 0.8% in non-Hispanic White individuals to 19.1% in Hispanic Black, American Indian/Alaska Native, and Asian/Pacific Islander individuals. However, ALM is rare in children. In a pooled cohort study with patient information retrieved from the nationwide Dutch Pathology Registry, only 1 child and 1 adolescent were found to have ALM across a total of 514 patients.⁷ We sought to analyze pediatric melanoma outcomes based on race and other barriers to appropriate care.

We conducted a search of the Surveillance, Epidemiology, and End Results (SEER) database from January 1995 to December 2016 for patients aged 21 years and younger with a primary melanoma diagnosis. The primary outcome was the 5-year survival rate. County-level SES variables were used to calculate a prosperity index. Kaplan-Meier analysis and Cox proportional hazards model were used to compare 5-year survival rates among the different racial/ethnic groups.

A sample of 2742 patients was identified during the study period and followed for 5 years. Eighty-two percent were White, 6% Hispanic, 2% Asian, 1% Black, and 5% classified as other/unknown race (data were missing for 4%). The cohort was predominantly female (61%). White patients were more likely to present with localized disease than any other race/ethnicity (83% vs 65% in Hispanic, 60% in Asian/Pacific Islander, and 45% in Black patients [P<.05]).

Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis. On multivariate analysis, this finding remained significant for Hispanic patients when compared with White patients (hazard ratio, 2.37 [P<.05]). Increasing age, male sex, advanced stage at diagnosis, and failure to receive surgery were associated with increased odds of mortality.

Patients with regionalized and disseminated disease had increased odds of mortality (6.16 and 64.45, respectively; P<.05) compared with patients with localized disease. Socioeconomic status and urbanization were not found to influence 5-year survival rates.

Pediatric melanoma often presents a clinical challenge with special considerations. Pediatric-specific predisposing risk factors for melanoma and an atypical clinical presentation are some of the major concerns that necessitate a tailored approach to this malignancy, especially among different age groups, skin types, and racial and socioeconomic groups.⁵ 

Standard ABCDE criteria often are inadequate for accurate detection of pediatric melanomas. Initial lesions often manifest as raised, red, amelanotic lesions mimicking pyogenic granulomas. Lesions tend to be very small (<6 mm in diameter) and can be uniform in color, thereby making the melanoma more difficult to detect compared to the characteristic findings in adults.⁵ Bleeding or ulceration often can be a warning sign during physical examination.

With regard to incidence, pediatric melanoma is relatively rare. Since the 1970s, the incidence of pediatric melanoma has been increasing; however, a recent analysis of the SEER database showed a decreasing trend from 2000 to 2010.⁴

Our analysis of the SEER data showed an increased risk for pediatric melanoma in older adolescents. In addition, the incidence of pediatric melanoma was higher in females of all racial groups except Asian/Pacific Islander individuals. However, SES was not found to significantly influence the 5-year survival rate in pediatric melanoma.

White pediatric patients were more likely to present with localized disease compared with other races. Pediatric melanoma patients with regional disease had a 6-fold increase in mortality rate vs those with localized disease; those with disseminated disease had a 65-fold higher risk. Consistent with this, Black and Hispanic patients had the worst 5-year survival rates on bivariate analysis.

These findings suggest a relationship between race, melanoma spread, and disease severity. Patient education programs need to be directed specifically to minority groups to improve their knowledge on evolving skin lesions and sun protection practices. Physicians also need to have heightened suspicion and better knowledge of the unique traits of pediatric melanoma.⁵ 

Given the considerable influence these disparities can have on melanoma outcomes, further research is needed to characterize outcomes based on race and determine obstacles to appropriate care. Improved public outreach initiatives that accommodate specific cultural barriers (eg, language, traditional patterns of behavior) also are required to improve current circumstances.

Eyelid dermatitis is a common dermatologic concern representing a broad group of inflammatory dermatoses and typically presenting as eczematous lesions on the eyelids.¹ One of the most common causes of eyelid dermatitis is thought to be allergic contact dermatitis (ACD), a type IV delayed hypersensitivity reaction caused by exposure to external allergens.² Although ACD can occur anywhere on the body, dermatitis on the face and eyelids is quite common.^1,2 This article aims to explore the clinical manifestation, evaluation, and management of eyelid ACD.

Pathophysiology of Eyelid ACD

Studies have shown that ACD is the most common cause of eyelid dermatitis, estimated to account for 46% to 72% of cases worldwide.^3-6 Allergic contact dermatitis is a T cell–mediated type IV hypersensitivity reaction to external antigens that manifests as eczematous lesions at the site of contact with the allergen that may spread.⁷ Allergic contact dermatitis is a common condition, and it is estimated that at least 20% of the general worldwide population has a contact allergy.^8,9 Histologically, ACD manifests as spongiotic dermatitis, though this is not unique and also may be seen in atopic dermatitis (AD) and irritant contact dermatitis.² Allergic contact dermatitis is diagnosed via epicutaneous patch testing, and treatment involves allergen avoidance with or without adjuvant topical and/or systemic immunomodulatory treatments.⁷

The eyelids are uniquely prone to the development of ACD given their thinner epidermis and increased susceptibility to irritation. They frequently are exposed to allergens through the direct topical route as well as indirectly via airborne exposure, rinse-down products (eg, shampoos), and substances transferred from an individual’s own hands. The occluded skin folds of the eyelids facilitate increased exposure to trapped allergens.^10,11 Additionally, the skin of the eyelids is thin, flexible, highly vascularized, and lacking in subcutaneous tissue, making this area more susceptible to antigen penetration than other locations on the body.^1,2,10,12,13

Clinical Manifestations

Eyelid ACD is more common in females than males, which is thought to be related to increased use of cosmetics and fragrances.^1,3,12,14-16 Clinical manifestations may resemble eczematous papules and plaques.¹ Eyelid ACD commonly spreads beyond the eyelid margin, which helps to differentiate it from AD and irritant contact dermatitis. Symptoms of ACD on the eyelids typically include pruritus, redness, swelling, tearing, scaling, and pain.² Persistent untreated eyelid dermatitis can lead to eyelash loss, damage to meibomian glands, and hyperpigmentation.^2,17,18

Patterns of Eyelid ACD

Allergic contact dermatitis on the eyelids can occur due to direct application of allergens onto the skin of the eyelids, runoff of products from the hair/scalp (eg, shampoo), transfer of allergens from the hands, or contact with airborne allergens.^1,2,11,12 Some reports have suggested that eyelid ACD more often is caused by products applied to the scalp or face rather than those applied directly to the eyelids.¹¹ Because the scalp and face are less reactive to contact allergens, in some cases the eyelids may be the only affected site.^10,12,13

The specific pattern of dermatitis on or around the eyelids can provide clues to the allergenic source. Dermatitis present around the eyelids and periorbital region with involvement of the bilateral upper and lower eyelids suggests direct exposure to a contact allergen, such as makeup or other cosmetic products.¹ Unilateral involvement of only 1 eyelid can occur with ectopic transfer of allergens from the hands or nails.^1,19 Involvement of the fingers or nails in addition to the eyelids may further suggest ectopic transfer, such as from allergens in nail polish.¹⁰ Unilateral eyelid dermatitis also could be caused by unique exposures such as a microscope or camera eyepiece.¹⁹ Distribution around the lower eyelids and upper cheeks is indicative of a drip or runoff pattern, which may result from an ophthalmic solution such as eye drops or contact lens solution.^1,19 Finally, dermatitis affecting the upper eyelids along with the nasolabial folds and upper chest may suggest airborne contact dermatitis to fragrances or household cleaning products.^1,11

Common Culprits of Eyelid ACD

Common causes of eyelid ACD include cosmetic products, ophthalmic medications, nail lacquers, and jewelry.^10,13,20 Within the broader category of cosmetics, allergens may be found in makeup and makeup removers, cosmetic applicators and brushes, soaps and cleansers, creams and sunscreens, antiaging products, hair products, nail polish and files, and hair removal products, among many others.^10,13,16,20 Additionally, ophthalmologic and topical medications are common sources of ACD, including eyedrops, contact lens solution, and topical antibiotics.^10,13,21 Costume jewelry commonly contains allergenic metals, which also can be found in eyelash curlers, eyeglasses, toys, and other household items.^22,23 Finally, contact allergens can be found in items such as goggles, gloves, textiles, and a variety of other occupational and household exposures.

Allergic contact dermatitis of the eyelids occurs predominantly—but not exclusively—in females.^16,20,24 This finding has been attributed to the traditionally greater use of cosmetics and fragrances among women; however, the use of skin care products among men is increasing, and recent studies have shown the eyelids to be a common location of facial contact dermatitis among men.^16,24 Although eyelid dermatitis has not been specifically analyzed by sex, a retrospective analysis of 1332 male patients with facial dermatitis found the most common sites to be the face (not otherwise specified)(48.9%), eyelids (23.5%), and lips (12.6%). In this cohort, the most common allergens were surfactants in shampoos and paraphenylenediamine in hair dyes.²⁴

Common Allergens

Common contact allergens among patients with ACD of the eyelids include metals, fragrances, preservatives, acrylates, and topical medications.^{3,10,16,20,25-27} Sources of common contact allergens are reviewed in Table 1.

Metals—Metals are among the most common causes of ACD overall, and nickel frequently is reported as one of the top contact allergens in patients with eyelid dermatitis.^16,27 A retrospective analysis of 2332 patients with eyelid dermatitis patch tested by the North American Contact Dermatitis Group from 1994 to 2016 found that 18.6% of patients with eyelid ACD had a clinically relevant nickel allergy. Sources of nickel exposure include jewelry, grooming devices, makeup and makeup applicators, and eyelash curlers, as well as direct transfer from the hands after contact with consumer products.¹⁶

Other metals that can cause ACD include cobalt (found in similar products to nickel) and gold. Gold often is associated with eyelid dermatitis, though its clinical relevance has been debated, as gold is a relatively inert metal that rarely is present in eye cosmetics and its ions are not displaced from objects and deposited on the skin via sweat in the same way as nickel.^{4,16,20,28-30} Despite this, studies have shown that gold is a common positive patch test reaction among patients with eyelid dermatitis, even in patients with no dermatitis at the site of contact with gold jewelry.^20,29,31 Gold has been reported to be the most common allergen causing unilateral eyelid dermatitis via ectopic transfer.^16,19,20,29 It has been proposed that titanium dioxide, present in many cosmetics and sunscreens, displaces gold allowing its release from jewelry, thereby liberating the fine gold ions and allowing them to desposit on the face and eyelids.^30,31 Given the uncertain clinical relevance of positive patch test reactions to gold, Warshaw at al¹⁶ recommend a 2- to 3-month trial of gold jewelry avoidance to establish relevance, and Ehrlich and Gold²⁹ noted that avoidance of gold leads to improvement.

Fragrances—Fragrances represent a broad category of naturally occurring and man-made components that often are combined to produce a desired scent in personal care products.³² Essential oils and botanicals are both examples of natural fragrances.³³ Fragrances are found in numerous products including makeup, hair products, and household cleaning supplies and represent some of the most common contact allergens.³² Common fragrance allergens include fragrance mixes I and II, hydroperoxides of linalool, and balsam of Peru.^12,32,34 Allergic contact dermatitis to fragrances typically manifests on the eyelids, face, or hands.³³ Several studies have found fragrances to be among the top contact allergens in patients with eyelid dermatitis.^{3,12,20,25,34} Patch testing for fragrance allergy may include baseline series, supplemental fragrance series, and personal care products.^32,35

Preservatives—Preservatives, including formaldehyde and formaldehyde releasers (eg, quaternium-15 and ­bronopol) and methylchloroisothiazolinone/­methylisothiazolinone, may be found in personal care products such as makeup, makeup removers, emollients, shampoos, hair care products, and ophthalmologic solutions and are among the most common cosmetic sources of ACD.^13,36-39 Preservatives are among the top allergens causing eyelid dermatitis.²⁰ In particular, patch test positivity rates to methylchloroisothiazolinone/methylisothiazolinone have been increasing in North America.⁴⁰ Sensitization to preservatives may occur through direct skin contact or transfer from the hands.⁴¹

Acrylates—Acrylates are compounds derived from acrylic acid that may be found in acrylic and gel nails, eyelash extensions, and other adhesives and are frequent causes of eyelid ACD.^4,10,42 Acrylate exposure may be cosmetic among consumers or occupational (eg, aestheticians).^42,43 Acrylates on the nails may cause eyelid dermatitis via ectopic transfer from the hands and also may cause periungual dermatitis manifesting as nail bed erythema.¹⁰ Hydroxyethyl methacrylate is one of the more common eyelid ACD allergens, and studies have shown increasing prevalence of positive reaction rates to hydroxyethylmethacrylate.^10,44Topical Medications—Contact allergies to topical medications are quite common, estimated to occur in 10% to 17% of patients undergoing patch testing.⁴⁵ Both active and inactive ingredients of topical medications may be culprits in eyelid ACD. The most common topical medication allergens include antibiotics, steroids, local anesthetics, and nonsteroidal anti-inflammatory drugs.⁴⁵ Topical antibiotics such as neomycin and bacitracin represent some of the most common causes of eyelid dermatitis^4,10 and may be found in a variety of products, including antibacterial ointments and eye drops.¹ Many ophthalmologic medications also contain corticosteroids, with the most common allergenic steroids being tixocortol pivalate (a marker for hydrocortisone allergy) and budesonide.^10,20 Topical steroids pose a particular dilemma, as they can be either the source of or a treatment for ACD.¹⁰ Eye drops also may contain anesthetics, β-blockers, and antihistamines, as well as the preservative benzalkonium chloride, all of which may be contact allergens.^21,39

Differential Diagnosis of Eyelid Dermatitis

Although ACD is reported to be the most common cause of eyelid dermatitis, the differential diagnosis is broad, including endogenous inflammatory dermatoses and exogenous exposures (Table 2). Symptoms of eyelid ACD can be nonspecific (eg, erythema, pruritus), making diagnosis challenging.⁴⁶

Atopic dermatitis represents another common cause of eyelid dermatitis, accounting for 14% to 39.5% of cases.^3-5,49Atopic dermatitis of the eyelids classically manifests with lichenification of the medial aspects of the eyelids.⁵⁰ Atopic dermatitis and ACD may be difficult to distinguish, as the 2 conditions appear clinically similar and can develop concomitantly.⁵¹ Additionally, atopic patients are likely to have comorbid allergic rhinitis and sensitivity to environmental allergens, which may lead to chronic eye scratching and lichenification.^1,51 Clinical features of eyelid dermatitis suggesting allergic rhinitis and likely comorbid AD include creases in the lower eyelids (Dennie-Morgan lines) and periorbital hyperpigmentation (known as the allergic shiner) due to venous congestion.^1,52

Seborrheic dermatitis is an inflammatory reaction to Malassezia yeast that occurs in sebaceous areas such as the groin, scalp, eyebrows, eyelids, and nasolabial folds.^1,53,54

Irritant contact dermatitis, a nonspecific inflammatory reaction caused by direct cell damage from external irritants, also may affect the eyelids and appear similar to ACD.¹ It typically manifests with a burning or stinging sensation, as opposed to pruritus, and generally develops and resolves more rapidly than ACD.¹ Personal care products are common causes of eyelid irritant contact dermatitis.¹⁶

Patch Testing for Eyelid ACD

The gold standard for diagnosis of ACD is patch testing, outlined by the International Contact Dermatitis Research Group.^55-57 Patch testing generally is performed with standardized panels of allergens and can be customized either with supplemental panels based on unique exposures or with the patient’s own personal care products to increase the sensitivity of testing. Therefore, a thorough history is crucial to identifying potential allergens in a patient’s environment.

False negatives are possible, as the skin on the back may be thicker and less sensitive than the skin at the location of dermatitis.^2,58 This is particularly relevant when using patch testing to diagnose ACD of the eyelids, where the skin is particularly thin and sensitive.² Additionally, ingredients of ophthalmic medications are known to have an especially high false-negative rate with standard patch testing and may require repeated testing with higher drug concentrations or modified patch testing procedures (eg, open testing, scratch-patch testing).^1,59

Treatment

Management of ACD involves allergen avoidance, typically dictated by patch test results.¹⁰ Allergen avoidance may be facilitated using online resources such as the Contact Allergen Management Program (https://www.acdscamp.org/) created by the American Contact Dermatitis Society.^10,18 Patient counseling following patch testing is crucial to educating patients about sources of potential allergen exposures and strategies for avoidance. In the case of eyelid dermatitis, it is particularly important to consider exposure to airborne allergens such as fragrances.¹⁶ Fragrance avoidance is uniquely difficult, as labelling standards in the United States currently do not require disclosure of specific fragrance components.³³ Additionally, products labelled as unscented may still contain fragrances. As such, some patients with fragrance allergy may need to carefully avoid all products containing fragrances.³³

In addition to allergen avoidance, eyelid ACD may be treated with topical medications (eg, steroids, calcineurin inhibitors, Janus kinase inhibitors); however, these same topical medications also can cause ACD due to some ingredients such as propylene glycol.¹⁰ Topical steroids should be used with caution on the eyelids given the risk for atrophy, cataracts, and glaucoma.¹

Final Interpretation

Eyelid dermatitis is a common dermatologic condition most frequently caused by ACD due to exposure to allergens in cosmetic products, ophthalmic medications, nail lacquers, and jewelry, among many other potential sources. The most common allergens causing eyelid dermatitis include metals (particularly nickel), fragrances, preservatives, acrylates, and topical medications. Eyelid ACD is diagnosed via patch testing, and the mainstay of treatment is strict allergen avoidance. Patient counseling is vital for successful allergen avoidance and resolution of eyelid ACD.

Eyelid dermatitis is a common dermatologic concern representing a broad group of inflammatory dermatoses and typically presenting as eczematous lesions on the eyelids.¹ One of the most common causes of eyelid dermatitis is thought to be allergic contact dermatitis (ACD), a type IV delayed hypersensitivity reaction caused by exposure to external allergens.² Although ACD can occur anywhere on the body, dermatitis on the face and eyelids is quite common.^1,2 This article aims to explore the clinical manifestation, evaluation, and management of eyelid ACD.

Pathophysiology of Eyelid ACD

Studies have shown that ACD is the most common cause of eyelid dermatitis, estimated to account for 46% to 72% of cases worldwide.^3-6 Allergic contact dermatitis is a T cell–mediated type IV hypersensitivity reaction to external antigens that manifests as eczematous lesions at the site of contact with the allergen that may spread.⁷ Allergic contact dermatitis is a common condition, and it is estimated that at least 20% of the general worldwide population has a contact allergy.^8,9 Histologically, ACD manifests as spongiotic dermatitis, though this is not unique and also may be seen in atopic dermatitis (AD) and irritant contact dermatitis.² Allergic contact dermatitis is diagnosed via epicutaneous patch testing, and treatment involves allergen avoidance with or without adjuvant topical and/or systemic immunomodulatory treatments.⁷

The eyelids are uniquely prone to the development of ACD given their thinner epidermis and increased susceptibility to irritation. They frequently are exposed to allergens through the direct topical route as well as indirectly via airborne exposure, rinse-down products (eg, shampoos), and substances transferred from an individual’s own hands. The occluded skin folds of the eyelids facilitate increased exposure to trapped allergens.^10,11 Additionally, the skin of the eyelids is thin, flexible, highly vascularized, and lacking in subcutaneous tissue, making this area more susceptible to antigen penetration than other locations on the body.^1,2,10,12,13

Clinical Manifestations

Eyelid ACD is more common in females than males, which is thought to be related to increased use of cosmetics and fragrances.^1,3,12,14-16 Clinical manifestations may resemble eczematous papules and plaques.¹ Eyelid ACD commonly spreads beyond the eyelid margin, which helps to differentiate it from AD and irritant contact dermatitis. Symptoms of ACD on the eyelids typically include pruritus, redness, swelling, tearing, scaling, and pain.² Persistent untreated eyelid dermatitis can lead to eyelash loss, damage to meibomian glands, and hyperpigmentation.^2,17,18

Patterns of Eyelid ACD

Allergic contact dermatitis on the eyelids can occur due to direct application of allergens onto the skin of the eyelids, runoff of products from the hair/scalp (eg, shampoo), transfer of allergens from the hands, or contact with airborne allergens.^1,2,11,12 Some reports have suggested that eyelid ACD more often is caused by products applied to the scalp or face rather than those applied directly to the eyelids.¹¹ Because the scalp and face are less reactive to contact allergens, in some cases the eyelids may be the only affected site.^10,12,13

The specific pattern of dermatitis on or around the eyelids can provide clues to the allergenic source. Dermatitis present around the eyelids and periorbital region with involvement of the bilateral upper and lower eyelids suggests direct exposure to a contact allergen, such as makeup or other cosmetic products.¹ Unilateral involvement of only 1 eyelid can occur with ectopic transfer of allergens from the hands or nails.^1,19 Involvement of the fingers or nails in addition to the eyelids may further suggest ectopic transfer, such as from allergens in nail polish.¹⁰ Unilateral eyelid dermatitis also could be caused by unique exposures such as a microscope or camera eyepiece.¹⁹ Distribution around the lower eyelids and upper cheeks is indicative of a drip or runoff pattern, which may result from an ophthalmic solution such as eye drops or contact lens solution.^1,19 Finally, dermatitis affecting the upper eyelids along with the nasolabial folds and upper chest may suggest airborne contact dermatitis to fragrances or household cleaning products.^1,11

Common Culprits of Eyelid ACD

Common causes of eyelid ACD include cosmetic products, ophthalmic medications, nail lacquers, and jewelry.^10,13,20 Within the broader category of cosmetics, allergens may be found in makeup and makeup removers, cosmetic applicators and brushes, soaps and cleansers, creams and sunscreens, antiaging products, hair products, nail polish and files, and hair removal products, among many others.^10,13,16,20 Additionally, ophthalmologic and topical medications are common sources of ACD, including eyedrops, contact lens solution, and topical antibiotics.^10,13,21 Costume jewelry commonly contains allergenic metals, which also can be found in eyelash curlers, eyeglasses, toys, and other household items.^22,23 Finally, contact allergens can be found in items such as goggles, gloves, textiles, and a variety of other occupational and household exposures.

Allergic contact dermatitis of the eyelids occurs predominantly—but not exclusively—in females.^16,20,24 This finding has been attributed to the traditionally greater use of cosmetics and fragrances among women; however, the use of skin care products among men is increasing, and recent studies have shown the eyelids to be a common location of facial contact dermatitis among men.^16,24 Although eyelid dermatitis has not been specifically analyzed by sex, a retrospective analysis of 1332 male patients with facial dermatitis found the most common sites to be the face (not otherwise specified)(48.9%), eyelids (23.5%), and lips (12.6%). In this cohort, the most common allergens were surfactants in shampoos and paraphenylenediamine in hair dyes.²⁴

Common Allergens

Common contact allergens among patients with ACD of the eyelids include metals, fragrances, preservatives, acrylates, and topical medications.^{3,10,16,20,25-27} Sources of common contact allergens are reviewed in Table 1.

Metals—Metals are among the most common causes of ACD overall, and nickel frequently is reported as one of the top contact allergens in patients with eyelid dermatitis.^16,27 A retrospective analysis of 2332 patients with eyelid dermatitis patch tested by the North American Contact Dermatitis Group from 1994 to 2016 found that 18.6% of patients with eyelid ACD had a clinically relevant nickel allergy. Sources of nickel exposure include jewelry, grooming devices, makeup and makeup applicators, and eyelash curlers, as well as direct transfer from the hands after contact with consumer products.¹⁶

Other metals that can cause ACD include cobalt (found in similar products to nickel) and gold. Gold often is associated with eyelid dermatitis, though its clinical relevance has been debated, as gold is a relatively inert metal that rarely is present in eye cosmetics and its ions are not displaced from objects and deposited on the skin via sweat in the same way as nickel.^{4,16,20,28-30} Despite this, studies have shown that gold is a common positive patch test reaction among patients with eyelid dermatitis, even in patients with no dermatitis at the site of contact with gold jewelry.^20,29,31 Gold has been reported to be the most common allergen causing unilateral eyelid dermatitis via ectopic transfer.^16,19,20,29 It has been proposed that titanium dioxide, present in many cosmetics and sunscreens, displaces gold allowing its release from jewelry, thereby liberating the fine gold ions and allowing them to desposit on the face and eyelids.^30,31 Given the uncertain clinical relevance of positive patch test reactions to gold, Warshaw at al¹⁶ recommend a 2- to 3-month trial of gold jewelry avoidance to establish relevance, and Ehrlich and Gold²⁹ noted that avoidance of gold leads to improvement.

Fragrances—Fragrances represent a broad category of naturally occurring and man-made components that often are combined to produce a desired scent in personal care products.³² Essential oils and botanicals are both examples of natural fragrances.³³ Fragrances are found in numerous products including makeup, hair products, and household cleaning supplies and represent some of the most common contact allergens.³² Common fragrance allergens include fragrance mixes I and II, hydroperoxides of linalool, and balsam of Peru.^12,32,34 Allergic contact dermatitis to fragrances typically manifests on the eyelids, face, or hands.³³ Several studies have found fragrances to be among the top contact allergens in patients with eyelid dermatitis.^{3,12,20,25,34} Patch testing for fragrance allergy may include baseline series, supplemental fragrance series, and personal care products.^32,35

Preservatives—Preservatives, including formaldehyde and formaldehyde releasers (eg, quaternium-15 and ­bronopol) and methylchloroisothiazolinone/­methylisothiazolinone, may be found in personal care products such as makeup, makeup removers, emollients, shampoos, hair care products, and ophthalmologic solutions and are among the most common cosmetic sources of ACD.^13,36-39 Preservatives are among the top allergens causing eyelid dermatitis.²⁰ In particular, patch test positivity rates to methylchloroisothiazolinone/methylisothiazolinone have been increasing in North America.⁴⁰ Sensitization to preservatives may occur through direct skin contact or transfer from the hands.⁴¹

Acrylates—Acrylates are compounds derived from acrylic acid that may be found in acrylic and gel nails, eyelash extensions, and other adhesives and are frequent causes of eyelid ACD.^4,10,42 Acrylate exposure may be cosmetic among consumers or occupational (eg, aestheticians).^42,43 Acrylates on the nails may cause eyelid dermatitis via ectopic transfer from the hands and also may cause periungual dermatitis manifesting as nail bed erythema.¹⁰ Hydroxyethyl methacrylate is one of the more common eyelid ACD allergens, and studies have shown increasing prevalence of positive reaction rates to hydroxyethylmethacrylate.^10,44Topical Medications—Contact allergies to topical medications are quite common, estimated to occur in 10% to 17% of patients undergoing patch testing.⁴⁵ Both active and inactive ingredients of topical medications may be culprits in eyelid ACD. The most common topical medication allergens include antibiotics, steroids, local anesthetics, and nonsteroidal anti-inflammatory drugs.⁴⁵ Topical antibiotics such as neomycin and bacitracin represent some of the most common causes of eyelid dermatitis^4,10 and may be found in a variety of products, including antibacterial ointments and eye drops.¹ Many ophthalmologic medications also contain corticosteroids, with the most common allergenic steroids being tixocortol pivalate (a marker for hydrocortisone allergy) and budesonide.^10,20 Topical steroids pose a particular dilemma, as they can be either the source of or a treatment for ACD.¹⁰ Eye drops also may contain anesthetics, β-blockers, and antihistamines, as well as the preservative benzalkonium chloride, all of which may be contact allergens.^21,39

Differential Diagnosis of Eyelid Dermatitis

Although ACD is reported to be the most common cause of eyelid dermatitis, the differential diagnosis is broad, including endogenous inflammatory dermatoses and exogenous exposures (Table 2). Symptoms of eyelid ACD can be nonspecific (eg, erythema, pruritus), making diagnosis challenging.⁴⁶

Atopic dermatitis represents another common cause of eyelid dermatitis, accounting for 14% to 39.5% of cases.^3-5,49Atopic dermatitis of the eyelids classically manifests with lichenification of the medial aspects of the eyelids.⁵⁰ Atopic dermatitis and ACD may be difficult to distinguish, as the 2 conditions appear clinically similar and can develop concomitantly.⁵¹ Additionally, atopic patients are likely to have comorbid allergic rhinitis and sensitivity to environmental allergens, which may lead to chronic eye scratching and lichenification.^1,51 Clinical features of eyelid dermatitis suggesting allergic rhinitis and likely comorbid AD include creases in the lower eyelids (Dennie-Morgan lines) and periorbital hyperpigmentation (known as the allergic shiner) due to venous congestion.^1,52

Seborrheic dermatitis is an inflammatory reaction to Malassezia yeast that occurs in sebaceous areas such as the groin, scalp, eyebrows, eyelids, and nasolabial folds.^1,53,54

Irritant contact dermatitis, a nonspecific inflammatory reaction caused by direct cell damage from external irritants, also may affect the eyelids and appear similar to ACD.¹ It typically manifests with a burning or stinging sensation, as opposed to pruritus, and generally develops and resolves more rapidly than ACD.¹ Personal care products are common causes of eyelid irritant contact dermatitis.¹⁶

Patch Testing for Eyelid ACD

The gold standard for diagnosis of ACD is patch testing, outlined by the International Contact Dermatitis Research Group.^55-57 Patch testing generally is performed with standardized panels of allergens and can be customized either with supplemental panels based on unique exposures or with the patient’s own personal care products to increase the sensitivity of testing. Therefore, a thorough history is crucial to identifying potential allergens in a patient’s environment.

False negatives are possible, as the skin on the back may be thicker and less sensitive than the skin at the location of dermatitis.^2,58 This is particularly relevant when using patch testing to diagnose ACD of the eyelids, where the skin is particularly thin and sensitive.² Additionally, ingredients of ophthalmic medications are known to have an especially high false-negative rate with standard patch testing and may require repeated testing with higher drug concentrations or modified patch testing procedures (eg, open testing, scratch-patch testing).^1,59

Treatment

Management of ACD involves allergen avoidance, typically dictated by patch test results.¹⁰ Allergen avoidance may be facilitated using online resources such as the Contact Allergen Management Program (https://www.acdscamp.org/) created by the American Contact Dermatitis Society.^10,18 Patient counseling following patch testing is crucial to educating patients about sources of potential allergen exposures and strategies for avoidance. In the case of eyelid dermatitis, it is particularly important to consider exposure to airborne allergens such as fragrances.¹⁶ Fragrance avoidance is uniquely difficult, as labelling standards in the United States currently do not require disclosure of specific fragrance components.³³ Additionally, products labelled as unscented may still contain fragrances. As such, some patients with fragrance allergy may need to carefully avoid all products containing fragrances.³³

In addition to allergen avoidance, eyelid ACD may be treated with topical medications (eg, steroids, calcineurin inhibitors, Janus kinase inhibitors); however, these same topical medications also can cause ACD due to some ingredients such as propylene glycol.¹⁰ Topical steroids should be used with caution on the eyelids given the risk for atrophy, cataracts, and glaucoma.¹

Final Interpretation

Eyelid dermatitis is a common dermatologic condition most frequently caused by ACD due to exposure to allergens in cosmetic products, ophthalmic medications, nail lacquers, and jewelry, among many other potential sources. The most common allergens causing eyelid dermatitis include metals (particularly nickel), fragrances, preservatives, acrylates, and topical medications. Eyelid ACD is diagnosed via patch testing, and the mainstay of treatment is strict allergen avoidance. Patient counseling is vital for successful allergen avoidance and resolution of eyelid ACD.

Eyelid dermatitis is a common dermatologic concern representing a broad group of inflammatory dermatoses and typically presenting as eczematous lesions on the eyelids.¹ One of the most common causes of eyelid dermatitis is thought to be allergic contact dermatitis (ACD), a type IV delayed hypersensitivity reaction caused by exposure to external allergens.² Although ACD can occur anywhere on the body, dermatitis on the face and eyelids is quite common.^1,2 This article aims to explore the clinical manifestation, evaluation, and management of eyelid ACD.

Pathophysiology of Eyelid ACD

Studies have shown that ACD is the most common cause of eyelid dermatitis, estimated to account for 46% to 72% of cases worldwide.^3-6 Allergic contact dermatitis is a T cell–mediated type IV hypersensitivity reaction to external antigens that manifests as eczematous lesions at the site of contact with the allergen that may spread.⁷ Allergic contact dermatitis is a common condition, and it is estimated that at least 20% of the general worldwide population has a contact allergy.^8,9 Histologically, ACD manifests as spongiotic dermatitis, though this is not unique and also may be seen in atopic dermatitis (AD) and irritant contact dermatitis.² Allergic contact dermatitis is diagnosed via epicutaneous patch testing, and treatment involves allergen avoidance with or without adjuvant topical and/or systemic immunomodulatory treatments.⁷

The eyelids are uniquely prone to the development of ACD given their thinner epidermis and increased susceptibility to irritation. They frequently are exposed to allergens through the direct topical route as well as indirectly via airborne exposure, rinse-down products (eg, shampoos), and substances transferred from an individual’s own hands. The occluded skin folds of the eyelids facilitate increased exposure to trapped allergens.^10,11 Additionally, the skin of the eyelids is thin, flexible, highly vascularized, and lacking in subcutaneous tissue, making this area more susceptible to antigen penetration than other locations on the body.^1,2,10,12,13

Clinical Manifestations

Eyelid ACD is more common in females than males, which is thought to be related to increased use of cosmetics and fragrances.^1,3,12,14-16 Clinical manifestations may resemble eczematous papules and plaques.¹ Eyelid ACD commonly spreads beyond the eyelid margin, which helps to differentiate it from AD and irritant contact dermatitis. Symptoms of ACD on the eyelids typically include pruritus, redness, swelling, tearing, scaling, and pain.² Persistent untreated eyelid dermatitis can lead to eyelash loss, damage to meibomian glands, and hyperpigmentation.^2,17,18

Patterns of Eyelid ACD

Allergic contact dermatitis on the eyelids can occur due to direct application of allergens onto the skin of the eyelids, runoff of products from the hair/scalp (eg, shampoo), transfer of allergens from the hands, or contact with airborne allergens.^1,2,11,12 Some reports have suggested that eyelid ACD more often is caused by products applied to the scalp or face rather than those applied directly to the eyelids.¹¹ Because the scalp and face are less reactive to contact allergens, in some cases the eyelids may be the only affected site.^10,12,13

The specific pattern of dermatitis on or around the eyelids can provide clues to the allergenic source. Dermatitis present around the eyelids and periorbital region with involvement of the bilateral upper and lower eyelids suggests direct exposure to a contact allergen, such as makeup or other cosmetic products.¹ Unilateral involvement of only 1 eyelid can occur with ectopic transfer of allergens from the hands or nails.^1,19 Involvement of the fingers or nails in addition to the eyelids may further suggest ectopic transfer, such as from allergens in nail polish.¹⁰ Unilateral eyelid dermatitis also could be caused by unique exposures such as a microscope or camera eyepiece.¹⁹ Distribution around the lower eyelids and upper cheeks is indicative of a drip or runoff pattern, which may result from an ophthalmic solution such as eye drops or contact lens solution.^1,19 Finally, dermatitis affecting the upper eyelids along with the nasolabial folds and upper chest may suggest airborne contact dermatitis to fragrances or household cleaning products.^1,11

Common Culprits of Eyelid ACD

Common causes of eyelid ACD include cosmetic products, ophthalmic medications, nail lacquers, and jewelry.^10,13,20 Within the broader category of cosmetics, allergens may be found in makeup and makeup removers, cosmetic applicators and brushes, soaps and cleansers, creams and sunscreens, antiaging products, hair products, nail polish and files, and hair removal products, among many others.^10,13,16,20 Additionally, ophthalmologic and topical medications are common sources of ACD, including eyedrops, contact lens solution, and topical antibiotics.^10,13,21 Costume jewelry commonly contains allergenic metals, which also can be found in eyelash curlers, eyeglasses, toys, and other household items.^22,23 Finally, contact allergens can be found in items such as goggles, gloves, textiles, and a variety of other occupational and household exposures.

Allergic contact dermatitis of the eyelids occurs predominantly—but not exclusively—in females.^16,20,24 This finding has been attributed to the traditionally greater use of cosmetics and fragrances among women; however, the use of skin care products among men is increasing, and recent studies have shown the eyelids to be a common location of facial contact dermatitis among men.^16,24 Although eyelid dermatitis has not been specifically analyzed by sex, a retrospective analysis of 1332 male patients with facial dermatitis found the most common sites to be the face (not otherwise specified)(48.9%), eyelids (23.5%), and lips (12.6%). In this cohort, the most common allergens were surfactants in shampoos and paraphenylenediamine in hair dyes.²⁴

Common Allergens

Common contact allergens among patients with ACD of the eyelids include metals, fragrances, preservatives, acrylates, and topical medications.^{3,10,16,20,25-27} Sources of common contact allergens are reviewed in Table 1.

Metals—Metals are among the most common causes of ACD overall, and nickel frequently is reported as one of the top contact allergens in patients with eyelid dermatitis.^16,27 A retrospective analysis of 2332 patients with eyelid dermatitis patch tested by the North American Contact Dermatitis Group from 1994 to 2016 found that 18.6% of patients with eyelid ACD had a clinically relevant nickel allergy. Sources of nickel exposure include jewelry, grooming devices, makeup and makeup applicators, and eyelash curlers, as well as direct transfer from the hands after contact with consumer products.¹⁶

Other metals that can cause ACD include cobalt (found in similar products to nickel) and gold. Gold often is associated with eyelid dermatitis, though its clinical relevance has been debated, as gold is a relatively inert metal that rarely is present in eye cosmetics and its ions are not displaced from objects and deposited on the skin via sweat in the same way as nickel.^{4,16,20,28-30} Despite this, studies have shown that gold is a common positive patch test reaction among patients with eyelid dermatitis, even in patients with no dermatitis at the site of contact with gold jewelry.^20,29,31 Gold has been reported to be the most common allergen causing unilateral eyelid dermatitis via ectopic transfer.^16,19,20,29 It has been proposed that titanium dioxide, present in many cosmetics and sunscreens, displaces gold allowing its release from jewelry, thereby liberating the fine gold ions and allowing them to desposit on the face and eyelids.^30,31 Given the uncertain clinical relevance of positive patch test reactions to gold, Warshaw at al¹⁶ recommend a 2- to 3-month trial of gold jewelry avoidance to establish relevance, and Ehrlich and Gold²⁹ noted that avoidance of gold leads to improvement.

Fragrances—Fragrances represent a broad category of naturally occurring and man-made components that often are combined to produce a desired scent in personal care products.³² Essential oils and botanicals are both examples of natural fragrances.³³ Fragrances are found in numerous products including makeup, hair products, and household cleaning supplies and represent some of the most common contact allergens.³² Common fragrance allergens include fragrance mixes I and II, hydroperoxides of linalool, and balsam of Peru.^12,32,34 Allergic contact dermatitis to fragrances typically manifests on the eyelids, face, or hands.³³ Several studies have found fragrances to be among the top contact allergens in patients with eyelid dermatitis.^{3,12,20,25,34} Patch testing for fragrance allergy may include baseline series, supplemental fragrance series, and personal care products.^32,35

Preservatives—Preservatives, including formaldehyde and formaldehyde releasers (eg, quaternium-15 and ­bronopol) and methylchloroisothiazolinone/­methylisothiazolinone, may be found in personal care products such as makeup, makeup removers, emollients, shampoos, hair care products, and ophthalmologic solutions and are among the most common cosmetic sources of ACD.^13,36-39 Preservatives are among the top allergens causing eyelid dermatitis.²⁰ In particular, patch test positivity rates to methylchloroisothiazolinone/methylisothiazolinone have been increasing in North America.⁴⁰ Sensitization to preservatives may occur through direct skin contact or transfer from the hands.⁴¹

Acrylates—Acrylates are compounds derived from acrylic acid that may be found in acrylic and gel nails, eyelash extensions, and other adhesives and are frequent causes of eyelid ACD.^4,10,42 Acrylate exposure may be cosmetic among consumers or occupational (eg, aestheticians).^42,43 Acrylates on the nails may cause eyelid dermatitis via ectopic transfer from the hands and also may cause periungual dermatitis manifesting as nail bed erythema.¹⁰ Hydroxyethyl methacrylate is one of the more common eyelid ACD allergens, and studies have shown increasing prevalence of positive reaction rates to hydroxyethylmethacrylate.^10,44Topical Medications—Contact allergies to topical medications are quite common, estimated to occur in 10% to 17% of patients undergoing patch testing.⁴⁵ Both active and inactive ingredients of topical medications may be culprits in eyelid ACD. The most common topical medication allergens include antibiotics, steroids, local anesthetics, and nonsteroidal anti-inflammatory drugs.⁴⁵ Topical antibiotics such as neomycin and bacitracin represent some of the most common causes of eyelid dermatitis^4,10 and may be found in a variety of products, including antibacterial ointments and eye drops.¹ Many ophthalmologic medications also contain corticosteroids, with the most common allergenic steroids being tixocortol pivalate (a marker for hydrocortisone allergy) and budesonide.^10,20 Topical steroids pose a particular dilemma, as they can be either the source of or a treatment for ACD.¹⁰ Eye drops also may contain anesthetics, β-blockers, and antihistamines, as well as the preservative benzalkonium chloride, all of which may be contact allergens.^21,39

Differential Diagnosis of Eyelid Dermatitis

Although ACD is reported to be the most common cause of eyelid dermatitis, the differential diagnosis is broad, including endogenous inflammatory dermatoses and exogenous exposures (Table 2). Symptoms of eyelid ACD can be nonspecific (eg, erythema, pruritus), making diagnosis challenging.⁴⁶

Atopic dermatitis represents another common cause of eyelid dermatitis, accounting for 14% to 39.5% of cases.^3-5,49Atopic dermatitis of the eyelids classically manifests with lichenification of the medial aspects of the eyelids.⁵⁰ Atopic dermatitis and ACD may be difficult to distinguish, as the 2 conditions appear clinically similar and can develop concomitantly.⁵¹ Additionally, atopic patients are likely to have comorbid allergic rhinitis and sensitivity to environmental allergens, which may lead to chronic eye scratching and lichenification.^1,51 Clinical features of eyelid dermatitis suggesting allergic rhinitis and likely comorbid AD include creases in the lower eyelids (Dennie-Morgan lines) and periorbital hyperpigmentation (known as the allergic shiner) due to venous congestion.^1,52

Seborrheic dermatitis is an inflammatory reaction to Malassezia yeast that occurs in sebaceous areas such as the groin, scalp, eyebrows, eyelids, and nasolabial folds.^1,53,54

Irritant contact dermatitis, a nonspecific inflammatory reaction caused by direct cell damage from external irritants, also may affect the eyelids and appear similar to ACD.¹ It typically manifests with a burning or stinging sensation, as opposed to pruritus, and generally develops and resolves more rapidly than ACD.¹ Personal care products are common causes of eyelid irritant contact dermatitis.¹⁶

Patch Testing for Eyelid ACD

The gold standard for diagnosis of ACD is patch testing, outlined by the International Contact Dermatitis Research Group.^55-57 Patch testing generally is performed with standardized panels of allergens and can be customized either with supplemental panels based on unique exposures or with the patient’s own personal care products to increase the sensitivity of testing. Therefore, a thorough history is crucial to identifying potential allergens in a patient’s environment.

False negatives are possible, as the skin on the back may be thicker and less sensitive than the skin at the location of dermatitis.^2,58 This is particularly relevant when using patch testing to diagnose ACD of the eyelids, where the skin is particularly thin and sensitive.² Additionally, ingredients of ophthalmic medications are known to have an especially high false-negative rate with standard patch testing and may require repeated testing with higher drug concentrations or modified patch testing procedures (eg, open testing, scratch-patch testing).^1,59

Treatment

Management of ACD involves allergen avoidance, typically dictated by patch test results.¹⁰ Allergen avoidance may be facilitated using online resources such as the Contact Allergen Management Program (https://www.acdscamp.org/) created by the American Contact Dermatitis Society.^10,18 Patient counseling following patch testing is crucial to educating patients about sources of potential allergen exposures and strategies for avoidance. In the case of eyelid dermatitis, it is particularly important to consider exposure to airborne allergens such as fragrances.¹⁶ Fragrance avoidance is uniquely difficult, as labelling standards in the United States currently do not require disclosure of specific fragrance components.³³ Additionally, products labelled as unscented may still contain fragrances. As such, some patients with fragrance allergy may need to carefully avoid all products containing fragrances.³³

In addition to allergen avoidance, eyelid ACD may be treated with topical medications (eg, steroids, calcineurin inhibitors, Janus kinase inhibitors); however, these same topical medications also can cause ACD due to some ingredients such as propylene glycol.¹⁰ Topical steroids should be used with caution on the eyelids given the risk for atrophy, cataracts, and glaucoma.¹

Final Interpretation

Eyelid dermatitis is a common dermatologic condition most frequently caused by ACD due to exposure to allergens in cosmetic products, ophthalmic medications, nail lacquers, and jewelry, among many other potential sources. The most common allergens causing eyelid dermatitis include metals (particularly nickel), fragrances, preservatives, acrylates, and topical medications. Eyelid ACD is diagnosed via patch testing, and the mainstay of treatment is strict allergen avoidance. Patient counseling is vital for successful allergen avoidance and resolution of eyelid ACD.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

SAN DIEGO — Although it has been known for several years that more than 1000 species of bacteria from 19 different phyla inhabit the human skin — mainly the superficial epidermis and upper parts of the hair follicles — published studies specifically focusing on the skin microbiome remain limited. 

In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. 

“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.” 
 

A Shield From Foreign Pathogens

At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ” 

According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.” 

Daryl Leja, National Human Genome Research Institute

• Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
• Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
• Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
• Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.

Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.” 

According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.” 

Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
 

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

SAN DIEGO — Although it has been known for several years that more than 1000 species of bacteria from 19 different phyla inhabit the human skin — mainly the superficial epidermis and upper parts of the hair follicles — published studies specifically focusing on the skin microbiome remain limited. 

In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. 

“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.” 
 

A Shield From Foreign Pathogens

At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ” 

According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.” 

Daryl Leja, National Human Genome Research Institute

• Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
• Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
• Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
• Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.

Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.” 

According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.” 

Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
 

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

SAN DIEGO — Although it has been known for several years that more than 1000 species of bacteria from 19 different phyla inhabit the human skin — mainly the superficial epidermis and upper parts of the hair follicles — published studies specifically focusing on the skin microbiome remain limited. 

In one review of the topic, researchers from the National Institutes of Health wrote that the skin is composed of 1.8 million diverse habitats with an abundance of folds, invaginations, and specialized niches that support a wide range of microorganisms. “Many of these microorganisms are harmless and, in some cases, provide vital functions for us to live and they have not evolved over time,” Jill S. Waibel, MD, medical director of the Miami Dermatology and Laser Institute, said at the annual Masters of Aesthetics Symposium. 

“This is complex ecosystem that we don’t really talk about,” she said. “There is wide topographical distribution of bacteria on skin sites. The bacteria we have on our head and neck area is different from that on our feet. There is also a lot of interpersonal variation of the skin microbiome, so one person may have a lot of one type of bacteria and not as much of another.” 
 

A Shield From Foreign Pathogens

At its core, Dr. Waibel continued, the skin microbiome functions as an interface between the human body and the environment, a physical barrier that prevents the invasion of foreign pathogens. The skin also provides a home to commensal microbiota. She likened the skin’s landscape to that of the tundra: “It’s desiccated, has poor nutrients, and it’s very acidic, thus pathogens have a hard time living on it,” she said. “However, our skin microorganisms have adapted to utilize the sparse nutrients available on the skin. That’s why I tell my patients, ‘don’t use a sugar scrub because you’re potentially feeding these bad bacteria.’ ” 

According to more recent research, the skin microbiota in healthy adults remains stable over time, despite environmental perturbations, and they have important roles in educating the innate and adaptive arms of the cutaneous immune system. “Some skin diseases are associated with an altered microbial state: dysbiosis,” said Dr. Waibel, subsection chief of dermatology at Baptist Health South Florida, Miami Beach. “Reversion of this may help prevent or treat the disease.” 

Daryl Leja, National Human Genome Research Institute

• Genetics affects the skin microbiome considerably. Individuals with autoimmune predispositions have different microbiota compared with those who don’t.
• Climate, pollution, and hygiene practices the other influencing factors. “Even clothing can impact the microbiome, by causing the transfer of microorganisms,” she said.
• Age and hormonal changes (particularly during puberty) and senescence alter the microbial landscape.
• Systemic health conditions such as diabetes mellitus and irritable bowel disease, as well as cutaneous conditions like psoriasis and atopic dermatitis can also disrupt the skin microbiome.

Ingredients contained in soaps, antibiotics, and cosmetics can also cause skin dysbiosis, Dr. Waibel said. However, the integrity of the skin’s microbiome following dermatological procedures such as excisions, dermabrasion, laser therapy, and other physical procedures is less understood, according to a recent review of the topic. Phototherapy appears to be the most extensively studied, “and shows an increase in microbial diversity post-treatment,” she said. “Light treatments have been found to kill bacteria by inducing DNA damage. More studies need to be performed on specific wavelengths of light used, conditions being treated and individual patient differences.” 

According to the review’s authors, no change in the microbiome was observed in studies of debridement. “That was surprising, as it is a method to remove unhealthy tissue that often contains pathogenic bacteria,” Dr. Waibel said. “The big take-home message is that we need more research.” 

Dr. Waibel disclosed that she has conducted clinical trials for several device and pharmaceutical companies.
 

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