MDedge Dermatology

The Food and Drug Administration issued a warning today about the use of needle-free devices for injecting dermal fillers – which are promoted to the public on social media and have resulted in serious and permanent injuries.

Specifically, the warning advises consumers and health care professionals “not to use needle-free devices such as hyaluron pens for injection of hyaluronic acid (HA) or other lip and facial fillers, collectively and commonly referred to as dermal fillers or fillers.”

According to the statement, the agency “is aware of serious injuries and in some cases, permanent harm to the skin, lips, or eyes with the use of needle-free devices for injection of fillers.”

Needle-free devices and lip and facial fillers for use with these devices are being sold directly to consumers online, and are promoted on social media “to increase lip volume, improve the appearance of wrinkles, change the shape of the nose, and other similar procedures,” according to the FDA warning.

The FDA points out that FDA-approved dermal fillers are for prescription use only, and should be administered only by licensed health care professionals using a syringe with a needle or cannula, and advises consumers not to buy or use lip or facial fillers sold directly to the public.

These products may be contaminated with infectious agents or chemicals. Moreover, “needle-free injection devices for aesthetic purposes do not provide enough control over where the injected product is placed,” the statement adds. In addition to infections, other risks include bleeding and bruising, formation of lumps, allergic reactions, blockage of a blood vessel (which can result in necrosis, blindness, or stroke), and transmission of diseases from sharing devices.

The FDA’s recommendations for health care providers include not using any aesthetic fillers with a needle-free device, and not using approved dermal fillers in such devices.

The American Society for Dermatologic Surgery Association (ASDSA) commended the FDA on the safety communication in a statement issued on October 11. In February, the ASDSA issued an alert about children using hyaluron pens to self-inject hyaluronic filler into the epidermal and upper dermal skin layers. 

“I am pleased that the FDA has taken notice of this disturbing new trend, especially that of children using these devices on social media,” ASDSA president Mathew Avram, MD, JD, director of the Dermatology Laser and Cosmetic Center, at Massachusetts General Hospital, Boston, said in the statement. “The complexity of facial anatomy requires in-depth knowledge and expertise, and patients should always have medical procedures done by a physician who also has knowledge of adverse events,” he added, urging consumers to see a board-certified dermatologist before undergoing any cosmetic procedure.

In response to a query, an FDA spokesperson did not have an estimate of the number of reports of these adverse events.

People who have problems or are concerned about having had a filler injected with a needle-free device should contact a licensed health care provider. Consumers and health care professionals should report adverse events related to injection of fillers with a needle-free device to the FDA’s MedWatch program. In addition to MedWatch, adverse events can also be reported to the Cutaneous Procedures Adverse Events Reporting (CAPER) Registry, established earlier this year by the ASDSA with the department of dermatology at Northwestern University, Chicago.

*This story was updated on October 12. 

The Food and Drug Administration issued a warning today about the use of needle-free devices for injecting dermal fillers – which are promoted to the public on social media and have resulted in serious and permanent injuries.

Specifically, the warning advises consumers and health care professionals “not to use needle-free devices such as hyaluron pens for injection of hyaluronic acid (HA) or other lip and facial fillers, collectively and commonly referred to as dermal fillers or fillers.”

According to the statement, the agency “is aware of serious injuries and in some cases, permanent harm to the skin, lips, or eyes with the use of needle-free devices for injection of fillers.”

Needle-free devices and lip and facial fillers for use with these devices are being sold directly to consumers online, and are promoted on social media “to increase lip volume, improve the appearance of wrinkles, change the shape of the nose, and other similar procedures,” according to the FDA warning.

The FDA points out that FDA-approved dermal fillers are for prescription use only, and should be administered only by licensed health care professionals using a syringe with a needle or cannula, and advises consumers not to buy or use lip or facial fillers sold directly to the public.

These products may be contaminated with infectious agents or chemicals. Moreover, “needle-free injection devices for aesthetic purposes do not provide enough control over where the injected product is placed,” the statement adds. In addition to infections, other risks include bleeding and bruising, formation of lumps, allergic reactions, blockage of a blood vessel (which can result in necrosis, blindness, or stroke), and transmission of diseases from sharing devices.

The FDA’s recommendations for health care providers include not using any aesthetic fillers with a needle-free device, and not using approved dermal fillers in such devices.

The American Society for Dermatologic Surgery Association (ASDSA) commended the FDA on the safety communication in a statement issued on October 11. In February, the ASDSA issued an alert about children using hyaluron pens to self-inject hyaluronic filler into the epidermal and upper dermal skin layers. 

“I am pleased that the FDA has taken notice of this disturbing new trend, especially that of children using these devices on social media,” ASDSA president Mathew Avram, MD, JD, director of the Dermatology Laser and Cosmetic Center, at Massachusetts General Hospital, Boston, said in the statement. “The complexity of facial anatomy requires in-depth knowledge and expertise, and patients should always have medical procedures done by a physician who also has knowledge of adverse events,” he added, urging consumers to see a board-certified dermatologist before undergoing any cosmetic procedure.

In response to a query, an FDA spokesperson did not have an estimate of the number of reports of these adverse events.

People who have problems or are concerned about having had a filler injected with a needle-free device should contact a licensed health care provider. Consumers and health care professionals should report adverse events related to injection of fillers with a needle-free device to the FDA’s MedWatch program. In addition to MedWatch, adverse events can also be reported to the Cutaneous Procedures Adverse Events Reporting (CAPER) Registry, established earlier this year by the ASDSA with the department of dermatology at Northwestern University, Chicago.

*This story was updated on October 12. 

The Food and Drug Administration issued a warning today about the use of needle-free devices for injecting dermal fillers – which are promoted to the public on social media and have resulted in serious and permanent injuries.

Specifically, the warning advises consumers and health care professionals “not to use needle-free devices such as hyaluron pens for injection of hyaluronic acid (HA) or other lip and facial fillers, collectively and commonly referred to as dermal fillers or fillers.”

According to the statement, the agency “is aware of serious injuries and in some cases, permanent harm to the skin, lips, or eyes with the use of needle-free devices for injection of fillers.”

Needle-free devices and lip and facial fillers for use with these devices are being sold directly to consumers online, and are promoted on social media “to increase lip volume, improve the appearance of wrinkles, change the shape of the nose, and other similar procedures,” according to the FDA warning.

The FDA points out that FDA-approved dermal fillers are for prescription use only, and should be administered only by licensed health care professionals using a syringe with a needle or cannula, and advises consumers not to buy or use lip or facial fillers sold directly to the public.

These products may be contaminated with infectious agents or chemicals. Moreover, “needle-free injection devices for aesthetic purposes do not provide enough control over where the injected product is placed,” the statement adds. In addition to infections, other risks include bleeding and bruising, formation of lumps, allergic reactions, blockage of a blood vessel (which can result in necrosis, blindness, or stroke), and transmission of diseases from sharing devices.

The FDA’s recommendations for health care providers include not using any aesthetic fillers with a needle-free device, and not using approved dermal fillers in such devices.

The American Society for Dermatologic Surgery Association (ASDSA) commended the FDA on the safety communication in a statement issued on October 11. In February, the ASDSA issued an alert about children using hyaluron pens to self-inject hyaluronic filler into the epidermal and upper dermal skin layers. 

“I am pleased that the FDA has taken notice of this disturbing new trend, especially that of children using these devices on social media,” ASDSA president Mathew Avram, MD, JD, director of the Dermatology Laser and Cosmetic Center, at Massachusetts General Hospital, Boston, said in the statement. “The complexity of facial anatomy requires in-depth knowledge and expertise, and patients should always have medical procedures done by a physician who also has knowledge of adverse events,” he added, urging consumers to see a board-certified dermatologist before undergoing any cosmetic procedure.

In response to a query, an FDA spokesperson did not have an estimate of the number of reports of these adverse events.

People who have problems or are concerned about having had a filler injected with a needle-free device should contact a licensed health care provider. Consumers and health care professionals should report adverse events related to injection of fillers with a needle-free device to the FDA’s MedWatch program. In addition to MedWatch, adverse events can also be reported to the Cutaneous Procedures Adverse Events Reporting (CAPER) Registry, established earlier this year by the ASDSA with the department of dermatology at Northwestern University, Chicago.

*This story was updated on October 12. 

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

The presence of benzene has prompted voluntary company recalls of antifungal foot sprays and sunscreen products, all aerosol spray products.

mark wragg/iStockphoto.com

Bayer has voluntarily recalled batches of its Lotrimin and Tinactin products because of benzene detected in some samples, according to an Oct. 1 company announcement, available on the Food and Drug Administration website. “It is important to note that Bayer’s decision to voluntarily recall these products is a precautionary measure and that the levels detected are not expected to cause adverse health consequences in consumers,” the announcement said.

Benzene is classified as a human carcinogen present in the environment from both natural sources and human activity, and it has been shown to cause cancer with long-term exposure.

The products included in the recall – all in aerosol spray cans – are unexpired Lotrimin and Tinactin sprays with lot numbers starting with TN, CV, or NAA that were distributed to consumer venues between September 2018 and September 2021. The over-the-counter products are Lotrimin Anti-Fungal Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal Jock Itch (AFJI) Athlete’s Foot Powder Spray, Lotrimin Anti-Fungal (AF) Athlete’s Foot Deodorant Powder Spray, Lotrimin AF Athlete’s Foot Liquid Spray, Lotrimin AF Athlete’s Foot Daily Prevention Deodorant Powder Spray, Tinactin Jock Itch (JI) Powder Spray, Tinactin Athlete’s Foot Deodorant Powder Spray, Tinactin Athlete’s Foot Powder Spray, and Tinactin Athlete’s Foot Liquid Spray.

Bayer has received no reports of adverse events related to the recall. The company also reported no concerns with its antifungal creams or other products.

In addition, Coppertone has issued a voluntary recall of specific lots of five spray sunscreen products because of the presence of benzene, according to a Sept. 30th company announcement, also posted on the FDA website. The recall includes Pure&Simple spray for babies, children, and adults; Coppertone Sport Mineral Spray; and Travel-sized Coppertone Sport spray. The specific lots were manufactured between January and June 2021, and are listed on the company announcement.

“Daily exposure to benzene at the levels detected in these affected Coppertone aerosol sunscreen spray products would not be expected to cause adverse health consequences based on generally accepted exposure modeling by numerous regulatory agencies,” according to the announcement. Coppertone has received no reports of adverse events related to the recall.

In the announcement, Coppertone advised consumers to discontinue use of the impacted products, dispose of the aerosol cans properly, and contact their physician or health care provider if they experience any problems related to the sunscreen sprays.

In May 2021, online pharmacy Valisure, which routinely tests their medications, petitioned the FDA to recall specific sunscreens after detecting high benzene levels in several brands and batches of sunscreen products. The FDA evaluated the petition, but the agency itself did not issue any recalls of sunscreens.

Clinicians are advised to report any adverse events to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail or fax using this form.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

pxfuel

We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

pxfuel

We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.

Music plus mushrooms equals therapy

Magic mushrooms have been used recreationally and medicinally for thousands of years, but researchers have found adding music could be a game changer in antidepressant treatment.

chrissmith12/Pixabay

The ingredient that makes these mushrooms so magical is psilocybin. It works well for the clinical treatment of mental health conditions and some forms of depression because the “trip” can be contained to one work day, making it easy to administer under supervision. With the accompaniment of music, scientists have found that psilocybin evokes emotion.

This recent study, presented at the European College of Neuropsychopharmacology Congress in Lisbon, tested participants’ emotional response to music before and after the psilocybin. Ketanserin, an antihypertensive drug, was used to test against the effects of psilocybin. The scientist played Mozart and Elgar and found that participants on psilocybin had an emotional response increase of 60%. That response was even greater, compared with ketanserin, which actually lessened the emotional response to music.

“This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use,” said lead researcher Dea Siggaard Stenbæk of the University of Copenhagen.

Professor David J. Nutt of Imperial College in London, who was not involved in the study, said that it supports the use of music for treatment efficacy with psychedelics and suggested that the next step is to “optimise this approach probably through individualising and personalising music tracks in therapy.”

Cue the 1960s LSD music montage.
 

Chicken ‘white striping is not a disease’

Have you ever sliced open a new pack of chicken breasts to start dinner and noticed white fatty lines running through the chicken? Maybe you thought it was just some extra fat to trim off, but the Humane League calls it “white striping disease.”

rawpixel

Chicken is the No. 1 meat consumed by Americans, so it’s not surprising that chickens are factory farmed and raised to be ready for slaughter quickly, according to CBSNews.com, which reported that the Humane League claims white striping is found in 70% of the chicken in popular grocery stores. The league expressed concern for the chickens’ welfare as they are bred to grow bigger quickly, which is causing the white striping and increasing the fat content of the meat by as much as 224%.

The National Chicken Council told CBS that the league’s findings were unscientific. A spokesperson said, “White striping is not a disease. It is a quality factor in chicken breast meat caused by deposits of fat in the muscle during the bird’s growth and development.” He went on to say that severe white striping happens in 3%-6% of birds, which are mostly used in further processed products, not in chicken breast packages.

Somehow, that’s not making us feel any better.
 

The itsy bitsy spider lets us all down

Most people do not like spiders. That’s too bad, because spiders are generally nothing but helpful little creatures that prey upon annoying flies and other pests. Then there’s the silk they produce. The ancient Romans used it to treat conditions such as warts and skin lesions. Spiders wrap their eggs in silk to protect them from harmful bacteria.

Simon Fruergaard

Of course, we can hardly trust the medical opinions of people from 2,000 years ago, but modern-day studies have not definitively proved whether or not spider silk has any antimicrobial properties.

To settle the matter once and for all, researchers from Denmark built a silk-harvesting machine using the most famous of Danish inventions: Legos. The contraption, sort of a paddle wheel, pulled the silk from several different species of spider pinned down by the researchers. The silk was then tested against three different bacteria species, including good old Escherichia coli.

Unfortunately for our spider friends, their silk has no antimicrobial activity. The researchers suspected that any such activity seen in previous studies was actually caused by improper control for the solvents used to extract the silk; those solvents can have antimicrobial properties on their own. As for protecting their eggs, rather than killing bacteria, the silk likely provides a physical barrier alone.

It is bad news for spiders on the benefit-to-humanity front, but look at the bright side: If their silk had antimicrobial activity, we’d have to start farming them to acquire more silk. And that’s no good. Spiders deserve to roam free, hunt as they please, and drop down on your head from the ceiling.
 

Anxiety and allergies: Cause, effect, confusion

We’re big fans of science, but as longtime, totally impartial (Science rules!) observers of science’s medical realm, we can see that the day-to-day process of practicing the scientific method occasionally gets a bit messy. And no, we’re not talking about COVID-19.

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We’re talking allergies. We’re talking mental health. We’re talking allergic disease and mental health.

We’re talking about a pair of press releases we came across during our never-ending search for material to educate, entertain, and astound our fabulously wonderful and loyal readers. (We say that, of course, in the most impartial way possible.)

The first release was titled, “Allergies including asthma and hay fever not linked to mental health traits” and covered research from the University of Bristol (England). The investigators were trying to determine if “allergic diseases actually causes mental health traits including anxiety, depression, bipolar disorder, and schizophrenia, or vice versa,” according to the release.

What they found, however, was “little evidence of a causal relationship between the onset of allergic disease and mental health.” Again, this is the press release talking.

The second release seemed to suggest the exact opposite: “Study uncovers link between allergies and mental health conditions.” That got our attention. A little more reading revealed that “people with asthma, atopic dermatitis, and hay fever also had a higher likelihood of having depression, anxiety, bipolar disorder, or neuroticism.”

One of the investigators was quoted as saying, “Establishing whether allergic disease causes mental health problems, or vice versa, is important to ensure that resources and treatment strategies are targeted appropriately.”

Did you notice the “vice versa”? Did you notice that it appeared in quotes from both releases? We did, so we took a closer look at the source. The second release covered a group of investigators from the University of Bristol – the same group, and the same study, in fact, as the first one.

So there you have it. One study, two press releases, and one confused journalist. Thank you, science.