MDedge Dermatology

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.

Clinicians should incorporate at least one of three validated instruments to measure signs of atopic dermatitis (AD) in their clinical practice, the authors of a new consensus statement recommended.

These include the Eczema Area and Severity Index (EASI), the Validated Investigator Global Assessment for AD (vIGAAD), and the Investigator’s Global Assessment (IGA) multiplied by or measured concurrently with a body surface area (BSA) assessment.

The recommendations are part of a consensus statement based on an updated systematic review conducted by the Harmonizing Outcome Measures for Eczema Clinical Practice (HOME-CP) initiative, whose goal is to identify validated, feasible outcome instruments designed to measure AD in the clinical setting. In the statement, which was published in JAMA Dermatology on May 22, 2024, corresponding author Eric L. Simpson, MD, MCR, professor of dermatology at Oregon Health & Science University, Portland, and coauthors described HOME-CP as “a ‘pick-and-choose’ list of valid and feasible OMIs [outcome measure instruments] that can be incorporated into the practice setting depending on the particular need of that clinic or health system.”

For the effort, the authors implemented a mixed methods design and incorporated systematic reviews and qualitative consensus methods modeled after the HOME core outcome set initiative, which developed a set of consensus-based core outcome sets for clinical trials and clinical practice. In October of 2022, a daylong in-person consensus exercise was held in Montreal, Canada, where attendees met to reach consensus on recommended instruments to measure AD clinical signs in clinical practice, based on an updated systematic review evaluating the validity of clinical signs instruments.

The review included 22 studies describing 16 instruments that assessed AD clinical signs and an additional 12 variants of instruments. The meeting was attended by 34 individuals from 13 countries, including patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives. Consensus was defined as less than 30% disagreement.

Following their daylong consensus exercise, the stakeholders reached consensus on recommendations to use the EASI, the vIGAAD, and an IGA multiplied or measured alongside a BSA measurement to measure the domain of clinical signs of AD in the clinical practice setting. “The use of multiple IGAs, most with insufficient validation, and the diverse methods used to assess BSA prevented participants from making specific recommendations for the exact IGA/BSA instrument,” the authors wrote. “We recommend that clinicians include at least one of the recommended instruments in their clinical practices and in documentation.” 

They explained that the ideal method of measuring BSA was difficult to assess “because multiple techniques exist for its measurement, including regional percentages, the Rule of Nines, or the handprint method. Most studies did not report which method was performed, and to our knowledge, no studies have been performed in patients with AD that have formally compared them.”

During the consensus exercise, the authors noted, several clinicians “expressed concern whether the EASI was feasible for universal use in clinical practice given its complexity, long completion time, and documentation/calculation requirements.” But clinicians who commonly perform the EASI in clinical practice said that the time it takes to complete this measure “has dropped substantially and now is not a considerable burden,” they wrote, adding that, “studies have shown that with trained investigators, EASI completion times can be as low as nearly 2 minutes.”

The authors acknowledged certain limitations of their recommendations, including the lack of input from primary care clinicians. “It is unknown whether ClinROMs [clinician-reported outcome measures] for AD clinical signs are used in the primary care setting, especially given the large amount of conditions that are managed simultaneously and the ever-increasing number of primary care documentation requirements,” they wrote.

Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, who was asked to comment on the consensus statement, said that with the advent of new, improved, and more expensive medications for AD, “it is ever more important that [the clinical] assessment is reliable and reproducible.”

Insurers “are understandably less willing to rubber-stamp approval of more expensive medications without a reliable standard by which to justify such decisions,” he added. “This is even more important in a disease state like atopic dermatitis that lacks a reliable biomarker. Therefore, one or several practical, reliable, validated severity metrics will help standardize and improve AD care.”

Dr. Sidbury, who cochaired the 2023 American Academy of Dermatology guidelines of care for the management of AD in adults with phototherapy and systemic therapies, added that the instruments evaluated in the review “can be challenging for anyone,” not just primary care providers. “The EASI isn’t that easy, and while there is a learning curve and it ultimately does, like anything, become more efficient in the gathering, it is unclear if non-AD researchers will be willing to invest the time” to routinely use it, he said.

Dr. Simpson and several coauthors reported receiving grants and personal fees from multiple pharmaceutical companies. Dr. Sidbury reported that he serves as an investigator for Regeneron, Galderma, UCB, Castle, and Pfizer; is a consultant for LEO, Lilly, Arcutis, Dermavant, and Pierre Fabre; and a speaker for Beiersdorf.

A version of this article appeared on Medscape.com .

Clinicians should incorporate at least one of three validated instruments to measure signs of atopic dermatitis (AD) in their clinical practice, the authors of a new consensus statement recommended.

These include the Eczema Area and Severity Index (EASI), the Validated Investigator Global Assessment for AD (vIGAAD), and the Investigator’s Global Assessment (IGA) multiplied by or measured concurrently with a body surface area (BSA) assessment.

The recommendations are part of a consensus statement based on an updated systematic review conducted by the Harmonizing Outcome Measures for Eczema Clinical Practice (HOME-CP) initiative, whose goal is to identify validated, feasible outcome instruments designed to measure AD in the clinical setting. In the statement, which was published in JAMA Dermatology on May 22, 2024, corresponding author Eric L. Simpson, MD, MCR, professor of dermatology at Oregon Health & Science University, Portland, and coauthors described HOME-CP as “a ‘pick-and-choose’ list of valid and feasible OMIs [outcome measure instruments] that can be incorporated into the practice setting depending on the particular need of that clinic or health system.”

For the effort, the authors implemented a mixed methods design and incorporated systematic reviews and qualitative consensus methods modeled after the HOME core outcome set initiative, which developed a set of consensus-based core outcome sets for clinical trials and clinical practice. In October of 2022, a daylong in-person consensus exercise was held in Montreal, Canada, where attendees met to reach consensus on recommended instruments to measure AD clinical signs in clinical practice, based on an updated systematic review evaluating the validity of clinical signs instruments.

The review included 22 studies describing 16 instruments that assessed AD clinical signs and an additional 12 variants of instruments. The meeting was attended by 34 individuals from 13 countries, including patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives. Consensus was defined as less than 30% disagreement.

Following their daylong consensus exercise, the stakeholders reached consensus on recommendations to use the EASI, the vIGAAD, and an IGA multiplied or measured alongside a BSA measurement to measure the domain of clinical signs of AD in the clinical practice setting. “The use of multiple IGAs, most with insufficient validation, and the diverse methods used to assess BSA prevented participants from making specific recommendations for the exact IGA/BSA instrument,” the authors wrote. “We recommend that clinicians include at least one of the recommended instruments in their clinical practices and in documentation.” 

They explained that the ideal method of measuring BSA was difficult to assess “because multiple techniques exist for its measurement, including regional percentages, the Rule of Nines, or the handprint method. Most studies did not report which method was performed, and to our knowledge, no studies have been performed in patients with AD that have formally compared them.”

During the consensus exercise, the authors noted, several clinicians “expressed concern whether the EASI was feasible for universal use in clinical practice given its complexity, long completion time, and documentation/calculation requirements.” But clinicians who commonly perform the EASI in clinical practice said that the time it takes to complete this measure “has dropped substantially and now is not a considerable burden,” they wrote, adding that, “studies have shown that with trained investigators, EASI completion times can be as low as nearly 2 minutes.”

The authors acknowledged certain limitations of their recommendations, including the lack of input from primary care clinicians. “It is unknown whether ClinROMs [clinician-reported outcome measures] for AD clinical signs are used in the primary care setting, especially given the large amount of conditions that are managed simultaneously and the ever-increasing number of primary care documentation requirements,” they wrote.

Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, who was asked to comment on the consensus statement, said that with the advent of new, improved, and more expensive medications for AD, “it is ever more important that [the clinical] assessment is reliable and reproducible.”

Insurers “are understandably less willing to rubber-stamp approval of more expensive medications without a reliable standard by which to justify such decisions,” he added. “This is even more important in a disease state like atopic dermatitis that lacks a reliable biomarker. Therefore, one or several practical, reliable, validated severity metrics will help standardize and improve AD care.”

Dr. Sidbury, who cochaired the 2023 American Academy of Dermatology guidelines of care for the management of AD in adults with phototherapy and systemic therapies, added that the instruments evaluated in the review “can be challenging for anyone,” not just primary care providers. “The EASI isn’t that easy, and while there is a learning curve and it ultimately does, like anything, become more efficient in the gathering, it is unclear if non-AD researchers will be willing to invest the time” to routinely use it, he said.

Dr. Simpson and several coauthors reported receiving grants and personal fees from multiple pharmaceutical companies. Dr. Sidbury reported that he serves as an investigator for Regeneron, Galderma, UCB, Castle, and Pfizer; is a consultant for LEO, Lilly, Arcutis, Dermavant, and Pierre Fabre; and a speaker for Beiersdorf.

A version of this article appeared on Medscape.com .

Clinicians should incorporate at least one of three validated instruments to measure signs of atopic dermatitis (AD) in their clinical practice, the authors of a new consensus statement recommended.

These include the Eczema Area and Severity Index (EASI), the Validated Investigator Global Assessment for AD (vIGAAD), and the Investigator’s Global Assessment (IGA) multiplied by or measured concurrently with a body surface area (BSA) assessment.

The recommendations are part of a consensus statement based on an updated systematic review conducted by the Harmonizing Outcome Measures for Eczema Clinical Practice (HOME-CP) initiative, whose goal is to identify validated, feasible outcome instruments designed to measure AD in the clinical setting. In the statement, which was published in JAMA Dermatology on May 22, 2024, corresponding author Eric L. Simpson, MD, MCR, professor of dermatology at Oregon Health & Science University, Portland, and coauthors described HOME-CP as “a ‘pick-and-choose’ list of valid and feasible OMIs [outcome measure instruments] that can be incorporated into the practice setting depending on the particular need of that clinic or health system.”

For the effort, the authors implemented a mixed methods design and incorporated systematic reviews and qualitative consensus methods modeled after the HOME core outcome set initiative, which developed a set of consensus-based core outcome sets for clinical trials and clinical practice. In October of 2022, a daylong in-person consensus exercise was held in Montreal, Canada, where attendees met to reach consensus on recommended instruments to measure AD clinical signs in clinical practice, based on an updated systematic review evaluating the validity of clinical signs instruments.

The review included 22 studies describing 16 instruments that assessed AD clinical signs and an additional 12 variants of instruments. The meeting was attended by 34 individuals from 13 countries, including patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives. Consensus was defined as less than 30% disagreement.

Following their daylong consensus exercise, the stakeholders reached consensus on recommendations to use the EASI, the vIGAAD, and an IGA multiplied or measured alongside a BSA measurement to measure the domain of clinical signs of AD in the clinical practice setting. “The use of multiple IGAs, most with insufficient validation, and the diverse methods used to assess BSA prevented participants from making specific recommendations for the exact IGA/BSA instrument,” the authors wrote. “We recommend that clinicians include at least one of the recommended instruments in their clinical practices and in documentation.” 

They explained that the ideal method of measuring BSA was difficult to assess “because multiple techniques exist for its measurement, including regional percentages, the Rule of Nines, or the handprint method. Most studies did not report which method was performed, and to our knowledge, no studies have been performed in patients with AD that have formally compared them.”

During the consensus exercise, the authors noted, several clinicians “expressed concern whether the EASI was feasible for universal use in clinical practice given its complexity, long completion time, and documentation/calculation requirements.” But clinicians who commonly perform the EASI in clinical practice said that the time it takes to complete this measure “has dropped substantially and now is not a considerable burden,” they wrote, adding that, “studies have shown that with trained investigators, EASI completion times can be as low as nearly 2 minutes.”

The authors acknowledged certain limitations of their recommendations, including the lack of input from primary care clinicians. “It is unknown whether ClinROMs [clinician-reported outcome measures] for AD clinical signs are used in the primary care setting, especially given the large amount of conditions that are managed simultaneously and the ever-increasing number of primary care documentation requirements,” they wrote.

Robert Sidbury, MD, MPH, chief of the division of dermatology at Seattle Children’s Hospital, who was asked to comment on the consensus statement, said that with the advent of new, improved, and more expensive medications for AD, “it is ever more important that [the clinical] assessment is reliable and reproducible.”

Insurers “are understandably less willing to rubber-stamp approval of more expensive medications without a reliable standard by which to justify such decisions,” he added. “This is even more important in a disease state like atopic dermatitis that lacks a reliable biomarker. Therefore, one or several practical, reliable, validated severity metrics will help standardize and improve AD care.”

Dr. Sidbury, who cochaired the 2023 American Academy of Dermatology guidelines of care for the management of AD in adults with phototherapy and systemic therapies, added that the instruments evaluated in the review “can be challenging for anyone,” not just primary care providers. “The EASI isn’t that easy, and while there is a learning curve and it ultimately does, like anything, become more efficient in the gathering, it is unclear if non-AD researchers will be willing to invest the time” to routinely use it, he said.

Dr. Simpson and several coauthors reported receiving grants and personal fees from multiple pharmaceutical companies. Dr. Sidbury reported that he serves as an investigator for Regeneron, Galderma, UCB, Castle, and Pfizer; is a consultant for LEO, Lilly, Arcutis, Dermavant, and Pierre Fabre; and a speaker for Beiersdorf.

A version of this article appeared on Medscape.com .

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.