MDedge Dermatology

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Children with concomitant atopic dermatitis (AD) and alopecia areata (AA) who were treated with dupilumab demonstrated significant hair regrowth over a mean of nearly 68 weeks, preliminary results from a small case series showed.

“We might be opening a new avenue for a safe, long-term treatment for our children with AA,” the study’s lead investigator, Emma Guttman-Yassky, MD, PhD, professor and chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York City, said in an interview during the annual meeting of the Society for Investigative Dermatology (SID), where the results were presented during a poster session. “I think AA is likely joining the atopic march, which may allow us to adapt some treatments from the atopy world to AA.”

When the original phase 2 and phase 3 trials of dupilumab for patients with moderate to severe AD were being conducted, Dr. Guttman-Yassky, one of the investigators, recalled observing that some patients who also had patch alopecia experienced hair regrowth. “I was scratching my head because, at the time, AA was considered to be only a Th1-driven disease,” she said. “I asked myself, ‘How can this happen?’ I looked in the literature and found many publications linking atopy in general to alopecia areata. The largest of the dermatologic publications showed that eczema and atopy in general are the highest comorbidities in alopecia areata.”

Courtesy Mount Sinai Health System

“This and other findings such as IL [interleukin]-13 genetic linkage with AA and high IgE in patients with AA link AA with Th2 immune skewing, particularly in the setting of atopy,” she continued. In addition, she said, in a large biomarker study involving the scalp and blood of patients with AA, “we found increases in Th2 biomarkers that were associated with alopecia severity.”
 

Case Series of 20 Pediatric Patients

As part of a case series of children with both AD and AA, Dr. Guttman-Yassky and colleagues evaluated hair regrowth using the Severity of Alopecia Tool (SALT) in 20 pediatric patients (mean age, 10.8 years) who were being treated at Mount Sinai. They collected patient demographics, atopic history, immunoglobulin E (IgE) levels, and SALT scores at follow-up visits every 12-16 weeks for more than 72 weeks and performed Spearman correlations between clinical scores, demographics, and IgE levels.

At baseline, the mean SALT score was 54.4, the mean IgE level was 1567.7 IU/mL, and 75% of patients also had a family history of atopy. The mean follow-up was 67.6 weeks. The researchers observed a significant reduction in SALT scores at week 48 compared with baseline (a mean score of 20.4; P < .01) and continued improvement up to at least 72 weeks (P < .01 vs baseline). They also noted that patients who achieved a treatment response at week 24 had baseline IgE levels > 200 IU/mL.

In other findings, baseline IgE positively correlated with improvement in SALT scores at week 36 (P < .05), while baseline SALT scores positively correlated with disease duration (P < .01) and negatively correlated with improvement in SALT scores at weeks 24, 36, and 48 (P < .005). “The robustness of the response surprised me,” Dr. Guttman-Yassky said in the interview. “Dupilumab for AA takes time to work, but once it kicks in, it kicks in. It takes anywhere from 6 to 12 months to see hair regrowth.”

She acknowledged certain limitations of the analysis, including its small sample size and the fact that it was not a standardized trial. “But, based on our data and the adult data, we are very encouraged about the potential of using dupilumab for children with AA,” she said.

Mount Sinai recently announced that the National Institutes of Health awarded a $6.6 million, 5-year grant to Dr. Guttman-Yassky to further investigate dupilumab as a treatment for children with AA. She will lead a multicenter controlled trial of 76 children with alopecia affecting at least 30% of the scalp, who will be randomized 2:1 (dupilumab:placebo) for 48 weeks, followed by 48 weeks of open-label dupilumab for all participants, with 16 weeks of follow-up, for a total of 112 weeks. Participating sites include Mount Sinai, Yale University, Northwestern University, and the University of California, Irvine.

Dr. Guttman-Yassky disclosed that she is a consultant to many pharmaceutical companies, including dupilumab manufacturers Sanofi and Regeneron.

A version of this article appeared on Medscape.com.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Between 2011 and 2019, chronic cutaneous wounds accounted for about one third of all health care visits for cutaneous wounds, and the most common diagnoses were open wounds of the thumb without nail damage. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.

Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”

A version of this article appeared on Medscape.com .

Between 2011 and 2019, chronic cutaneous wounds accounted for about one third of all health care visits for cutaneous wounds, and the most common diagnoses were open wounds of the thumb without nail damage. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.

Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”

A version of this article appeared on Medscape.com .

Between 2011 and 2019, chronic cutaneous wounds accounted for about one third of all health care visits for cutaneous wounds, and the most common diagnoses were open wounds of the thumb without nail damage. However, fewer than 8% of chronic wounds were managed by dermatologists during this time.

Those are among key findings from an analysis of National Ambulatory Medical Care Survey (NAMCS) data between 2011 and 2019 presented as a late-breaking abstract at the annual meeting of the Society for Investigative Dermatology. “Cutaneous wounds were estimated to account for 28.1 to 96.1 billion dollars in US health care costs in 2014,” one of the study authors, Rithi Chandy, MD, MS, a research fellow at the Center for Dermatology Research at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in an interview following the meeting. “By examining national trends in patient visits and treatment, we may be able to better inform health care utilization for cutaneous wounds.”

A version of this article appeared on Medscape.com .

Maternal in utero exposure to antibiotics was associated with an increased risk for infantile seborrheic dermatitis (SD) regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD.

The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.

SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”

“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”

She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.

Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.

A version of this article appeared on Medscape.com .

Maternal in utero exposure to antibiotics was associated with an increased risk for infantile seborrheic dermatitis (SD) regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD.

The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.

SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”

“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”

She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.

Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.

A version of this article appeared on Medscape.com .

Maternal in utero exposure to antibiotics was associated with an increased risk for infantile seborrheic dermatitis (SD) regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD.

The findings come from a large analysis of data from the United Kingdom that was presented during a late-breaking abstract session at the annual meeting of the Society for Investigative Dermatology.

SD is a common skin disease “that shares similarities with atopic dermatitis or atopic eczema as both are prevalent inflammatory skin diseases that can present with a chronic relapsing, remitting course,” the study’s corresponding author Zelma C. Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, said in an interview. “Like atopic dermatitis, the pathophysiology of seborrheic dermatitis is thought to be complex and involves an interplay between genetics, immune dysregulation, and alterations in lipid composition and the skin microbiome, among others.”

“We observed that antibiotic exposure in utero was primarily associated with an increased risk of infantile SD regardless of the mother’s history of SD, but this association was not as strong for childhood-onset SD,” Dr. Chiesa Fuxench said. “This would suggest that in utero exposure to antibiotics, particularly penicillin, may have its greatest effect on the colonization of skin microbiota in the newborn period leading to the development of infantile SD. Aside from seeking to improve our understanding of the pathophysiology of SD, our findings also suggest that infantile SD and childhood-onset SD may be separate entities with different risk factors, a hypothesis that needs to be further studied.”

She acknowledged certain limitations of the analysis, including the potential for unrecorded diagnoses of SD or misclassified cases in the database. For example, AD and psoriasis “may appear clinically like SD,” she said, although they performed sensitivity analysis excluding patients with these diagnoses and found similar results. In addition, there is the possibility that not all antibiotic exposures were captured in this database, and data on antibiotic exposure may be missing, she added.

Dr. Chiesa Fuxench disclosed that she received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, Vanda, and Incyte for work related to AD and from Menlo Therapeutics and Galderma for work related to prurigo nodularis. She has served as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection.

A version of this article appeared on Medscape.com .

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

TOPLINE:

Investigators found that the use of oral contraceptives (OCs) may be associated with an increased risk for frontal fibrosing alopecia (FFA) in women with a common variant in the CYP1B1 gene.

METHODOLOGY:

• OC use has been considered a possible factor behind the increased incidence of FFA because it was first documented in 1994, and a recent genome-wide association study of FFA identified a signal for an association with a variant in CYP1B1.
• The same researchers conducted a gene-environment interaction study with a case-control design involving 489 White female patients (mean age, 65.8 years) with FFA and 34,254 controls, matched for age and genetic ancestry.
• Data were collected from July 2015 to September 2017 and analyzed from October 2022 to December 2023.
• The study aimed to investigate the modulatory effect of OC use on the CYP1B1 variant’s impact on FFA risk, using logistic regression models for analysis.

TAKEAWAY:

• The use of OCs was associated with a 1.9 times greater risk for FFA in individuals with the specific CYP1B1 genetic variant, but there was no association among those with no history of OC use.
• The study suggests a significant gene-environment interaction, indicating that OC use may influence FFA risk in genetically predisposed individuals.

IN PRACTICE:

“This gene-environment interaction analysis suggests that the protective effect of the CYPIB1 missense variant on FFA risk might be mediated by exposure” to OCs, the authors wrote. The study, they added, “underscores the importance of considering genetic predispositions and environmental factors, such as oral contraceptive use, in understanding and managing frontal fibrosing alopecia.”

SOURCE:

Tuntas Rayinda, MD, MSc, PhD, of St. John’s Institute of Dermatology, King’s College London, led the study, which was published online May 29, 2024, in JAMA Dermatology.

LIMITATIONS:

The study’s reliance on self-reported OC use may have introduced recall and differences in ascertainment of OC use between patient and control groups and could have affected the study’s findings. The study also did not collect information on the type of OC used, which could have influenced the observed interaction.

DISCLOSURES:

The study was supported by the British Skin Foundation Young Investigator Award. One investigator reported being a subinvestigator on an alopecia areata study funded by Pfizer. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Mohs surgery appears to be superior to wide local excision (WLE) in patients with high-stage cutaneous squamous cell carcinoma (cSCC), according to findings from a retrospective study. The benefit was seen across all outcome measures, including rates of recurrence, metastasis, and mortality.

These data support Mohs surgery as being the preferred surgical treatment option for high-stage cSCC, commented lead author David M. Wang, MD, Mohs Micrographic Surgery and Dermatologic Oncology Fellow, at Harvard’s Brigham and Women’s Hospital (BWH)/Dana-Farber Cancer Institute, Boston. “We found that across all outcomes, high-stage cSCC treated with WLE had a roughly twofold greater risk for recurrence, metastasis, or disease-specific death compared to Mohs,” he said at the annual meeting of the American College of Mohs Surgery (ACMS), where he presented the results.

External validation using data from a multicenter cSCC research collaboration from 12 contributing sites from across the United States, as well as international sites, was also conducted. “We performed the external validation by comparing results of the BWH-only cohort, which was the primary study, with the full multicenter data and with the full multicenter data minus the BWH cohort, and the findings were nearly identical in all three analyses,” Dr. Wang said.

Although patients diagnosed with cSCC usually have good outcomes, high-stage disease is associated with a higher risk for recurrence, metastasis, and death. Both Mohs surgery and WLE are used to treat cSCC, but a comparison of outcomes has not been well established in the setting of high-stage cSCC. Comparing the two surgical strategies can be problematic, as both patient and/or tumor characteristics can make it difficult to determine which outcomes can be attributed solely to the treatment type.

Mohs Superior Across the Board

In the retrospective cohort study, Dr. Wang and colleagues aimed to compare the results of Mohs surgery and WLE in patients with high-stage cSCC (BWH Staging System T2b or T3) and used statistical methods to balance baseline patient and tumor characteristics.

“To control for confounding by indication — differences in baseline patient or tumor characteristics — that are associated with both the treatment received and outcomes, we used propensity score weighting so that the baseline characteristics were balanced in the two treatment groups,” Dr. Wang told this news organization. “This statistical method aims to simulate randomization in a randomized controlled trial such that any differences in outcomes after propensity score weighting is attributed solely to the treatment received.”

The study used electronic medical records from a single tertiary care academic institution, and 216 patients with high-stage cSCC who had undergone surgery from January 2000 to December 2019 were included in the analysis. The median follow-up time was 33.1 months.

They found that overall, the risk for all adverse outcomes was lower among patients who had undergone Mohs surgery than among those treated with WLE, with the following results: Rates of local recurrence (5-year CI, 10.8% vs 22.1%, respectively; P = .003), nodal metastasis (11.9% vs 19.3%; P = .04), distant metastasis (4.7% vs 9.0%; P = .09), any recurrence (17.0% vs 34.2%; P < .001), and disease-specific death (8.5% vs 20.3%; P = .001).

“The data supports Mohs surgery as the preferred surgical treatment option for high-stage cSCC in accordance with NCCN [National Comprehensive Cancer Network] guidelines for very high-risk cSCC,” Dr. Wang said. He pointed out that the terminology “very high risk” in NCCN equates to “high stage” in other staging systems (BWH T2b or higher, AJCC T3 or higher).

There is still “a substantial proportion” of patients with high-stage cSCC who are eligible for Mohs but are treated with WLE, he added. “Our hope is that these findings provide additional data to support Mohs as the standard of care for primary surgical treatment of high-stage cSCC.”
 

Supports Benefits of Mohs

Weighing in on the research, Thomas E. Rohrer, MD, a dermatologic surgeon in Chestnut Hill, Massachusetts, noted that this was an excellent study that demonstrates benefits of Mohs surgery over straight excision on essentially all outcomes investigated and measured.

“The data clearly shows that Mohs should be used whenever possible,” he said. “There are some patients and facilities that do not have access or timely access to Mohs, so they would likely proceed with standard wide local excision. Otherwise, if there is the capability to perform Mohs, it would be preferred,” he added.

“There is no benefit to a standard excision over Mohs,” Dr. Rohrer emphasized. “If a surgeon is not sure if they have attained clear margins, they could and often do take a little more tissue to be certain.”

Also asked to comment on the data, Chad L. Prather, MD, a dermatologist in Baton Rouge, Louisiana, said, “We know that Mohs has been used for cancers that are not highly staged and we know it’s better than WLE, but this study shows that it is beneficial for higher stage cancers.”

However, he cautioned that unlike early-stage cancers, where Mohs is usually a definitive treatment, with higher stage disease it is a starting point. “As a takeaway, Mohs is superior, but it needs to be followed through,” he said. “These patients need to be closely followed as they are at a high risk for recurrence and metastasis and may need to be worked up for lymph node involvement and need additional therapy going forward.”

Dr. Prather also pointed out that there are circumstances when WLE may be a more suitable treatment. “Mohs is not very good if there is bony involvement,” he said. “This most often happens when the lesion is on the scalp and has invaded the skull. WLE may still be the preferred choice.”

Additionally, Mohs is not the best choice if the tumor is broken into multiple segments. “In these cases, WLE may be preferred,” Dr. Prather added. “But overall, Mohs is one of the best tools we have, and it stands to reason that it works well for high-risk tumors, as this study shows.”

The study was independently supported. Dr. Wang reported no relevant financial relationships. Dr. Rohrer and Dr. Prather had no relevant disclosures.

A version of this article appeared on Medscape.com.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.