MDedge Dermatology

The Centers for Disease Control and Prevention on Sept. 1 approved the use of vaccines designed to target both Omicron and the older variants of the coronavirus, a step that may aid a goal of a widespread immunization campaign before winter arrives in the United States.

The CDC’s Advisory Committee on Immunization Practices voted 13-1 on two separate questions. One sought the panel’s backing for the use of a single dose of a new version of the Pfizer COVID-19 vaccines for people aged 12 and older. The second question dealt with a single dose of the reworked Moderna vaccine for people aged 18 and older.

The federal government wants to speed use of revamped COVID-19 shots, which the Food and Drug Administration on Sept. 1 cleared for use in the United States. Hours later, CDC Director Rochelle Walensky, MD, agreed with the panel’s recommendation. 

“The updated COVID-19 boosters are formulated to better protect against the most recently circulating COVID-19 variant,” Dr. Walensky said in a statement. “They can help restore protection that has waned since previous vaccination and were designed to provide broader protection against newer variants. This recommendation followed a comprehensive scientific evaluation and robust scientific discussion. If you are eligible, there is no bad time to get your COVID-19 booster and I strongly encourage you to receive it.”

The FDA vote on Aug. 31 expanded the emergency use authorization EUA for both Moderna and Pfizer’s original COVID-19 vaccines. The new products are also called “updated boosters.” Both contain two mRNA components of SARS-CoV-2 virus, one of the original strain  and another that is found in the BA.4 and BA.5 strains of the Omicron variant, the FDA said.

Basically, the FDA cleared the way for these new boosters after it relied heavily on results of certain blood tests that suggested an immune response boost from the new formulas, plus 18 months of mostly safe use of the original versions of the shots.

What neither the FDA nor the CDC has, however, is evidence from studies in humans on how well these new vaccines work or whether they are as safe as the originals. But the FDA did consider clinical evidence for the older shots and results from studies on the new boosters that were done in mice.

ACIP Committee member Pablo Sanchez, MD, of Ohio State University was the sole “no” vote on each question.  

“It’s a new vaccine, it’s a new platform. There’s a lot of hesitancy already. We need the human data,”  Dr. Sanchez said.

Dr. Sanchez did not doubt that the newer versions of the vaccine would prove safe.

“I personally am in the age group where I’m at high risk and I’m almost sure that I will receive it,” Dr. Sanchez said. “I just feel that this was a bit premature, and I wish that we had seen that data. Having said that, I am comfortable that the vaccine will likely be safe like the others.”

Dr. Sanchez was not alone in raising concerns about backing new COVID-19 shots for which there is not direct clinical evidence from human studies.

Committee member Sarah Long, MD, of Drexel University in Philadelphia, said during the discussion she would “reluctantly” vote in favor of the updated vaccines. She said she believes they will have the potential to reduce hospitalizations and even deaths, even with questions remaining about the data.

Dr. Long joined other committee members in pointing to the approach to updating flu vaccines as a model. In an attempt to keep ahead of influenza, companies seek to defeat new strains through tweaks to their FDA-approved vaccines. There is not much clinical information available about these revised products, Dr. Long said. She compared it to remodeling an existing home.

“It is the same scaffolding, part of the same roof, we’re just putting in some dormers and windows,” with the revisions to the flu vaccine, she said.

Earlier in the day, committee member Jamie Loehr, MD,  of Cayuga Family Medicine in Ithaca, N.Y., also used changes to the annual flu shots as the model for advancing COVID-19 shots.

“So after thinking about it, I am comfortable even though we don’t have human data,” he said.

There were several questions during the meeting about why the FDA had not convened a meeting of its Vaccines and Related Biological Products Advisory Committee (regarding these specific bivalent vaccines). Typically, the FDA committee of advisers considers new vaccines before the agency authorizes their use. In this case, however, the agency acted on its own.

The FDA said the committee considered the new, bivalent COVID-19 boosters in earlier meetings and that was enough outside feedback.

But holding a meeting of advisers on these specific products could have helped build public confidence in these medicines, Dorit Reiss, PhD, of the University of California Hastings College of Law, said during the public comment session of the CDC advisers’ meeting.

“We could wish the vaccines were more effective against infection, but they’re safe and they prevent hospitalization and death,” she said.

The Department of Health and Human Services anticipated the backing of ACIP. The Administration for Strategic Preparedness and Response  on Aug. 31 began distributing “millions of doses of the updated booster to tens of thousands of sites nationwide,” Jason Roos, PhD,  chief operating officer for HHS Coordination Operations and Response Element, wrote in a blog.

“These boosters will be available at tens of thousands of vaccination sites ... including local pharmacies, their physicians’ offices, and vaccine centers operated by state and local health officials,”Dr. Roos wrote.

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

The Centers for Disease Control and Prevention on Sept. 1 approved the use of vaccines designed to target both Omicron and the older variants of the coronavirus, a step that may aid a goal of a widespread immunization campaign before winter arrives in the United States.

The CDC’s Advisory Committee on Immunization Practices voted 13-1 on two separate questions. One sought the panel’s backing for the use of a single dose of a new version of the Pfizer COVID-19 vaccines for people aged 12 and older. The second question dealt with a single dose of the reworked Moderna vaccine for people aged 18 and older.

The federal government wants to speed use of revamped COVID-19 shots, which the Food and Drug Administration on Sept. 1 cleared for use in the United States. Hours later, CDC Director Rochelle Walensky, MD, agreed with the panel’s recommendation. 

“The updated COVID-19 boosters are formulated to better protect against the most recently circulating COVID-19 variant,” Dr. Walensky said in a statement. “They can help restore protection that has waned since previous vaccination and were designed to provide broader protection against newer variants. This recommendation followed a comprehensive scientific evaluation and robust scientific discussion. If you are eligible, there is no bad time to get your COVID-19 booster and I strongly encourage you to receive it.”

The FDA vote on Aug. 31 expanded the emergency use authorization EUA for both Moderna and Pfizer’s original COVID-19 vaccines. The new products are also called “updated boosters.” Both contain two mRNA components of SARS-CoV-2 virus, one of the original strain  and another that is found in the BA.4 and BA.5 strains of the Omicron variant, the FDA said.

Basically, the FDA cleared the way for these new boosters after it relied heavily on results of certain blood tests that suggested an immune response boost from the new formulas, plus 18 months of mostly safe use of the original versions of the shots.

What neither the FDA nor the CDC has, however, is evidence from studies in humans on how well these new vaccines work or whether they are as safe as the originals. But the FDA did consider clinical evidence for the older shots and results from studies on the new boosters that were done in mice.

ACIP Committee member Pablo Sanchez, MD, of Ohio State University was the sole “no” vote on each question.  

“It’s a new vaccine, it’s a new platform. There’s a lot of hesitancy already. We need the human data,”  Dr. Sanchez said.

Dr. Sanchez did not doubt that the newer versions of the vaccine would prove safe.

“I personally am in the age group where I’m at high risk and I’m almost sure that I will receive it,” Dr. Sanchez said. “I just feel that this was a bit premature, and I wish that we had seen that data. Having said that, I am comfortable that the vaccine will likely be safe like the others.”

Dr. Sanchez was not alone in raising concerns about backing new COVID-19 shots for which there is not direct clinical evidence from human studies.

Committee member Sarah Long, MD, of Drexel University in Philadelphia, said during the discussion she would “reluctantly” vote in favor of the updated vaccines. She said she believes they will have the potential to reduce hospitalizations and even deaths, even with questions remaining about the data.

Dr. Long joined other committee members in pointing to the approach to updating flu vaccines as a model. In an attempt to keep ahead of influenza, companies seek to defeat new strains through tweaks to their FDA-approved vaccines. There is not much clinical information available about these revised products, Dr. Long said. She compared it to remodeling an existing home.

“It is the same scaffolding, part of the same roof, we’re just putting in some dormers and windows,” with the revisions to the flu vaccine, she said.

Earlier in the day, committee member Jamie Loehr, MD,  of Cayuga Family Medicine in Ithaca, N.Y., also used changes to the annual flu shots as the model for advancing COVID-19 shots.

“So after thinking about it, I am comfortable even though we don’t have human data,” he said.

There were several questions during the meeting about why the FDA had not convened a meeting of its Vaccines and Related Biological Products Advisory Committee (regarding these specific bivalent vaccines). Typically, the FDA committee of advisers considers new vaccines before the agency authorizes their use. In this case, however, the agency acted on its own.

The FDA said the committee considered the new, bivalent COVID-19 boosters in earlier meetings and that was enough outside feedback.

But holding a meeting of advisers on these specific products could have helped build public confidence in these medicines, Dorit Reiss, PhD, of the University of California Hastings College of Law, said during the public comment session of the CDC advisers’ meeting.

“We could wish the vaccines were more effective against infection, but they’re safe and they prevent hospitalization and death,” she said.

The Department of Health and Human Services anticipated the backing of ACIP. The Administration for Strategic Preparedness and Response  on Aug. 31 began distributing “millions of doses of the updated booster to tens of thousands of sites nationwide,” Jason Roos, PhD,  chief operating officer for HHS Coordination Operations and Response Element, wrote in a blog.

“These boosters will be available at tens of thousands of vaccination sites ... including local pharmacies, their physicians’ offices, and vaccine centers operated by state and local health officials,”Dr. Roos wrote.

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

The Centers for Disease Control and Prevention on Sept. 1 approved the use of vaccines designed to target both Omicron and the older variants of the coronavirus, a step that may aid a goal of a widespread immunization campaign before winter arrives in the United States.

The CDC’s Advisory Committee on Immunization Practices voted 13-1 on two separate questions. One sought the panel’s backing for the use of a single dose of a new version of the Pfizer COVID-19 vaccines for people aged 12 and older. The second question dealt with a single dose of the reworked Moderna vaccine for people aged 18 and older.

The federal government wants to speed use of revamped COVID-19 shots, which the Food and Drug Administration on Sept. 1 cleared for use in the United States. Hours later, CDC Director Rochelle Walensky, MD, agreed with the panel’s recommendation. 

“The updated COVID-19 boosters are formulated to better protect against the most recently circulating COVID-19 variant,” Dr. Walensky said in a statement. “They can help restore protection that has waned since previous vaccination and were designed to provide broader protection against newer variants. This recommendation followed a comprehensive scientific evaluation and robust scientific discussion. If you are eligible, there is no bad time to get your COVID-19 booster and I strongly encourage you to receive it.”

The FDA vote on Aug. 31 expanded the emergency use authorization EUA for both Moderna and Pfizer’s original COVID-19 vaccines. The new products are also called “updated boosters.” Both contain two mRNA components of SARS-CoV-2 virus, one of the original strain  and another that is found in the BA.4 and BA.5 strains of the Omicron variant, the FDA said.

Basically, the FDA cleared the way for these new boosters after it relied heavily on results of certain blood tests that suggested an immune response boost from the new formulas, plus 18 months of mostly safe use of the original versions of the shots.

What neither the FDA nor the CDC has, however, is evidence from studies in humans on how well these new vaccines work or whether they are as safe as the originals. But the FDA did consider clinical evidence for the older shots and results from studies on the new boosters that were done in mice.

ACIP Committee member Pablo Sanchez, MD, of Ohio State University was the sole “no” vote on each question.  

“It’s a new vaccine, it’s a new platform. There’s a lot of hesitancy already. We need the human data,”  Dr. Sanchez said.

Dr. Sanchez did not doubt that the newer versions of the vaccine would prove safe.

“I personally am in the age group where I’m at high risk and I’m almost sure that I will receive it,” Dr. Sanchez said. “I just feel that this was a bit premature, and I wish that we had seen that data. Having said that, I am comfortable that the vaccine will likely be safe like the others.”

Dr. Sanchez was not alone in raising concerns about backing new COVID-19 shots for which there is not direct clinical evidence from human studies.

Committee member Sarah Long, MD, of Drexel University in Philadelphia, said during the discussion she would “reluctantly” vote in favor of the updated vaccines. She said she believes they will have the potential to reduce hospitalizations and even deaths, even with questions remaining about the data.

Dr. Long joined other committee members in pointing to the approach to updating flu vaccines as a model. In an attempt to keep ahead of influenza, companies seek to defeat new strains through tweaks to their FDA-approved vaccines. There is not much clinical information available about these revised products, Dr. Long said. She compared it to remodeling an existing home.

“It is the same scaffolding, part of the same roof, we’re just putting in some dormers and windows,” with the revisions to the flu vaccine, she said.

Earlier in the day, committee member Jamie Loehr, MD,  of Cayuga Family Medicine in Ithaca, N.Y., also used changes to the annual flu shots as the model for advancing COVID-19 shots.

“So after thinking about it, I am comfortable even though we don’t have human data,” he said.

There were several questions during the meeting about why the FDA had not convened a meeting of its Vaccines and Related Biological Products Advisory Committee (regarding these specific bivalent vaccines). Typically, the FDA committee of advisers considers new vaccines before the agency authorizes their use. In this case, however, the agency acted on its own.

The FDA said the committee considered the new, bivalent COVID-19 boosters in earlier meetings and that was enough outside feedback.

But holding a meeting of advisers on these specific products could have helped build public confidence in these medicines, Dorit Reiss, PhD, of the University of California Hastings College of Law, said during the public comment session of the CDC advisers’ meeting.

“We could wish the vaccines were more effective against infection, but they’re safe and they prevent hospitalization and death,” she said.

The Department of Health and Human Services anticipated the backing of ACIP. The Administration for Strategic Preparedness and Response  on Aug. 31 began distributing “millions of doses of the updated booster to tens of thousands of sites nationwide,” Jason Roos, PhD,  chief operating officer for HHS Coordination Operations and Response Element, wrote in a blog.

“These boosters will be available at tens of thousands of vaccination sites ... including local pharmacies, their physicians’ offices, and vaccine centers operated by state and local health officials,”Dr. Roos wrote.

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

PORTLAND, ORE. – When individuals with skin of color seek help from dermatologists to optimize the treatment and management of scalp and hair disorders, they expect them to understand their concerns, but sometimes their doctors fall short.

“Many times, you may not have race concordant visits with patients of color,” Janiene Luke, MD, said at the annual meeting of the Pacific Dermatologic Association. She referred to a survey of 200 Black women aged 21-83 years, which found that 28% had visited a physician to discuss hair or scalp issues. Of those, 68% felt like their dermatologists did not understand African American hair.

“I recommend trying the best you can to familiarize yourself with various common cultural hair styling methods and practices in patients of color. It’s important to understand what your patients are engaging in and the types of styles they’re using,” said Dr. Luke, associate professor of dermatology at Loma Linda (Calif.) University. “Approach all patients with cultural humility. We know from studies that patients value dermatologists who take time to listen to their concerns, involve them in the decision-making process, and educate them about their conditions,” she added.

National efforts to educate clinicians on treating skin of color have emerged in recent years, including textbooks, CME courses at dermatology conferences, and the American Academy of Dermatology’s Skin of Color Curriculum, which consists of 15-minute modules that can be viewed online.

At the meeting, Dr. Luke, shared her approach to assessing hair and scalp disorders in skin of color. She begins by taking a thorough history, “because not all things that are associated with hair styling will be the reason why your patient comes in,” she said. “Patients of color can have telogen effluvium and seborrheic dermatitis just like anyone else. I ask about the hair styling practices they use. I also ask how often they wash their hair, because sometimes our recommendations for treatment are not realistic based on their current routine.”

Next, she examines the scalp with her hands – which sometimes surprises patients. “I’ve had so many patients come in and say, ‘the dermatologist never touched my scalp,’ or ‘they never even looked at my hair,’ ” said Dr. Luke, who directs the university’s dermatology residency program. She asks patients to remove any hair extensions or weaves prior to the office visit and to remove wigs prior to the exam itself. The lab tests she customarily orders include CBC, TSH, iron, total iron binding capacity, ferritin, vitamin D, and zinc. If there are signs of androgen excess, she may check testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate (DHEA-S). She routinely incorporates a dermoscopy-directed biopsy into the evaluation.

Dr. Luke examines the patient from above, the sides, and the back to assess the pattern/distribution of hair loss. A visible scalp at the vertex indicates a 50% reduction in normal hair density. “I’m looking at the hairline, their part width, and the length of their hair,” she said. “I also look at the eyebrows and eyelashes, because these can be involved in alopecia areata, frontal fibrosing alopecia, or congenital hair shaft disorders.”

On closeup examination, she looks for scarring versus non-scarring types of hair loss, and for the presence or absence of follicular ostia. “I also look at hair changes,” she said. “Is the texture of their hair different? Are there signs of breakage or fragility? It’s been noted in studies that breakage can be an early sign of central centrifugal cicatricial alopecia.” (For more tips on examining tightly coiled hair among patients with hair loss in race discordant patient-physician interactions, she recommended a 2021 article in JAMA Dermatology)..

Trichoscopy allows for magnified observation of the hair shafts, hair follicle openings, perifollicular dermis, and blood vessels. Normal trichoscopy findings in skin of color reveal a perifollicular pigment network (honeycomb pattern) and pinpoint white dots that are regularly distributed between follicular units.

Common abnormalities seen on trichoscopy include central centrifugal cicatricial alopecia (CCCA), with one or two hairs emerging together, surrounded by a gray halo; lichen planopilaris/frontal fibrosing alopecia, characterized by hair with peripilar casts and absence of vellus hairs; discoid lupus erythematosus, characterized by keratotic plugs; and traction, characterized by hair casts.

Once a diagnosis is confirmed, Dr. Luke provides other general advice for optimal skin health, including a balanced (whole food) diet to ensure adequate nutrition. “I tend to find a lot of nutrient deficiencies that contribute to and compound their condition,” she said. Other recommendations include avoiding excess tension on the hair, such as hair styles with tight ponytails, buns, braids, and weaves; avoiding or limiting chemical treatments with hair color, relaxers, and permanents; and avoiding or limiting excessive heat styling with blow dryers, flat irons, and curling irons.


 

Photoprotection misconceptions

At the meeting, Dr. Luke also discussed three misconceptions of photoprotection in skin of color, drawn from an article on the topic published in 2021.

• Myth No. 1: Endogenous melanin provides complete photoprotection for Fitzpatrick skin types IV-V. Many people with skin of color may believe sunscreen is not needed given the melanin already present in their skin, but research has shown that the epidermis of dark skin has an intrinsic sun protection factor (SPF) of 13.4, compared with an SPF of 3.3 in light skin. “That may not provide them with full protection,” Dr. Luke said. “Many dermatologists are not counseling their skin of color patients about photoprotection.”
• Myth No. 2: Individuals with skin of color have negligible risks associated with skin cancer. Skin cancer prevalence in patients with skin of color is significantly lower compared with those with light skin. However, people with skin of color tend to be diagnosed with cancers at a more advanced stage, and cancers associated with a worse prognosis and poorer survival rate. An analysis of ethnic differences among patients with cutaneous melanoma that drew from the Surveillance, Epidemiology, and End Results (SEER) program found that Hispanic individuals (odds ratio [OR], 3.6), Black individuals (OR, 4.2), and Asian individuals (OR, 2.4), were more likely than were White individuals to have stage IV melanoma at the time of presentation. “For melanoma in skin of color, UV radiation does not seem to be a major risk factor, as melanoma tends to occur on palmar/plantar and subungual skin as well as mucous membranes,” Dr. Luke said. “For squamous cell carcinoma in skin of color, lesions are more likely to be present in areas that are not sun exposed. The risk factors for this tend to be chronic wounds, nonhealing ulcers, and people with chronic inflammatory conditions.” For basal cell carcinoma, she added, UV radiation seems to play more of a role and tends to occur in sun-exposed areas in patients with lighter Fitzpatrick skin types. Patients are more likely to present with pigmented BCCs.

• Myth No. 3: Broad-spectrum sunscreens provide photoprotection against all wavelengths of light that cause skin damage. To be labeled “broad-spectrum” the Food and Drug Administration requires that sunscreens have a critical wavelength of 370 nm or below, but Dr. Luke noted that broad-spectrum sunscreens do not necessarily protect against visible light (VL) and UV-A1. Research has demonstrated that VL exposure induces both transient and long-term cutaneous pigmentation in a dose-dependent manner.

“This induces free radicals and reactive oxygen species, leading to a cascade of events including the induction of pro-inflammatory cytokines, matrix metalloproteinases, and melanogenesis,” she said. “More intense and persistent VL-induced pigmentation occurs in subjects with darker skin. However, there is increasing evidence that antioxidants may help to mitigate these negative effects, so we are starting to see the addition of antioxidants into sunscreens.”

Dr. Luke recommends a broad-spectrum sunscreen with an SPF of 30 or higher for skin of color patients. Tinted sunscreens, which contain iron oxide pigments, are recommended for the prevention and treatment of pigmentary disorders in patients with Fitzpatrick skin types IV-VI skin. “What about adding antioxidants to prevent formation of reactive oxygen species?” she asked. “It’s possible but we don’t have a lot of research yet. You also want a sunscreen that’s aesthetically elegant, meaning it doesn’t leave a white cast.”

Dr. Luke reported having no relevant disclosures.

PORTLAND, ORE. – When individuals with skin of color seek help from dermatologists to optimize the treatment and management of scalp and hair disorders, they expect them to understand their concerns, but sometimes their doctors fall short.

“Many times, you may not have race concordant visits with patients of color,” Janiene Luke, MD, said at the annual meeting of the Pacific Dermatologic Association. She referred to a survey of 200 Black women aged 21-83 years, which found that 28% had visited a physician to discuss hair or scalp issues. Of those, 68% felt like their dermatologists did not understand African American hair.

“I recommend trying the best you can to familiarize yourself with various common cultural hair styling methods and practices in patients of color. It’s important to understand what your patients are engaging in and the types of styles they’re using,” said Dr. Luke, associate professor of dermatology at Loma Linda (Calif.) University. “Approach all patients with cultural humility. We know from studies that patients value dermatologists who take time to listen to their concerns, involve them in the decision-making process, and educate them about their conditions,” she added.

National efforts to educate clinicians on treating skin of color have emerged in recent years, including textbooks, CME courses at dermatology conferences, and the American Academy of Dermatology’s Skin of Color Curriculum, which consists of 15-minute modules that can be viewed online.

At the meeting, Dr. Luke, shared her approach to assessing hair and scalp disorders in skin of color. She begins by taking a thorough history, “because not all things that are associated with hair styling will be the reason why your patient comes in,” she said. “Patients of color can have telogen effluvium and seborrheic dermatitis just like anyone else. I ask about the hair styling practices they use. I also ask how often they wash their hair, because sometimes our recommendations for treatment are not realistic based on their current routine.”

Next, she examines the scalp with her hands – which sometimes surprises patients. “I’ve had so many patients come in and say, ‘the dermatologist never touched my scalp,’ or ‘they never even looked at my hair,’ ” said Dr. Luke, who directs the university’s dermatology residency program. She asks patients to remove any hair extensions or weaves prior to the office visit and to remove wigs prior to the exam itself. The lab tests she customarily orders include CBC, TSH, iron, total iron binding capacity, ferritin, vitamin D, and zinc. If there are signs of androgen excess, she may check testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate (DHEA-S). She routinely incorporates a dermoscopy-directed biopsy into the evaluation.

Dr. Luke examines the patient from above, the sides, and the back to assess the pattern/distribution of hair loss. A visible scalp at the vertex indicates a 50% reduction in normal hair density. “I’m looking at the hairline, their part width, and the length of their hair,” she said. “I also look at the eyebrows and eyelashes, because these can be involved in alopecia areata, frontal fibrosing alopecia, or congenital hair shaft disorders.”

On closeup examination, she looks for scarring versus non-scarring types of hair loss, and for the presence or absence of follicular ostia. “I also look at hair changes,” she said. “Is the texture of their hair different? Are there signs of breakage or fragility? It’s been noted in studies that breakage can be an early sign of central centrifugal cicatricial alopecia.” (For more tips on examining tightly coiled hair among patients with hair loss in race discordant patient-physician interactions, she recommended a 2021 article in JAMA Dermatology)..

Trichoscopy allows for magnified observation of the hair shafts, hair follicle openings, perifollicular dermis, and blood vessels. Normal trichoscopy findings in skin of color reveal a perifollicular pigment network (honeycomb pattern) and pinpoint white dots that are regularly distributed between follicular units.

Common abnormalities seen on trichoscopy include central centrifugal cicatricial alopecia (CCCA), with one or two hairs emerging together, surrounded by a gray halo; lichen planopilaris/frontal fibrosing alopecia, characterized by hair with peripilar casts and absence of vellus hairs; discoid lupus erythematosus, characterized by keratotic plugs; and traction, characterized by hair casts.

Once a diagnosis is confirmed, Dr. Luke provides other general advice for optimal skin health, including a balanced (whole food) diet to ensure adequate nutrition. “I tend to find a lot of nutrient deficiencies that contribute to and compound their condition,” she said. Other recommendations include avoiding excess tension on the hair, such as hair styles with tight ponytails, buns, braids, and weaves; avoiding or limiting chemical treatments with hair color, relaxers, and permanents; and avoiding or limiting excessive heat styling with blow dryers, flat irons, and curling irons.


 

Photoprotection misconceptions

At the meeting, Dr. Luke also discussed three misconceptions of photoprotection in skin of color, drawn from an article on the topic published in 2021.

• Myth No. 1: Endogenous melanin provides complete photoprotection for Fitzpatrick skin types IV-V. Many people with skin of color may believe sunscreen is not needed given the melanin already present in their skin, but research has shown that the epidermis of dark skin has an intrinsic sun protection factor (SPF) of 13.4, compared with an SPF of 3.3 in light skin. “That may not provide them with full protection,” Dr. Luke said. “Many dermatologists are not counseling their skin of color patients about photoprotection.”
• Myth No. 2: Individuals with skin of color have negligible risks associated with skin cancer. Skin cancer prevalence in patients with skin of color is significantly lower compared with those with light skin. However, people with skin of color tend to be diagnosed with cancers at a more advanced stage, and cancers associated with a worse prognosis and poorer survival rate. An analysis of ethnic differences among patients with cutaneous melanoma that drew from the Surveillance, Epidemiology, and End Results (SEER) program found that Hispanic individuals (odds ratio [OR], 3.6), Black individuals (OR, 4.2), and Asian individuals (OR, 2.4), were more likely than were White individuals to have stage IV melanoma at the time of presentation. “For melanoma in skin of color, UV radiation does not seem to be a major risk factor, as melanoma tends to occur on palmar/plantar and subungual skin as well as mucous membranes,” Dr. Luke said. “For squamous cell carcinoma in skin of color, lesions are more likely to be present in areas that are not sun exposed. The risk factors for this tend to be chronic wounds, nonhealing ulcers, and people with chronic inflammatory conditions.” For basal cell carcinoma, she added, UV radiation seems to play more of a role and tends to occur in sun-exposed areas in patients with lighter Fitzpatrick skin types. Patients are more likely to present with pigmented BCCs.

• Myth No. 3: Broad-spectrum sunscreens provide photoprotection against all wavelengths of light that cause skin damage. To be labeled “broad-spectrum” the Food and Drug Administration requires that sunscreens have a critical wavelength of 370 nm or below, but Dr. Luke noted that broad-spectrum sunscreens do not necessarily protect against visible light (VL) and UV-A1. Research has demonstrated that VL exposure induces both transient and long-term cutaneous pigmentation in a dose-dependent manner.

“This induces free radicals and reactive oxygen species, leading to a cascade of events including the induction of pro-inflammatory cytokines, matrix metalloproteinases, and melanogenesis,” she said. “More intense and persistent VL-induced pigmentation occurs in subjects with darker skin. However, there is increasing evidence that antioxidants may help to mitigate these negative effects, so we are starting to see the addition of antioxidants into sunscreens.”

Dr. Luke recommends a broad-spectrum sunscreen with an SPF of 30 or higher for skin of color patients. Tinted sunscreens, which contain iron oxide pigments, are recommended for the prevention and treatment of pigmentary disorders in patients with Fitzpatrick skin types IV-VI skin. “What about adding antioxidants to prevent formation of reactive oxygen species?” she asked. “It’s possible but we don’t have a lot of research yet. You also want a sunscreen that’s aesthetically elegant, meaning it doesn’t leave a white cast.”

Dr. Luke reported having no relevant disclosures.

PORTLAND, ORE. – When individuals with skin of color seek help from dermatologists to optimize the treatment and management of scalp and hair disorders, they expect them to understand their concerns, but sometimes their doctors fall short.

“Many times, you may not have race concordant visits with patients of color,” Janiene Luke, MD, said at the annual meeting of the Pacific Dermatologic Association. She referred to a survey of 200 Black women aged 21-83 years, which found that 28% had visited a physician to discuss hair or scalp issues. Of those, 68% felt like their dermatologists did not understand African American hair.

“I recommend trying the best you can to familiarize yourself with various common cultural hair styling methods and practices in patients of color. It’s important to understand what your patients are engaging in and the types of styles they’re using,” said Dr. Luke, associate professor of dermatology at Loma Linda (Calif.) University. “Approach all patients with cultural humility. We know from studies that patients value dermatologists who take time to listen to their concerns, involve them in the decision-making process, and educate them about their conditions,” she added.

National efforts to educate clinicians on treating skin of color have emerged in recent years, including textbooks, CME courses at dermatology conferences, and the American Academy of Dermatology’s Skin of Color Curriculum, which consists of 15-minute modules that can be viewed online.

At the meeting, Dr. Luke, shared her approach to assessing hair and scalp disorders in skin of color. She begins by taking a thorough history, “because not all things that are associated with hair styling will be the reason why your patient comes in,” she said. “Patients of color can have telogen effluvium and seborrheic dermatitis just like anyone else. I ask about the hair styling practices they use. I also ask how often they wash their hair, because sometimes our recommendations for treatment are not realistic based on their current routine.”

Next, she examines the scalp with her hands – which sometimes surprises patients. “I’ve had so many patients come in and say, ‘the dermatologist never touched my scalp,’ or ‘they never even looked at my hair,’ ” said Dr. Luke, who directs the university’s dermatology residency program. She asks patients to remove any hair extensions or weaves prior to the office visit and to remove wigs prior to the exam itself. The lab tests she customarily orders include CBC, TSH, iron, total iron binding capacity, ferritin, vitamin D, and zinc. If there are signs of androgen excess, she may check testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate (DHEA-S). She routinely incorporates a dermoscopy-directed biopsy into the evaluation.

Dr. Luke examines the patient from above, the sides, and the back to assess the pattern/distribution of hair loss. A visible scalp at the vertex indicates a 50% reduction in normal hair density. “I’m looking at the hairline, their part width, and the length of their hair,” she said. “I also look at the eyebrows and eyelashes, because these can be involved in alopecia areata, frontal fibrosing alopecia, or congenital hair shaft disorders.”

On closeup examination, she looks for scarring versus non-scarring types of hair loss, and for the presence or absence of follicular ostia. “I also look at hair changes,” she said. “Is the texture of their hair different? Are there signs of breakage or fragility? It’s been noted in studies that breakage can be an early sign of central centrifugal cicatricial alopecia.” (For more tips on examining tightly coiled hair among patients with hair loss in race discordant patient-physician interactions, she recommended a 2021 article in JAMA Dermatology)..

Trichoscopy allows for magnified observation of the hair shafts, hair follicle openings, perifollicular dermis, and blood vessels. Normal trichoscopy findings in skin of color reveal a perifollicular pigment network (honeycomb pattern) and pinpoint white dots that are regularly distributed between follicular units.

Common abnormalities seen on trichoscopy include central centrifugal cicatricial alopecia (CCCA), with one or two hairs emerging together, surrounded by a gray halo; lichen planopilaris/frontal fibrosing alopecia, characterized by hair with peripilar casts and absence of vellus hairs; discoid lupus erythematosus, characterized by keratotic plugs; and traction, characterized by hair casts.

Once a diagnosis is confirmed, Dr. Luke provides other general advice for optimal skin health, including a balanced (whole food) diet to ensure adequate nutrition. “I tend to find a lot of nutrient deficiencies that contribute to and compound their condition,” she said. Other recommendations include avoiding excess tension on the hair, such as hair styles with tight ponytails, buns, braids, and weaves; avoiding or limiting chemical treatments with hair color, relaxers, and permanents; and avoiding or limiting excessive heat styling with blow dryers, flat irons, and curling irons.


 

Photoprotection misconceptions

At the meeting, Dr. Luke also discussed three misconceptions of photoprotection in skin of color, drawn from an article on the topic published in 2021.

• Myth No. 1: Endogenous melanin provides complete photoprotection for Fitzpatrick skin types IV-V. Many people with skin of color may believe sunscreen is not needed given the melanin already present in their skin, but research has shown that the epidermis of dark skin has an intrinsic sun protection factor (SPF) of 13.4, compared with an SPF of 3.3 in light skin. “That may not provide them with full protection,” Dr. Luke said. “Many dermatologists are not counseling their skin of color patients about photoprotection.”
• Myth No. 2: Individuals with skin of color have negligible risks associated with skin cancer. Skin cancer prevalence in patients with skin of color is significantly lower compared with those with light skin. However, people with skin of color tend to be diagnosed with cancers at a more advanced stage, and cancers associated with a worse prognosis and poorer survival rate. An analysis of ethnic differences among patients with cutaneous melanoma that drew from the Surveillance, Epidemiology, and End Results (SEER) program found that Hispanic individuals (odds ratio [OR], 3.6), Black individuals (OR, 4.2), and Asian individuals (OR, 2.4), were more likely than were White individuals to have stage IV melanoma at the time of presentation. “For melanoma in skin of color, UV radiation does not seem to be a major risk factor, as melanoma tends to occur on palmar/plantar and subungual skin as well as mucous membranes,” Dr. Luke said. “For squamous cell carcinoma in skin of color, lesions are more likely to be present in areas that are not sun exposed. The risk factors for this tend to be chronic wounds, nonhealing ulcers, and people with chronic inflammatory conditions.” For basal cell carcinoma, she added, UV radiation seems to play more of a role and tends to occur in sun-exposed areas in patients with lighter Fitzpatrick skin types. Patients are more likely to present with pigmented BCCs.

• Myth No. 3: Broad-spectrum sunscreens provide photoprotection against all wavelengths of light that cause skin damage. To be labeled “broad-spectrum” the Food and Drug Administration requires that sunscreens have a critical wavelength of 370 nm or below, but Dr. Luke noted that broad-spectrum sunscreens do not necessarily protect against visible light (VL) and UV-A1. Research has demonstrated that VL exposure induces both transient and long-term cutaneous pigmentation in a dose-dependent manner.

“This induces free radicals and reactive oxygen species, leading to a cascade of events including the induction of pro-inflammatory cytokines, matrix metalloproteinases, and melanogenesis,” she said. “More intense and persistent VL-induced pigmentation occurs in subjects with darker skin. However, there is increasing evidence that antioxidants may help to mitigate these negative effects, so we are starting to see the addition of antioxidants into sunscreens.”

Dr. Luke recommends a broad-spectrum sunscreen with an SPF of 30 or higher for skin of color patients. Tinted sunscreens, which contain iron oxide pigments, are recommended for the prevention and treatment of pigmentary disorders in patients with Fitzpatrick skin types IV-VI skin. “What about adding antioxidants to prevent formation of reactive oxygen species?” she asked. “It’s possible but we don’t have a lot of research yet. You also want a sunscreen that’s aesthetically elegant, meaning it doesn’t leave a white cast.”

Dr. Luke reported having no relevant disclosures.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”

Such expressions of frustration may partly stem from the fact that high acne treatment failure rates occur in women over the age of 25. In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.

In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.

Obencem/Thinkstock

Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”

When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.

Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”

All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
 

Oral contraceptives

Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”

Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.

No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.

“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.

The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”

Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.

Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
 

Spironolactone

Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.

Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.

Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”

Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.

In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.

Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.

“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”

Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.

PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”

Such expressions of frustration may partly stem from the fact that high acne treatment failure rates occur in women over the age of 25. In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.

In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.

Obencem/Thinkstock

Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”

When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.

Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”

All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
 

Oral contraceptives

Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”

Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.

No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.

“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.

The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”

Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.

Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
 

Spironolactone

Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.

Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.

Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”

Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.

In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.

Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.

“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”

Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.

PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”

Such expressions of frustration may partly stem from the fact that high acne treatment failure rates occur in women over the age of 25. In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.

In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.

Obencem/Thinkstock

Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”

When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.

Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”

All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
 

Oral contraceptives

Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”

Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.

No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.

“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.

The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”

Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.

Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
 

Spironolactone

Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.

Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.

Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”

Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.

In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.

Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.

“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”

Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

Residents are confronted daily with situations in clinic that require a foundation in medical ethics to assist in decision-making. Attending physicians require health care services and at times may seek care from resident physicians. If the attending physician has direct oversight over the resident, however, the ethics of the resident treating them need to be addressed. Although patients have autonomy to choose whoever they want as a physician, nonmaleficence dictates that the resident may forego treatment due to concerns for providing suboptimal care; however, this same attending may be treated under specific circumstances. This column explores the ethical implications of both situations.

The Ethical Dilemma of Treating an Attending

Imagine this scenario: You are in your resident general dermatology clinic seeing patients with an attending overseeing your clinical decisions following each encounter. You look on your schedule and see that the next patient is one of your pediatric dermatology attendings for a total-body skin examination (TBSE). You have never treated a physician that oversees you, and you ponder whether you should perform the examination or fetch your attending to perform the encounter alone.

This conundrum then brings other questions to mind: Would changing the reason for the appointment (ie, an acute problem vs a TBSE) alter your decision as to whether or not you would treat this attending? Would the situation be different if this was an attending in a different department?

Ethics Curriculum for Residents

Medical providers face ethical dilemmas daily, and dermatologists and dermatology residents are not excluded. Dermatoethics can provide a framework for the best approach to this hypothetical situation. To equip residents with resources on ethics and a cognitive framework to approach similar situations, the American Board of Dermatology has created an ethics curriculum for residents to learn over their 3 years of training.¹

One study that analyzed the ethical themes portrayed in essays by fourth-year medical students showed that the most common themes included autonomy, social justice, nonmaleficence, beneficence, honesty, and respect.² These themes must be considered in different permutations throughout ethical conundrums.

In the situation of an attending physician who supervises a resident in another clinic voluntarily attending the resident clinic, the physician is aware of the resident’s skills and qualifications and knows that supervision is being provided by an attending physician, which allows informed consent to be made, as a study by Unruh et al³ shows. The patient’s autonomy allows them to choose their treating provider.

However, there are several reasons why the resident may be hesitant to enter the room. One concern may be that during a TBSE the provider usually examines the patient’s genitals, rectum, and breasts.⁴ Because the resident knows the individual personally, the patient and/or the provider may be uncomfortable checking these areas, leaving a portion of the examination unperformed. This neglect may harm the patient (eg, a genital melanoma is missed), violating the tenant of nonmaleficence.

The effect of the medical hierarchy also should be considered. The de facto hierarchy of attendings supervising residents, interns, and medical students, with each group having some oversight over the next, can have positive effects on education and appropriate patient management but also can prove to be detrimental to the patient and provider in some circumstances. Studies have shown that residents may be less willing to disagree with their superior’s opinions for fear of negative reactions and harmful effects on their future careers.^5-7 The hierarchy of medicine also can affect a resident’s moral judgement by intimidating the practitioner to perform tasks or make diagnoses they may not wish to make.^5,6,8,9 For example, the resident may send a prescription for a medication that the attending requested despite no clear indication of need. This mingling of patient and supervisor roles can result in a resident treating their attending physician inconsistently with their standard of care.

Navigating the Ethics of Treating Family Members

The American Medical Association Code of Medical Ethics Opinions on Patient-Physician Relationships highlights treating family members as an important ethical topic. Although most residents and attendings are not biologically related, a familial-style relationship exists in many dermatology programs between attendings and residents due to the close-knit nature of dermatology programs. Diagnostic and treatment accuracy may be diminished by the discomfort or disbelief that a condition could affect someone the resident cares about.¹⁰

The American Medical Association also states that a physician can treat family members in an emergency situation or for short-term minor problems. If these 2 exceptions were to be extrapolated to apply to situations involving residents and attendings in addition to family, there would be situations where a dermatology resident could ethically treat their attending physician.¹⁰ If the attending physician was worried about a problem that was deemed potentially life-threatening, such as a rapidly progressive bullous eruption concerning for Stevens-Johnson syndrome following the initiation of a new medication, and they wanted an urgent evaluation and biopsy, an ethicist could argue that urgent treatment is medically indicated as deferring treatment could have negative consequences on the patient’s health. In addition, if the attending found a splinter in their finger following yardwork and needed assistance in removal, this also could be treated by their resident, as it is minimally invasive and has a finite conclusion.

Treating Nonsupervisory Attendings

In the case of performing a TBSE on an attending from another specialty, it would be acceptable and less ethically ambiguous if no close personal relationship existed between the two practitioners, as this patient would have no direct oversight over the resident physician.

Final Thoughts

Each situation that residents face may carry ethical implications with perspectives from the patient, provider, and bystanders. The above scenarios highlight specific instances that a dermatology resident may face and provide insight into how they may approach the situations. At the same time, it is important to remember that every situation is different and requires a unique approach. Fortunately,physicians—specifically dermatologists—are provided many resources to help navigate challenging scenarios.

Acknowledgments—The author thanks Jane M. Grant-Kels, MD (Farmington, Connecticut), for reviewing this paper and providing feedback to improve its content, as well as Warren R. Heymann, MD (Camden, New Jersey), for assisting in the creation of this topic and article.

Residents are confronted daily with situations in clinic that require a foundation in medical ethics to assist in decision-making. Attending physicians require health care services and at times may seek care from resident physicians. If the attending physician has direct oversight over the resident, however, the ethics of the resident treating them need to be addressed. Although patients have autonomy to choose whoever they want as a physician, nonmaleficence dictates that the resident may forego treatment due to concerns for providing suboptimal care; however, this same attending may be treated under specific circumstances. This column explores the ethical implications of both situations.

The Ethical Dilemma of Treating an Attending

Imagine this scenario: You are in your resident general dermatology clinic seeing patients with an attending overseeing your clinical decisions following each encounter. You look on your schedule and see that the next patient is one of your pediatric dermatology attendings for a total-body skin examination (TBSE). You have never treated a physician that oversees you, and you ponder whether you should perform the examination or fetch your attending to perform the encounter alone.

This conundrum then brings other questions to mind: Would changing the reason for the appointment (ie, an acute problem vs a TBSE) alter your decision as to whether or not you would treat this attending? Would the situation be different if this was an attending in a different department?

Ethics Curriculum for Residents

Medical providers face ethical dilemmas daily, and dermatologists and dermatology residents are not excluded. Dermatoethics can provide a framework for the best approach to this hypothetical situation. To equip residents with resources on ethics and a cognitive framework to approach similar situations, the American Board of Dermatology has created an ethics curriculum for residents to learn over their 3 years of training.¹

One study that analyzed the ethical themes portrayed in essays by fourth-year medical students showed that the most common themes included autonomy, social justice, nonmaleficence, beneficence, honesty, and respect.² These themes must be considered in different permutations throughout ethical conundrums.

In the situation of an attending physician who supervises a resident in another clinic voluntarily attending the resident clinic, the physician is aware of the resident’s skills and qualifications and knows that supervision is being provided by an attending physician, which allows informed consent to be made, as a study by Unruh et al³ shows. The patient’s autonomy allows them to choose their treating provider.

However, there are several reasons why the resident may be hesitant to enter the room. One concern may be that during a TBSE the provider usually examines the patient’s genitals, rectum, and breasts.⁴ Because the resident knows the individual personally, the patient and/or the provider may be uncomfortable checking these areas, leaving a portion of the examination unperformed. This neglect may harm the patient (eg, a genital melanoma is missed), violating the tenant of nonmaleficence.

The effect of the medical hierarchy also should be considered. The de facto hierarchy of attendings supervising residents, interns, and medical students, with each group having some oversight over the next, can have positive effects on education and appropriate patient management but also can prove to be detrimental to the patient and provider in some circumstances. Studies have shown that residents may be less willing to disagree with their superior’s opinions for fear of negative reactions and harmful effects on their future careers.^5-7 The hierarchy of medicine also can affect a resident’s moral judgement by intimidating the practitioner to perform tasks or make diagnoses they may not wish to make.^5,6,8,9 For example, the resident may send a prescription for a medication that the attending requested despite no clear indication of need. This mingling of patient and supervisor roles can result in a resident treating their attending physician inconsistently with their standard of care.

Navigating the Ethics of Treating Family Members

The American Medical Association Code of Medical Ethics Opinions on Patient-Physician Relationships highlights treating family members as an important ethical topic. Although most residents and attendings are not biologically related, a familial-style relationship exists in many dermatology programs between attendings and residents due to the close-knit nature of dermatology programs. Diagnostic and treatment accuracy may be diminished by the discomfort or disbelief that a condition could affect someone the resident cares about.¹⁰

The American Medical Association also states that a physician can treat family members in an emergency situation or for short-term minor problems. If these 2 exceptions were to be extrapolated to apply to situations involving residents and attendings in addition to family, there would be situations where a dermatology resident could ethically treat their attending physician.¹⁰ If the attending physician was worried about a problem that was deemed potentially life-threatening, such as a rapidly progressive bullous eruption concerning for Stevens-Johnson syndrome following the initiation of a new medication, and they wanted an urgent evaluation and biopsy, an ethicist could argue that urgent treatment is medically indicated as deferring treatment could have negative consequences on the patient’s health. In addition, if the attending found a splinter in their finger following yardwork and needed assistance in removal, this also could be treated by their resident, as it is minimally invasive and has a finite conclusion.

Treating Nonsupervisory Attendings

In the case of performing a TBSE on an attending from another specialty, it would be acceptable and less ethically ambiguous if no close personal relationship existed between the two practitioners, as this patient would have no direct oversight over the resident physician.

Final Thoughts

Each situation that residents face may carry ethical implications with perspectives from the patient, provider, and bystanders. The above scenarios highlight specific instances that a dermatology resident may face and provide insight into how they may approach the situations. At the same time, it is important to remember that every situation is different and requires a unique approach. Fortunately,physicians—specifically dermatologists—are provided many resources to help navigate challenging scenarios.

Acknowledgments—The author thanks Jane M. Grant-Kels, MD (Farmington, Connecticut), for reviewing this paper and providing feedback to improve its content, as well as Warren R. Heymann, MD (Camden, New Jersey), for assisting in the creation of this topic and article.

Residents are confronted daily with situations in clinic that require a foundation in medical ethics to assist in decision-making. Attending physicians require health care services and at times may seek care from resident physicians. If the attending physician has direct oversight over the resident, however, the ethics of the resident treating them need to be addressed. Although patients have autonomy to choose whoever they want as a physician, nonmaleficence dictates that the resident may forego treatment due to concerns for providing suboptimal care; however, this same attending may be treated under specific circumstances. This column explores the ethical implications of both situations.

The Ethical Dilemma of Treating an Attending

Imagine this scenario: You are in your resident general dermatology clinic seeing patients with an attending overseeing your clinical decisions following each encounter. You look on your schedule and see that the next patient is one of your pediatric dermatology attendings for a total-body skin examination (TBSE). You have never treated a physician that oversees you, and you ponder whether you should perform the examination or fetch your attending to perform the encounter alone.

This conundrum then brings other questions to mind: Would changing the reason for the appointment (ie, an acute problem vs a TBSE) alter your decision as to whether or not you would treat this attending? Would the situation be different if this was an attending in a different department?

Ethics Curriculum for Residents

Medical providers face ethical dilemmas daily, and dermatologists and dermatology residents are not excluded. Dermatoethics can provide a framework for the best approach to this hypothetical situation. To equip residents with resources on ethics and a cognitive framework to approach similar situations, the American Board of Dermatology has created an ethics curriculum for residents to learn over their 3 years of training.¹

One study that analyzed the ethical themes portrayed in essays by fourth-year medical students showed that the most common themes included autonomy, social justice, nonmaleficence, beneficence, honesty, and respect.² These themes must be considered in different permutations throughout ethical conundrums.

In the situation of an attending physician who supervises a resident in another clinic voluntarily attending the resident clinic, the physician is aware of the resident’s skills and qualifications and knows that supervision is being provided by an attending physician, which allows informed consent to be made, as a study by Unruh et al³ shows. The patient’s autonomy allows them to choose their treating provider.

However, there are several reasons why the resident may be hesitant to enter the room. One concern may be that during a TBSE the provider usually examines the patient’s genitals, rectum, and breasts.⁴ Because the resident knows the individual personally, the patient and/or the provider may be uncomfortable checking these areas, leaving a portion of the examination unperformed. This neglect may harm the patient (eg, a genital melanoma is missed), violating the tenant of nonmaleficence.

The effect of the medical hierarchy also should be considered. The de facto hierarchy of attendings supervising residents, interns, and medical students, with each group having some oversight over the next, can have positive effects on education and appropriate patient management but also can prove to be detrimental to the patient and provider in some circumstances. Studies have shown that residents may be less willing to disagree with their superior’s opinions for fear of negative reactions and harmful effects on their future careers.^5-7 The hierarchy of medicine also can affect a resident’s moral judgement by intimidating the practitioner to perform tasks or make diagnoses they may not wish to make.^5,6,8,9 For example, the resident may send a prescription for a medication that the attending requested despite no clear indication of need. This mingling of patient and supervisor roles can result in a resident treating their attending physician inconsistently with their standard of care.

Navigating the Ethics of Treating Family Members

The American Medical Association Code of Medical Ethics Opinions on Patient-Physician Relationships highlights treating family members as an important ethical topic. Although most residents and attendings are not biologically related, a familial-style relationship exists in many dermatology programs between attendings and residents due to the close-knit nature of dermatology programs. Diagnostic and treatment accuracy may be diminished by the discomfort or disbelief that a condition could affect someone the resident cares about.¹⁰

The American Medical Association also states that a physician can treat family members in an emergency situation or for short-term minor problems. If these 2 exceptions were to be extrapolated to apply to situations involving residents and attendings in addition to family, there would be situations where a dermatology resident could ethically treat their attending physician.¹⁰ If the attending physician was worried about a problem that was deemed potentially life-threatening, such as a rapidly progressive bullous eruption concerning for Stevens-Johnson syndrome following the initiation of a new medication, and they wanted an urgent evaluation and biopsy, an ethicist could argue that urgent treatment is medically indicated as deferring treatment could have negative consequences on the patient’s health. In addition, if the attending found a splinter in their finger following yardwork and needed assistance in removal, this also could be treated by their resident, as it is minimally invasive and has a finite conclusion.

Treating Nonsupervisory Attendings

In the case of performing a TBSE on an attending from another specialty, it would be acceptable and less ethically ambiguous if no close personal relationship existed between the two practitioners, as this patient would have no direct oversight over the resident physician.

Final Thoughts

Each situation that residents face may carry ethical implications with perspectives from the patient, provider, and bystanders. The above scenarios highlight specific instances that a dermatology resident may face and provide insight into how they may approach the situations. At the same time, it is important to remember that every situation is different and requires a unique approach. Fortunately,physicians—specifically dermatologists—are provided many resources to help navigate challenging scenarios.

Acknowledgments—The author thanks Jane M. Grant-Kels, MD (Farmington, Connecticut), for reviewing this paper and providing feedback to improve its content, as well as Warren R. Heymann, MD (Camden, New Jersey), for assisting in the creation of this topic and article.

The Diagnosis: Scleromyxedema

A punch biopsy of the upper back performed at an outside institution revealed increased histiocytes and abundant interstitial mucin confined to the papillary dermis (Figures 1 and 2), consistent with the lichen myxedematosus (LM) papules that may be seen in scleromyxedema. Serum protein electrophoresis revealed the presence of a protein of restricted mobility on the gamma region that occupied 5.3% of the total protein (0.3 g/dL). Urine protein electrophoresis showed free kappa light chain monoclonal protein in the gamma region. Immunofixation electrophoresis revealed the presence of IgG kappa monoclonal protein in the gamma region with 10% monotype kappa cells. The presence of Raynaud phenomenon and positive antinuclear antibody (1:320, speckled) was noted. Laboratory studies for thyroid-stimulating hormone, C-reactive protein, Scl-70 antibody, myositis panel, ribonucleoprotein antibody, Smith antibody, Sjögren syndrome–related antigens A and B antibodies, rheumatoid factor, and RNA polymerase III antibody all were within reference range. Our patient was treated with monthly intravenous immunoglobulin (IVIG), and he noted substantial improvement in skin findings after 3 months of IVIG.

Localized lichen myxedematosus is a rare idiopathic cutaneous disease that clinically is characterized by waxy indurated papules and histologically is characterized by diffuse mucin deposition and fibroblast proliferation in the upper dermis.¹ Scleromyxedema is a diffuse variant of LM in which the papules and plaques of LM are associated with skin thickening involving almost the entire body and associated systemic disease. The exact mechanism of this disease is unknown, but the most widely accepted hypothesis is that immunoglobulins and cytokines contribute to the synthesis of glycosaminoglycans and thereby the deposition of mucin in the dermis.² Scleromyxedema has a chronic course and generally responds poorly to existing treatments.¹ Partial improvement has been demonstrated in treatment with topical calcineurin inhibitors and topical steroids.²

The differential diagnosis in our patient included scleromyxedema, scleredema, scleroderma, LM, and reticular erythematosus mucinosis. He was diagnosed with scleromyxedema with kappa monoclonal gammopathy. Scleromyxedema is a rare disorder involving the deposition of mucinous material in the papillary dermis that causes the formation of infiltrative skin lesions.³ The etiology is unknown, but the presence of a monoclonal protein is an important characteristic of this disorder. It is important to rule out thyroid disease as a possible etiology before concluding that the disease process is driven by the monoclonal gammopathy; this will help determine appropriate therapies.^4,5 Usually the monoclonal protein is associated with the IgG lambda subtype. Intravenous immunoglobulin often is considered as a first-line treatment of scleromyxedema and usually is administered at a dosage of 2 g/kg divided over 2 to 5 consecutive days per month.³ Previously, our patient had been treated with IVIG for 3 years for chronic inflammatory demyelinating polyneuropathy and had stopped 1 to 2 years before his cutaneous symptoms started. Generally, scleromyxedema patients must stay on IVIG long-term to prevent relapse, typically every 6 to 8 weeks. Second-line treatments for scleromyxedema include systemic corticosteroids and thalidomide.⁶ Scleromyxedema and LM have several clinical and histopathologic features in common. Our patient’s biopsy revealed increased mucin deposition associated with fibroblast proliferation confined to the superficial dermis. These histologic changes can be seen in the setting of either LM or scleromyxedema. Our patient’s diffuse skin thickening and monoclonal gammopathy were more characteristic of scleromyxedema. In contrast, LM is a localized eruption with no internal organ manifestations and no associated systemic disease, such as monoclonal gammopathy and thyroid disease.

Scleredema adultorum of Buschke (also referred to as scleredema) is a rare idiopathic dermatologic condition characterized by thickening and tightening of the skin that leads to firm, nonpitting, woody edema that initially involves the upper back and neck but can spread to the face, scalp, and shoulders; importantly, scleredema spares the hands and feet.⁷ Scleredema has been associated with type 2 diabetes mellitus, streptococcal upper respiratory tract infections, and monoclonal gammopathy.⁸ Although our patient did have a monoclonal gammopathy, he also experienced prominent hand involvement with diffuse skin thickening, which is not typical of scleredema. Additionally, biopsy of scleredema would show increased mucin but would not show the proliferation of fibroblasts that was seen in our patient’s biopsy. Furthermore, scleredema has more profound diffuse superficial and deep mucin deposition compared to scleromyxedema. Scleroderma is an autoimmune cutaneous condition that is divided into 2 categories: localized scleroderma and systemic sclerosis (SSc).⁹ Localized scleroderma (also called morphea) often is characterized by indurated hyperpigmented or hypopigmented lesions. There is an absence of Raynaud phenomenon, telangiectasia, and systemic disease.⁹ Systemic sclerosis is further divided into 2 categories—limited cutaneous and diffuse cutaneous—which are differentiated by the extent of organ system involvement. Limited cutaneous SSc involves calcinosis, Raynaud phenomenon, esophageal dysmotility, skin sclerosis distal to the elbows and knees, and telangiectasia.⁹ Diffuse cutaneous SSc is characterized by Raynaud phenomenon; cutaneous sclerosis proximal to the elbows and knees; and fibrosis of the gastrointestinal, pulmonary, renal, and cardiac systems.9 Scl-70 antibodies are specific for diffuse cutaneous SSc, and centromere antibodies are specific for limited cutaneous SSc. Scleromyxedema shares many of the same clinical symptoms as scleroderma; therefore, histopathologic examination is important for differentiating these disorders. Histologically, scleroderma is characterized by thickened collagen bundles associated with a variable degree of perivascular and interstitial lymphoplasmacytic inflammation. No increased dermal mucin is present.⁹ Our patient did not have the clinical cutaneous features of localized scleroderma and lacked the signs of internal organ involvement that typically are found in SSc. He did have Raynaud phenomenon but did not have matlike telangiectases or Scl-70 or centromere antibodies.

Reticular erythematosus mucinosis (REM) is a rare inflammatory cutaneous disease that is characterized by diffuse reticular erythematous macules or papules that may be asymptomatic or associated with pruritus.¹⁰ Reticular erythematosus mucinosis most frequently affects middle-aged women and appears on the trunk.⁹ Our patient was not part of the demographic group most frequently affected by REM. More importantly, our patient’s lesions were not erythematous or reticular in appearance, making the diagnosis of REM unlikely. Furthermore, REM has no associated cutaneous sclerosis or induration.

The Diagnosis: Scleromyxedema

A punch biopsy of the upper back performed at an outside institution revealed increased histiocytes and abundant interstitial mucin confined to the papillary dermis (Figures 1 and 2), consistent with the lichen myxedematosus (LM) papules that may be seen in scleromyxedema. Serum protein electrophoresis revealed the presence of a protein of restricted mobility on the gamma region that occupied 5.3% of the total protein (0.3 g/dL). Urine protein electrophoresis showed free kappa light chain monoclonal protein in the gamma region. Immunofixation electrophoresis revealed the presence of IgG kappa monoclonal protein in the gamma region with 10% monotype kappa cells. The presence of Raynaud phenomenon and positive antinuclear antibody (1:320, speckled) was noted. Laboratory studies for thyroid-stimulating hormone, C-reactive protein, Scl-70 antibody, myositis panel, ribonucleoprotein antibody, Smith antibody, Sjögren syndrome–related antigens A and B antibodies, rheumatoid factor, and RNA polymerase III antibody all were within reference range. Our patient was treated with monthly intravenous immunoglobulin (IVIG), and he noted substantial improvement in skin findings after 3 months of IVIG.

Localized lichen myxedematosus is a rare idiopathic cutaneous disease that clinically is characterized by waxy indurated papules and histologically is characterized by diffuse mucin deposition and fibroblast proliferation in the upper dermis.¹ Scleromyxedema is a diffuse variant of LM in which the papules and plaques of LM are associated with skin thickening involving almost the entire body and associated systemic disease. The exact mechanism of this disease is unknown, but the most widely accepted hypothesis is that immunoglobulins and cytokines contribute to the synthesis of glycosaminoglycans and thereby the deposition of mucin in the dermis.² Scleromyxedema has a chronic course and generally responds poorly to existing treatments.¹ Partial improvement has been demonstrated in treatment with topical calcineurin inhibitors and topical steroids.²

The differential diagnosis in our patient included scleromyxedema, scleredema, scleroderma, LM, and reticular erythematosus mucinosis. He was diagnosed with scleromyxedema with kappa monoclonal gammopathy. Scleromyxedema is a rare disorder involving the deposition of mucinous material in the papillary dermis that causes the formation of infiltrative skin lesions.³ The etiology is unknown, but the presence of a monoclonal protein is an important characteristic of this disorder. It is important to rule out thyroid disease as a possible etiology before concluding that the disease process is driven by the monoclonal gammopathy; this will help determine appropriate therapies.^4,5 Usually the monoclonal protein is associated with the IgG lambda subtype. Intravenous immunoglobulin often is considered as a first-line treatment of scleromyxedema and usually is administered at a dosage of 2 g/kg divided over 2 to 5 consecutive days per month.³ Previously, our patient had been treated with IVIG for 3 years for chronic inflammatory demyelinating polyneuropathy and had stopped 1 to 2 years before his cutaneous symptoms started. Generally, scleromyxedema patients must stay on IVIG long-term to prevent relapse, typically every 6 to 8 weeks. Second-line treatments for scleromyxedema include systemic corticosteroids and thalidomide.⁶ Scleromyxedema and LM have several clinical and histopathologic features in common. Our patient’s biopsy revealed increased mucin deposition associated with fibroblast proliferation confined to the superficial dermis. These histologic changes can be seen in the setting of either LM or scleromyxedema. Our patient’s diffuse skin thickening and monoclonal gammopathy were more characteristic of scleromyxedema. In contrast, LM is a localized eruption with no internal organ manifestations and no associated systemic disease, such as monoclonal gammopathy and thyroid disease.

Scleredema adultorum of Buschke (also referred to as scleredema) is a rare idiopathic dermatologic condition characterized by thickening and tightening of the skin that leads to firm, nonpitting, woody edema that initially involves the upper back and neck but can spread to the face, scalp, and shoulders; importantly, scleredema spares the hands and feet.⁷ Scleredema has been associated with type 2 diabetes mellitus, streptococcal upper respiratory tract infections, and monoclonal gammopathy.⁸ Although our patient did have a monoclonal gammopathy, he also experienced prominent hand involvement with diffuse skin thickening, which is not typical of scleredema. Additionally, biopsy of scleredema would show increased mucin but would not show the proliferation of fibroblasts that was seen in our patient’s biopsy. Furthermore, scleredema has more profound diffuse superficial and deep mucin deposition compared to scleromyxedema. Scleroderma is an autoimmune cutaneous condition that is divided into 2 categories: localized scleroderma and systemic sclerosis (SSc).⁹ Localized scleroderma (also called morphea) often is characterized by indurated hyperpigmented or hypopigmented lesions. There is an absence of Raynaud phenomenon, telangiectasia, and systemic disease.⁹ Systemic sclerosis is further divided into 2 categories—limited cutaneous and diffuse cutaneous—which are differentiated by the extent of organ system involvement. Limited cutaneous SSc involves calcinosis, Raynaud phenomenon, esophageal dysmotility, skin sclerosis distal to the elbows and knees, and telangiectasia.⁹ Diffuse cutaneous SSc is characterized by Raynaud phenomenon; cutaneous sclerosis proximal to the elbows and knees; and fibrosis of the gastrointestinal, pulmonary, renal, and cardiac systems.9 Scl-70 antibodies are specific for diffuse cutaneous SSc, and centromere antibodies are specific for limited cutaneous SSc. Scleromyxedema shares many of the same clinical symptoms as scleroderma; therefore, histopathologic examination is important for differentiating these disorders. Histologically, scleroderma is characterized by thickened collagen bundles associated with a variable degree of perivascular and interstitial lymphoplasmacytic inflammation. No increased dermal mucin is present.⁹ Our patient did not have the clinical cutaneous features of localized scleroderma and lacked the signs of internal organ involvement that typically are found in SSc. He did have Raynaud phenomenon but did not have matlike telangiectases or Scl-70 or centromere antibodies.

Reticular erythematosus mucinosis (REM) is a rare inflammatory cutaneous disease that is characterized by diffuse reticular erythematous macules or papules that may be asymptomatic or associated with pruritus.¹⁰ Reticular erythematosus mucinosis most frequently affects middle-aged women and appears on the trunk.⁹ Our patient was not part of the demographic group most frequently affected by REM. More importantly, our patient’s lesions were not erythematous or reticular in appearance, making the diagnosis of REM unlikely. Furthermore, REM has no associated cutaneous sclerosis or induration.

The Diagnosis: Scleromyxedema

A punch biopsy of the upper back performed at an outside institution revealed increased histiocytes and abundant interstitial mucin confined to the papillary dermis (Figures 1 and 2), consistent with the lichen myxedematosus (LM) papules that may be seen in scleromyxedema. Serum protein electrophoresis revealed the presence of a protein of restricted mobility on the gamma region that occupied 5.3% of the total protein (0.3 g/dL). Urine protein electrophoresis showed free kappa light chain monoclonal protein in the gamma region. Immunofixation electrophoresis revealed the presence of IgG kappa monoclonal protein in the gamma region with 10% monotype kappa cells. The presence of Raynaud phenomenon and positive antinuclear antibody (1:320, speckled) was noted. Laboratory studies for thyroid-stimulating hormone, C-reactive protein, Scl-70 antibody, myositis panel, ribonucleoprotein antibody, Smith antibody, Sjögren syndrome–related antigens A and B antibodies, rheumatoid factor, and RNA polymerase III antibody all were within reference range. Our patient was treated with monthly intravenous immunoglobulin (IVIG), and he noted substantial improvement in skin findings after 3 months of IVIG.

Localized lichen myxedematosus is a rare idiopathic cutaneous disease that clinically is characterized by waxy indurated papules and histologically is characterized by diffuse mucin deposition and fibroblast proliferation in the upper dermis.¹ Scleromyxedema is a diffuse variant of LM in which the papules and plaques of LM are associated with skin thickening involving almost the entire body and associated systemic disease. The exact mechanism of this disease is unknown, but the most widely accepted hypothesis is that immunoglobulins and cytokines contribute to the synthesis of glycosaminoglycans and thereby the deposition of mucin in the dermis.² Scleromyxedema has a chronic course and generally responds poorly to existing treatments.¹ Partial improvement has been demonstrated in treatment with topical calcineurin inhibitors and topical steroids.²

The differential diagnosis in our patient included scleromyxedema, scleredema, scleroderma, LM, and reticular erythematosus mucinosis. He was diagnosed with scleromyxedema with kappa monoclonal gammopathy. Scleromyxedema is a rare disorder involving the deposition of mucinous material in the papillary dermis that causes the formation of infiltrative skin lesions.³ The etiology is unknown, but the presence of a monoclonal protein is an important characteristic of this disorder. It is important to rule out thyroid disease as a possible etiology before concluding that the disease process is driven by the monoclonal gammopathy; this will help determine appropriate therapies.^4,5 Usually the monoclonal protein is associated with the IgG lambda subtype. Intravenous immunoglobulin often is considered as a first-line treatment of scleromyxedema and usually is administered at a dosage of 2 g/kg divided over 2 to 5 consecutive days per month.³ Previously, our patient had been treated with IVIG for 3 years for chronic inflammatory demyelinating polyneuropathy and had stopped 1 to 2 years before his cutaneous symptoms started. Generally, scleromyxedema patients must stay on IVIG long-term to prevent relapse, typically every 6 to 8 weeks. Second-line treatments for scleromyxedema include systemic corticosteroids and thalidomide.⁶ Scleromyxedema and LM have several clinical and histopathologic features in common. Our patient’s biopsy revealed increased mucin deposition associated with fibroblast proliferation confined to the superficial dermis. These histologic changes can be seen in the setting of either LM or scleromyxedema. Our patient’s diffuse skin thickening and monoclonal gammopathy were more characteristic of scleromyxedema. In contrast, LM is a localized eruption with no internal organ manifestations and no associated systemic disease, such as monoclonal gammopathy and thyroid disease.

Scleredema adultorum of Buschke (also referred to as scleredema) is a rare idiopathic dermatologic condition characterized by thickening and tightening of the skin that leads to firm, nonpitting, woody edema that initially involves the upper back and neck but can spread to the face, scalp, and shoulders; importantly, scleredema spares the hands and feet.⁷ Scleredema has been associated with type 2 diabetes mellitus, streptococcal upper respiratory tract infections, and monoclonal gammopathy.⁸ Although our patient did have a monoclonal gammopathy, he also experienced prominent hand involvement with diffuse skin thickening, which is not typical of scleredema. Additionally, biopsy of scleredema would show increased mucin but would not show the proliferation of fibroblasts that was seen in our patient’s biopsy. Furthermore, scleredema has more profound diffuse superficial and deep mucin deposition compared to scleromyxedema. Scleroderma is an autoimmune cutaneous condition that is divided into 2 categories: localized scleroderma and systemic sclerosis (SSc).⁹ Localized scleroderma (also called morphea) often is characterized by indurated hyperpigmented or hypopigmented lesions. There is an absence of Raynaud phenomenon, telangiectasia, and systemic disease.⁹ Systemic sclerosis is further divided into 2 categories—limited cutaneous and diffuse cutaneous—which are differentiated by the extent of organ system involvement. Limited cutaneous SSc involves calcinosis, Raynaud phenomenon, esophageal dysmotility, skin sclerosis distal to the elbows and knees, and telangiectasia.⁹ Diffuse cutaneous SSc is characterized by Raynaud phenomenon; cutaneous sclerosis proximal to the elbows and knees; and fibrosis of the gastrointestinal, pulmonary, renal, and cardiac systems.9 Scl-70 antibodies are specific for diffuse cutaneous SSc, and centromere antibodies are specific for limited cutaneous SSc. Scleromyxedema shares many of the same clinical symptoms as scleroderma; therefore, histopathologic examination is important for differentiating these disorders. Histologically, scleroderma is characterized by thickened collagen bundles associated with a variable degree of perivascular and interstitial lymphoplasmacytic inflammation. No increased dermal mucin is present.⁹ Our patient did not have the clinical cutaneous features of localized scleroderma and lacked the signs of internal organ involvement that typically are found in SSc. He did have Raynaud phenomenon but did not have matlike telangiectases or Scl-70 or centromere antibodies.

Reticular erythematosus mucinosis (REM) is a rare inflammatory cutaneous disease that is characterized by diffuse reticular erythematous macules or papules that may be asymptomatic or associated with pruritus.¹⁰ Reticular erythematosus mucinosis most frequently affects middle-aged women and appears on the trunk.⁹ Our patient was not part of the demographic group most frequently affected by REM. More importantly, our patient’s lesions were not erythematous or reticular in appearance, making the diagnosis of REM unlikely. Furthermore, REM has no associated cutaneous sclerosis or induration.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare nodular unencapsulated mass that is characterized by benign anomalous vascular hyperplasia of epithelioidlike endothelial cells attached to dilated blood vessels. The mass is surrounded by lymphocytes and eosinophils that can present clinically as papules, plaques, or nodules.¹ The etiology of ALHE is unknown; it is hypothesized that it is a vascular neoplasm or a lymphoproliferative disorder.

Coccidioidomycosis (CM) is a prevalent deep fungal infection endemic to the southwestern United States caused by Coccidioides immitis and Coccidioides posadasii. Infection can occur from direct inoculation through abrasions or direct trauma but usually occurs through the inhalation of spores and can result in a reactive rash (eg, Sweet syndrome, erythema nodosum, interstitial granulomatous dermatitis).² Coccidioidomycosis also can result in respiratory pneumonia and dissemination from pulmonary infection of the skin. As such, it is important to distinguish CM and its immunologically mediated eruptions for accurate diagnosis and treatment.

We report a novel case of ALHE as a reactive dermatologic presentation in a patient with CM.

Case Report

A 72-year-old woman presented to the dermatology clinic with itchy papules and plaques on the arms and legs of 17 years’ duration. Her medical history included coronary artery disease and hypercholesterolemia as well as a remote history of cutaneous marginal zone B-cell lymphoma of the nose, which was confirmed by histology and treated more than 10 years prior and has remained in remission for 6 years. Her current medications included aspirin, atorvastatin, lisinopril, and metoprolol succinate.

Our patient first presented to our dermatology clinic for itchy nodules and papules on the legs and arms. The patient previously had been seen by another dermatologist 2 months prior for the same condition. At that time, biopsies of the lesions were reported as prurigo nodules. Physical examination at the current presentation revealed round, pink to flesh-colored, raised papules and plaques scattered on the arms and legs (Figure 1). The differential diagnosis included lymphomatoid papulosis, cutaneous B-cell lymphoma, pseudolymphoma, cutaneous CM, and papular mucinosis.

Four-mm punch biopsies of the right proximal pretibial region and left knee region were taken and sent for histologic analysis, direct immunofluorescence testing, and tissue culture. Testing for atypical mycobacteria and deep fungal infection was negative; bacterial cultures and sensitivity testing were negative. Direct immunofluorescence testing was negative. Microscopic examination of material from the right proximal pretibial region showed widely dilated, variously shaped, large blood vessels in a multinodular pattern; the vessels also were surrounded by an inflammatory cell infiltrate containing eosinophils. Histologic findings were consistent with ALHE.

Subsequent biopsies were completed 2 weeks and 1 month from the initial presentation. Both histology reports—from 2 different histopathology laboratories—were consistent with ALHE (Figure 2). Additional work-up during the patient’s initial visit to our clinic for the rash included CM serologic testing, which demonstrated IgM and IgG antibodies. Subsequently, chest radiography revealed a 2.2×2.3-cm mass in the right lower lobe of the lung. Follow-up computed tomography 1 month later confirmed the nodule in the same area to be 2.3×2.1×1.8 cm.

The patient was referred to pulmonology and was treated for pulmonary CM with oral fluconazole 200 mg twice daily for 4 months. Initial treatment also included clobetasol cream 0.05% applied twice daily, which did not produce marked improvement in pruritus. Narrowband UVB phototherapy was attempted, but the patient could not complete the course because of travel time to the office; however, the patient’s ALHE improved considerably with the fluconazole treatment for pulmonary CM.

Oral doxycycline 100 mg twice daily was added to the fluconazole 2 months after her initial visit to our office, which kept the ALHE at bay and helped with the pruritus (Figure 3). Pulmonology and primary care comanaged the pulmonary CM with oral fluconazole 200 mg twice daily. Repeat serologic testing for CM was negative for IgG and IgM after 14 months since the initial visit to the office.

Comment

Pulmonary CM infection has varying dermatologic manifestations. A PubMed search of articles indexed for MEDLINE using the terms ALHE and coccidioidomycosis yielded no case reports; in fact, there have been few reported cases of ALHE at all. Notable conditions associated with ALHE include membranous nephropathy and arteriovenous malformations treated with corticosteroids and surgery, respectively.^3,4 Our case is a rare presentation of CM infection manifesting with ALHE. Following treatment and remission for our patient’s CM infection, the ALHE lesion decreased in size.

Standard treatment of uncomplicated CM involves azole antifungals, typically oral fluconazole or itraconazole 400 to 600 mg/d. In more severe cases (eg, immunocompromised patients) amphotericin B can be used.⁵ Our patient was treated with oral fluconazole 200 mg twice daily for 4 months.

In the literature, treatment via surgical excision, steroid injection, pulsed-dye laser therapy, and radiotherapy also has been described.^6-8 Antibiotics including clindamycin, doxycycline, and amoxicillin-clavulanate also have been shown to be effective.⁹

In our patient, ALHE improved when oral doxycycline 100 mg twice daily was added to the oral fluconazole. In fact, after 4 months of treatment, the CM infection and ALHE lesions both improved to a point at which the lesions were not visible. When those lesions recurred 15 months later, they responded with another course of doxycycline and fluconazole.

Upon recurrence, the patient was asked to have her care transferred to her pulmonologist, who then managed the fluconazole regimen. During the pulmonologist’s workup, no peripheral eosinophilia was found. This is important because eosinophils can be a marker for CM infection; in this case, however, the ALHE lesion was a reactive process to the infection. Classically known to play a reactive role in fungal infection, these white blood cells demonstrate reactivity to the environmental fungus Alternaria alternata by contact-dependent killing, utilizing β2 integrins and CD11b to recognize and adhere to β-glucan. Eosinophils react through contact-dependent killing, releasing cytotoxic granule proteins and proinflammatory mediators, and have been documented to occur in CM and Paracoccidioides brasiliensis infection, in which they deposit major basic protein on the organism.¹⁰ Most pertinent to our case with ALHE and CM is the ability of eosinophils to communicate with other immune cells. Eosinophils play a role in the active inflammation of CM through cytokine signaling, which may propagate formation of ALHE.

The function of eosinophils in ALHE is poorly understood; it is unclear whether they act as a primary driver of pathogenesis or are simply indicators of secondary infiltration or infection. Our review of the current literature suggests that eosinophils are unnecessary for progression of ALHE but might be involved at its onset. As reported, even monoclonal antibody therapy (eg, mepolizumab and benralizumab) that effectively depletes eosinophil levels by negating IL-5 signaling do not slow progression of ALHE.¹¹ Symptomatic changes are modest at best (ie, simply softening the ALHE nodules).

Our patient had no peripheral eosinophilia, suggesting that the onset of ALHE might not be caused by eosinophilia but a different inflammatory process—in this patient, by CM. Because peripheral eosinophilia was not seen in our patient, the presence of eosinophils in the ALHE lesion likely is unnecessary for its onset or progression but is a secondary process that exacerbates the lesion. The pathogenesis is unknown but could be directed toward lymphocytes and plasma cells, with eosinophils as part of the dynamic process.¹¹

Conclusion

Because reports of an association between CM and ALHE are limited, our case is distinguished by a unique clinical presentation of ALHE. When a patient is given a diagnosis of ALHE, it therefore is important to consider exposure to CM as a cause, especially in patients who reside in or travel to a region where CM is endemic.

PORTLAND, ORE. – In his nearly 2 decades of dermatology practice, Keith L. Duffy, MD, has seen his share of cases where Mohs surgery was misused or misappropriated.

“Appropriate use criteria in Mohs are near and dear to my heart,” Dr. Duffy, associate professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “I want to protect our specialty. I see patients who have dozens of skin cancers. I want to emphasize the long game of management in those patients. You have to think about the tumors in terms of decades.”

In 2012, an ad hoc task force from the American Academy of Dermatology (AAD), the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery developed appropriate use criteria (AUC) for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered. The task force used a 9-point scale to rate each indication, as follows:

• A score of 7 to 9: The use of MMS is appropriate for the specific indication and is generally considered acceptable.
• A score of 4 to 6: The use of MMS is uncertain for the specific indication, although its use may be appropriate and acceptable.
• A score of 1 to 3: The use of MMS is inappropriate for the specific indication and is generally not considered acceptable.

These ratings were translated into a free Mohs Surgery Appropriate Use Criteria App developed by the AAD.

Subsequently, Dr. Duffy and colleagues retrospectively examined the University of Utah’s adherence to the Mohs AUC over the course of 3 months. Their analysis, published in 2015, included 1,026 nonmelanoma skin cancers in 724 patients. Of the 1,026 cancers, 350 (34.1%) were treated with MMS. Of these, 339 (96.9%) were deemed appropriate based on the AUC guidelines, 4 (1.1%) were deemed uncertain, and 7 (2%) were deemed inappropriate.

There were also 611 skin cancers that were not treated with Mohs but met criteria for treatment with Mohs. “Most of these were AUC 7 tumors,” Dr. Duffy said. “When I see an AUC 7 tumor, I give high consideration for certain anatomic locations, especially the lower leg, scalp, eyelid, genitalia, ear, hands, and feet. I also think about the patient’s age, the number of skin cancers, and histological characteristics. Consider the long game in management and remember that skin cancer patients can make a near infinite amount of skin cancers, so be conservative when excising skin cancers to preserve precious skin.”

In his opinion, full thickness wounds requiring sutures should be avoided on the scalp and lower leg, if possible. “Most carcinomas in these locations are superficial and not aggressive in immunocompetent patients,” said Dr. Duffy, who said he has had one patient in 12 years who was not a transplant patient who had a metastatic squamous cell carcinoma on the lower leg. “Postop complications can be totally avoided. I don’t worry about these patients bleeding or [about] dehiscence. They can go back and play golf the next day, so you save valuable skin where the real estate is precious. This underscores a practice pearl: Incorporate the Mohs AUC and consideration of anatomic location when considering the most appropriate treatment of skin cancers.”

He also advises dermatologists to consider the histopathologic characteristics of the tumor when treating skin cancers to reduce complications and save tissue, so that patients can resume their lifestyle. “When you read the pathology report, really think about what the dermatopathologist saw under the microscope,” said Dr. Duffy, who is an investigator at the University of Utah’s Huntsman Cancer Institute. He said that he is able to review the slides for 90% of his own cases before surgery. “I’m lucky that way, but if you have any questions, your dermatopathologist should be on speed dial.”

Ultimately, he concluded, proper selection of a treatment modality for a specific tumor and patient rules the day. “Tumors should be thought about in the context of the patient and not as a single or isolated cancer,” he said.

Dr. Duffy reported having no relevant disclosures.

PORTLAND, ORE. – In his nearly 2 decades of dermatology practice, Keith L. Duffy, MD, has seen his share of cases where Mohs surgery was misused or misappropriated.

“Appropriate use criteria in Mohs are near and dear to my heart,” Dr. Duffy, associate professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “I want to protect our specialty. I see patients who have dozens of skin cancers. I want to emphasize the long game of management in those patients. You have to think about the tumors in terms of decades.”

In 2012, an ad hoc task force from the American Academy of Dermatology (AAD), the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery developed appropriate use criteria (AUC) for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered. The task force used a 9-point scale to rate each indication, as follows:

• A score of 7 to 9: The use of MMS is appropriate for the specific indication and is generally considered acceptable.
• A score of 4 to 6: The use of MMS is uncertain for the specific indication, although its use may be appropriate and acceptable.
• A score of 1 to 3: The use of MMS is inappropriate for the specific indication and is generally not considered acceptable.

These ratings were translated into a free Mohs Surgery Appropriate Use Criteria App developed by the AAD.

Subsequently, Dr. Duffy and colleagues retrospectively examined the University of Utah’s adherence to the Mohs AUC over the course of 3 months. Their analysis, published in 2015, included 1,026 nonmelanoma skin cancers in 724 patients. Of the 1,026 cancers, 350 (34.1%) were treated with MMS. Of these, 339 (96.9%) were deemed appropriate based on the AUC guidelines, 4 (1.1%) were deemed uncertain, and 7 (2%) were deemed inappropriate.

There were also 611 skin cancers that were not treated with Mohs but met criteria for treatment with Mohs. “Most of these were AUC 7 tumors,” Dr. Duffy said. “When I see an AUC 7 tumor, I give high consideration for certain anatomic locations, especially the lower leg, scalp, eyelid, genitalia, ear, hands, and feet. I also think about the patient’s age, the number of skin cancers, and histological characteristics. Consider the long game in management and remember that skin cancer patients can make a near infinite amount of skin cancers, so be conservative when excising skin cancers to preserve precious skin.”

In his opinion, full thickness wounds requiring sutures should be avoided on the scalp and lower leg, if possible. “Most carcinomas in these locations are superficial and not aggressive in immunocompetent patients,” said Dr. Duffy, who said he has had one patient in 12 years who was not a transplant patient who had a metastatic squamous cell carcinoma on the lower leg. “Postop complications can be totally avoided. I don’t worry about these patients bleeding or [about] dehiscence. They can go back and play golf the next day, so you save valuable skin where the real estate is precious. This underscores a practice pearl: Incorporate the Mohs AUC and consideration of anatomic location when considering the most appropriate treatment of skin cancers.”

He also advises dermatologists to consider the histopathologic characteristics of the tumor when treating skin cancers to reduce complications and save tissue, so that patients can resume their lifestyle. “When you read the pathology report, really think about what the dermatopathologist saw under the microscope,” said Dr. Duffy, who is an investigator at the University of Utah’s Huntsman Cancer Institute. He said that he is able to review the slides for 90% of his own cases before surgery. “I’m lucky that way, but if you have any questions, your dermatopathologist should be on speed dial.”

Ultimately, he concluded, proper selection of a treatment modality for a specific tumor and patient rules the day. “Tumors should be thought about in the context of the patient and not as a single or isolated cancer,” he said.

Dr. Duffy reported having no relevant disclosures.

PORTLAND, ORE. – In his nearly 2 decades of dermatology practice, Keith L. Duffy, MD, has seen his share of cases where Mohs surgery was misused or misappropriated.

“Appropriate use criteria in Mohs are near and dear to my heart,” Dr. Duffy, associate professor of dermatology at the University of Utah, Salt Lake City, said at the annual meeting of the Pacific Dermatologic Association. “I want to protect our specialty. I see patients who have dozens of skin cancers. I want to emphasize the long game of management in those patients. You have to think about the tumors in terms of decades.”

In 2012, an ad hoc task force from the American Academy of Dermatology (AAD), the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery developed appropriate use criteria (AUC) for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered. The task force used a 9-point scale to rate each indication, as follows:

• A score of 7 to 9: The use of MMS is appropriate for the specific indication and is generally considered acceptable.
• A score of 4 to 6: The use of MMS is uncertain for the specific indication, although its use may be appropriate and acceptable.
• A score of 1 to 3: The use of MMS is inappropriate for the specific indication and is generally not considered acceptable.

These ratings were translated into a free Mohs Surgery Appropriate Use Criteria App developed by the AAD.

Subsequently, Dr. Duffy and colleagues retrospectively examined the University of Utah’s adherence to the Mohs AUC over the course of 3 months. Their analysis, published in 2015, included 1,026 nonmelanoma skin cancers in 724 patients. Of the 1,026 cancers, 350 (34.1%) were treated with MMS. Of these, 339 (96.9%) were deemed appropriate based on the AUC guidelines, 4 (1.1%) were deemed uncertain, and 7 (2%) were deemed inappropriate.

There were also 611 skin cancers that were not treated with Mohs but met criteria for treatment with Mohs. “Most of these were AUC 7 tumors,” Dr. Duffy said. “When I see an AUC 7 tumor, I give high consideration for certain anatomic locations, especially the lower leg, scalp, eyelid, genitalia, ear, hands, and feet. I also think about the patient’s age, the number of skin cancers, and histological characteristics. Consider the long game in management and remember that skin cancer patients can make a near infinite amount of skin cancers, so be conservative when excising skin cancers to preserve precious skin.”

In his opinion, full thickness wounds requiring sutures should be avoided on the scalp and lower leg, if possible. “Most carcinomas in these locations are superficial and not aggressive in immunocompetent patients,” said Dr. Duffy, who said he has had one patient in 12 years who was not a transplant patient who had a metastatic squamous cell carcinoma on the lower leg. “Postop complications can be totally avoided. I don’t worry about these patients bleeding or [about] dehiscence. They can go back and play golf the next day, so you save valuable skin where the real estate is precious. This underscores a practice pearl: Incorporate the Mohs AUC and consideration of anatomic location when considering the most appropriate treatment of skin cancers.”

He also advises dermatologists to consider the histopathologic characteristics of the tumor when treating skin cancers to reduce complications and save tissue, so that patients can resume their lifestyle. “When you read the pathology report, really think about what the dermatopathologist saw under the microscope,” said Dr. Duffy, who is an investigator at the University of Utah’s Huntsman Cancer Institute. He said that he is able to review the slides for 90% of his own cases before surgery. “I’m lucky that way, but if you have any questions, your dermatopathologist should be on speed dial.”

Ultimately, he concluded, proper selection of a treatment modality for a specific tumor and patient rules the day. “Tumors should be thought about in the context of the patient and not as a single or isolated cancer,” he said.

Dr. Duffy reported having no relevant disclosures.