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Rosacea: Ivermectin’s Benefits May Include Impact on Skin Microbiome
TOPLINE:
in a small study.
METHODOLOGY:
- In this single-center, open label study, 10 adults (mean age, 66.4 years) with papulopustular rosacea were treated with 1% ivermectin cream daily for 12 weeks.
- Skin swabs from lesional and nonlesional sites were collected at baseline and after 3 months of treatment to assess changes in the bacterial microbiome and the density of Demodex mites.
- The average baseline total papule count was 26.9, and the Clinician’s Erythema Assessment (CEA) score was 2 (average value on a scale of 0-4 from five locations on the face).
- For comparison, baseline swabs were taken from 10 healthy age-matched individuals.
TAKEAWAY:
- The density of Demodex mites was significantly reduced on lesional skin (P = .002) with topical ivermectin, which has anthelmintic effects against Demodex and is an effective treatment for rosacea.
- The absolute abundance of S epidermidis increased after ivermectin treatment on lesional skin (P = .039), while no changes were seen in Cutibacterium acnes.
- No changes were noted on nonlesional skin in the patients with rosacea.
- Topical ivermectin also reduced the number of papules and CEA scores (both P = .002) in individuals with rosacea.
IN PRACTICE:
“Treatment with topical ivermectin may improve the symptoms of rosacea through modulation of the skin microbiome beyond decreasing Demodex,” the authors concluded. “The results of this study,” they added, “provide valuable insights into the intricacies of the cutaneous microbiome in the pathophysiology of rosacea and highlight the potential therapeutic interventions targeting the skin microbiome.”
SOURCE:
The study was led by Teruaki Nakatsuji, PhD, of the department of dermatology, University of California, San Diego. It was published online on October 29 in the Journal of Investigative Dermatology.
LIMITATIONS:
The small sample size of 10 patients with rosacea limits the generalizability of the findings, and the study’s open-label design may introduce bias in the clinical assessments. Further research with larger sample sizes and randomized controlled trials is needed to confirm these findings.
DISCLOSURES:
This work was funded by a grant from the National Rosacea Society. One author disclosed being the cofounder and consultant, with equity interest in MatriSys Bioscience. The other authors reported no competing interests.
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 first appeared on Medscape.com.
TOPLINE:
in a small study.
METHODOLOGY:
- In this single-center, open label study, 10 adults (mean age, 66.4 years) with papulopustular rosacea were treated with 1% ivermectin cream daily for 12 weeks.
- Skin swabs from lesional and nonlesional sites were collected at baseline and after 3 months of treatment to assess changes in the bacterial microbiome and the density of Demodex mites.
- The average baseline total papule count was 26.9, and the Clinician’s Erythema Assessment (CEA) score was 2 (average value on a scale of 0-4 from five locations on the face).
- For comparison, baseline swabs were taken from 10 healthy age-matched individuals.
TAKEAWAY:
- The density of Demodex mites was significantly reduced on lesional skin (P = .002) with topical ivermectin, which has anthelmintic effects against Demodex and is an effective treatment for rosacea.
- The absolute abundance of S epidermidis increased after ivermectin treatment on lesional skin (P = .039), while no changes were seen in Cutibacterium acnes.
- No changes were noted on nonlesional skin in the patients with rosacea.
- Topical ivermectin also reduced the number of papules and CEA scores (both P = .002) in individuals with rosacea.
IN PRACTICE:
“Treatment with topical ivermectin may improve the symptoms of rosacea through modulation of the skin microbiome beyond decreasing Demodex,” the authors concluded. “The results of this study,” they added, “provide valuable insights into the intricacies of the cutaneous microbiome in the pathophysiology of rosacea and highlight the potential therapeutic interventions targeting the skin microbiome.”
SOURCE:
The study was led by Teruaki Nakatsuji, PhD, of the department of dermatology, University of California, San Diego. It was published online on October 29 in the Journal of Investigative Dermatology.
LIMITATIONS:
The small sample size of 10 patients with rosacea limits the generalizability of the findings, and the study’s open-label design may introduce bias in the clinical assessments. Further research with larger sample sizes and randomized controlled trials is needed to confirm these findings.
DISCLOSURES:
This work was funded by a grant from the National Rosacea Society. One author disclosed being the cofounder and consultant, with equity interest in MatriSys Bioscience. The other authors reported no competing interests.
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 first appeared on Medscape.com.
TOPLINE:
in a small study.
METHODOLOGY:
- In this single-center, open label study, 10 adults (mean age, 66.4 years) with papulopustular rosacea were treated with 1% ivermectin cream daily for 12 weeks.
- Skin swabs from lesional and nonlesional sites were collected at baseline and after 3 months of treatment to assess changes in the bacterial microbiome and the density of Demodex mites.
- The average baseline total papule count was 26.9, and the Clinician’s Erythema Assessment (CEA) score was 2 (average value on a scale of 0-4 from five locations on the face).
- For comparison, baseline swabs were taken from 10 healthy age-matched individuals.
TAKEAWAY:
- The density of Demodex mites was significantly reduced on lesional skin (P = .002) with topical ivermectin, which has anthelmintic effects against Demodex and is an effective treatment for rosacea.
- The absolute abundance of S epidermidis increased after ivermectin treatment on lesional skin (P = .039), while no changes were seen in Cutibacterium acnes.
- No changes were noted on nonlesional skin in the patients with rosacea.
- Topical ivermectin also reduced the number of papules and CEA scores (both P = .002) in individuals with rosacea.
IN PRACTICE:
“Treatment with topical ivermectin may improve the symptoms of rosacea through modulation of the skin microbiome beyond decreasing Demodex,” the authors concluded. “The results of this study,” they added, “provide valuable insights into the intricacies of the cutaneous microbiome in the pathophysiology of rosacea and highlight the potential therapeutic interventions targeting the skin microbiome.”
SOURCE:
The study was led by Teruaki Nakatsuji, PhD, of the department of dermatology, University of California, San Diego. It was published online on October 29 in the Journal of Investigative Dermatology.
LIMITATIONS:
The small sample size of 10 patients with rosacea limits the generalizability of the findings, and the study’s open-label design may introduce bias in the clinical assessments. Further research with larger sample sizes and randomized controlled trials is needed to confirm these findings.
DISCLOSURES:
This work was funded by a grant from the National Rosacea Society. One author disclosed being the cofounder and consultant, with equity interest in MatriSys Bioscience. The other authors reported no competing interests.
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 first appeared on Medscape.com.
A young adult with a 1-year history of erythema, papules, and pustules on her cheeks and skin
. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.
Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.
Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.
Isotretinoin has been shown to be effective in treating pyoderma faciale by significantly reducing inflammation and scarring. This is imperative because the scarring from pyoderma faciale can be disfiguring and psychologically harmful for patients. Therefore, an early diagnosis and effective treatment method are essential in preventing these scars and improving patients’ confidence and overall dermatological care.
This patient’s initial bacterial culture was negative. She was treated with a course of low dose isotretinoin. Prednisone was initiated two weeks before starting isotretinoin and then was tapered off during the first month of isotretinoin treatment. The patient was also started on spironolactone. The course of isotretinoin was 9 months. She has remained clear and still takes oral contraceptive pills and low dose spironolactone.
This case and the photos were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Donna Bilu Martin, MD, of Premier Dermatology, MD, Aventura, Florida. The column was edited by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.
Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.
Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.
. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.
Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.
Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.
Isotretinoin has been shown to be effective in treating pyoderma faciale by significantly reducing inflammation and scarring. This is imperative because the scarring from pyoderma faciale can be disfiguring and psychologically harmful for patients. Therefore, an early diagnosis and effective treatment method are essential in preventing these scars and improving patients’ confidence and overall dermatological care.
This patient’s initial bacterial culture was negative. She was treated with a course of low dose isotretinoin. Prednisone was initiated two weeks before starting isotretinoin and then was tapered off during the first month of isotretinoin treatment. The patient was also started on spironolactone. The course of isotretinoin was 9 months. She has remained clear and still takes oral contraceptive pills and low dose spironolactone.
This case and the photos were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Donna Bilu Martin, MD, of Premier Dermatology, MD, Aventura, Florida. The column was edited by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.
Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.
Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.
. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.
Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.
Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.
Isotretinoin has been shown to be effective in treating pyoderma faciale by significantly reducing inflammation and scarring. This is imperative because the scarring from pyoderma faciale can be disfiguring and psychologically harmful for patients. Therefore, an early diagnosis and effective treatment method are essential in preventing these scars and improving patients’ confidence and overall dermatological care.
This patient’s initial bacterial culture was negative. She was treated with a course of low dose isotretinoin. Prednisone was initiated two weeks before starting isotretinoin and then was tapered off during the first month of isotretinoin treatment. The patient was also started on spironolactone. The course of isotretinoin was 9 months. She has remained clear and still takes oral contraceptive pills and low dose spironolactone.
This case and the photos were submitted by Ms. Towe, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Donna Bilu Martin, MD, of Premier Dermatology, MD, Aventura, Florida. The column was edited by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.
Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.
Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.
Migraine Drug Reduces Rosacea Flushing, Erythema in Small Study
In. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.
The study was published in JAMA Dermatology.
“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.
Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Spotlight on CGRP
Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.
For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.
Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.
Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
Questions Over QOL Data
“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.
Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).
No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.
However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.
Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”
Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.
Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.
A version of this article appeared on Medscape.com.
In. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.
The study was published in JAMA Dermatology.
“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.
Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Spotlight on CGRP
Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.
For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.
Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.
Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
Questions Over QOL Data
“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.
Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).
No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.
However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.
Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”
Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.
Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.
A version of this article appeared on Medscape.com.
In. Skin-related quality-of-life (QOL) measures also improved, albeit modestly.
The study was published in JAMA Dermatology.
“The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat,” Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. “As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea.” Dr. Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.
Guy F. Webster, MD, PhD, clinical professor of dermatology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, added, “The interesting thing about this study is that it gives us a new target to think about for therapy. But it’s a long way from saying we can use it tomorrow.” He was not involved with the study but was also asked to comment on the findings.
Spotlight on CGRP
Rosacea’s pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea.
For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments.
Participants received 3-monthly 140-mg doses of erenumab, which is approved by the Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose.
Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
Questions Over QOL Data
“Although there were significant decreases in flushing and erythema,” wrote John S. Barbieri, MD, MBA, in an accompanying Editor’s Note, “the present study had relatively modest improvements in quality of life.” He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women’s Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology.
Compared with baseline (6.22), mean Dermatology Life Quality Index scores fell 2.08 points and 2.73 points at weeks 8 and 20, respectively (P = .004 and .003). At the same intervals, the mean baseline Rosacea Quality of Life score (48.22) decreased by 2.58 points and 4.14 points, respectively (P = .04 and .02).
No significant changes appeared in gauges of anxiety and depression. These findings, authors wrote, could stem from their decision to omit a follow-up visit at week 12 — where they may have seen mental-health effects which disappeared by week 20 — in response to patients’ logistical concerns.
However, Dr. Webster questioned the value of QOL measurements in rosacea. “Quality-of-life measures are blunt instruments,” he explained, and reducing severe itching or chronic pain improves the lives of affected patients. “But what question are you going to ask to tease out whether being less red-cheeked has made someone’s life easier? It’s not a problem that lends itself to quality-of-life assessments.” Moreover, he said, regulators who increasingly require such measures in clinical trials ignore this point, creating challenges for drug developers and researchers.
Because the study was neither blinded nor controlled, Dr. Webster suggested considering it a tantalizing proof of concept. “If I were putting money into a CGRP inhibitor, I’d want at least a small, placebo-controlled, double-blinded study.”
Study authors and Dr. Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Dr. Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.
Dr. Wienholtz reported no relevant financial interests. Dr. Barbieri had no related disclosures. Dr. Webster reported no relevant financial interests. Dr. Graber reported no conflicts related to erenumab but consults for other companies with rosacea-related products including Galderma. The study was supported by and conducted in collaboration with Novartis Pharma AG. Additional funding came from the Novo Nordisk Foundation and the Lundbeck Foundation.
A version of this article appeared on Medscape.com.
FROM JAMA DERMATOLOGY
A Neurotoxin, an Antidepressant, and More Emerging Options for Treating Rosacea
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
ORLANDO, FLORIDA — At the same time, there is new recognition that systemic inflammation can occur with rosacea, and targeting treatment to the phenotype continues to gain steam as a way to help people with this difficult-to-manage condition.
“Anyone here think they’ve got rosacea under control? No, I wish — not yet,” Diane Dr. Thiboutot, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.
Botulinum Toxin Benefits
With that in mind, Dr. Thiboutot highlighted emerging therapies for treating rosacea. “Last year, there were a couple of reports … looking at the use of botulinum toxin injections for patients with rosacea,” said Dr. Thiboutot, professor of dermatology and vice chair for research in the Department of Dermatology at Penn State College of Medicine, Hershey, Pennsylvania.
One report describes the case of a woman with rosacea who had severe recurrent episodes of erythema and flushing. She also experienced occasional papules and pustules and had been recalcitrant to multiple treatments for rosacea, according to the report published in the Journal of Drugs in Dermatology in June 2023. The patient was treated with a total of 150-180 units of botulinum toxin administered as 3-6 units spaced 1 cm apart every 2-4 months. She was “eventually maintained every 6 months with excellent improvement,” Dr. Thiboutot said.
In another case, a man with refractory vascular and papulopustular rosacea was treated with half of a unit of botulinum toxin spaced every 0.5 cm. Images taken at baseline, 1 month, and 3 months after treatment demonstrated improvements, as reported in June 2023.
Regarding botulinum toxin for rosacea, Dr. Thiboutot said, “it’s a very interesting thing to think about.”
Susan Weinkle, MD, ODAC conference cochair, session moderator, and collaborative associate professor of dermatology at the University of South Florida, Tampa, Florida, agreed. “I do think it holds some interesting potential,” she said. “How good are your hands? Because administering 0.5-unit injections evenly is a little bit challenging.”
However, one approach that might help is “if we could be a little more innovative like they are in Europe.” Physicians in Europe can use a metered syringe, one where they dial in the exact amount per injection, which allows them to be consistent, she added.
With rosacea erythema, Dr. Thiboutot noted, a spotted effect can result if injections are not administered uniformly.
Potential Role for Paroxetine
The antidepressant paroxetine, a potent selective serotonin reuptake inhibitor, could be an effective treatment for refractory erythema of rosacea, Dr. Thiboutot said. It is approved for treating depression, obsessive-compulsive disorder, and social phobia. The agent has also shown effectiveness in alleviating hot flashes associated with vascular dysregulation in menopause.
Uptake in serotonin and changes in receptors are closely related to vascular dilation and constriction, Dr. Thiboutot added, so paroxetine “may be beneficial in treating vascular dysfunction” including in people with rosacea. Evidence to support this potential approach comes from the primary results of a randomized controlled trial published in June 2023. Based on the results, the researchers concluded that paroxetine “appears to be an efficacious and well-tolerated treatment for refractory erythema in rosacea.”
In the trial, almost 43% of people treated with paroxetine met the primary endpoint for improving recalcitrant erythema at week 12 compared with almost 21% who took a placebo, a statistically significant difference.
Heparan Sulfate Analog in a Cream
Evidence suggests that a low-molecular-weight heparan sulfate analog is another agent that holds potential for treating rosacea. For example, a 2023 randomized controlled trial evaluated the immune response in rosacea, focusing on a specific cathelicidin peptide called LL-37 that activates an inflammasome in rosacea. Low-molecular-weight heparan sulfate holds the potential to inhibit LL-37 activity, as LL-37 is inhibited by binding to heparan sulfate, a cell surface glycosaminoglycan.
The study of 16 people assessed the ability of the analog to modulate this response; they were also treated with the pulsed dye laser. Participants who applied a dermal repair cream that contained this ingredient experienced a one-grade reduction in erythema at weeks 4 and 8 compared with a control group applying a moisturizer.
A Growing Case for Systemic Inflammation
In the meantime, treating rosacea with more traditional therapies remains challenging.
But there’s hope. Success has been reported in the few years since an expert panel recommended treating based on phenotype — a treat-what-you-see approach, Dr. Thiboutot said.
“We don’t have a single treatment that is one-size-fits-all. We have to individualize our treatment [based] more on what we are seeing and what the patient is experiencing.”
Eventually, therapies to treat systemic inflammation could provide benefits as well. As with hidradenitis suppurativa and psoriasis, “there’s evidence of systemic inflammation in some of our rosacea patients,” Dr. Thiboutot said.
For example, researchers compared blood taken from people with and without rosacea and found increased levels of some inflammatory markers among participants with the condition.
The retrospective study published in June 2023 in Scientific Reports included 100 patients with rosacea and 58 controls. The investigators found significantly higher elevations in the SII index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels in the patients with rosacea.
“There was no significant link between the severity of rosacea and the ESR, CRP, or SII index values, Dr. Thiboutot added. “This study suggests inflammation beyond the skin in rosacea patients.”
For more guidance on treating rosacea through standard management options, including how to tailor therapy to each individual, she recommended the 2019 Update by the National Rosacea Society Expert Committee. “It’s a nice quick way to see, based on expert opinion, the most effective treatments and what the evidence base is,” said Dr. Thiboutot, lead author of the paper, published in the Journal of the American Academy of Dermatology in February 2020.
Dr. Thiboutot reported no relevant financial relationships.
FROM ODAC 2024
National Rosacea Society adds imprimatur to skin products
, according to a press release from the NRS.
The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.
Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.
Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.
Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.
Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.
More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.
, according to a press release from the NRS.
The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.
Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.
Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.
Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.
Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.
More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.
, according to a press release from the NRS.
The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.
Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.
Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.
Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.
Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.
More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.
A Look at the Evidence Linking Diet to Skin Conditions
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Amid all the hype, claims, and confusion, there is evidence linking some foods and drinks to an increased risk for acne, psoriasis, atopic dermatitis, rosacea, and other common skin conditions. So, what is the connection in each case? And how can people with any of these skin conditions potentially improve their health and quality of life with dietary changes?
What is clear is that there has been an explosion of interest in learning which foods can improve or worsen skin issues in recent years. It’s a good idea to familiarize yourself with the research and also to Google ‘diet’ and ‘skin’, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas for Medical Sciences, Little Rock. “As practitioners, we should be well prepared to talk about what patients want to talk about.”
Acne
One of the major areas of interest is diet and acne. “We’ve all heard sugar and dairy are bad, and the Western diet is high in sugar and dairy,” Dr. Shi said at the ODAC Dermatology, Aesthetic & Surgical Conference.
Dairy, red meat, and carbohydrates can break down into leucine, an essential amino acid found in protein. Leucine and sugar together, in turn, can produce insulin and insulin-like growth factor 1 (IGF-1), which, through different pathways, can reach the androgen receptors throughout the body, including the skin. This results in sebogenesis, lipogenesis, and keratinization, which triggers follicular inflammation and results in more of the acne-causing bacteria Cutibacterium acnes.
Milk and other dairy products also can increase IGF-1 levels, which can alter hormonal mediators and increase acne.
Not all types of dairy milk are created equal, however, when it comes to acne. Dr. Shi wondered why 2% milk has overall color and nutritional content very similar to that of whole milk. “I looked into this.” She discovered that when milk manufacturers remove the fat, they often add whey proteins to restore some nutrients. Whey protein can increase acne, Dr. Shi added.
“So, if you’re going to choose any milk to drink, I think from an acne perspective, it’s better to use whole milk. If you can get it organic, even better.” Skim milk is the most acnegenic, she said.
Psoriasis
A systematic review of 55 studies evaluating diet and psoriasis found obesity can be an exacerbating factor. The strongest evidence for dietary weight reduction points to a hypocaloric diet in people with overweight or obesity, according to the review. Other evidence suggests alcohol can lower response to treatment and is linked with more severe psoriasis. Furthermore, a gluten-free diet or vitamin D supplements can help some subpopulations of people with psoriasis.
“An overwhelming majority of our psoriasis patients are vitamin D deficient,” Dr. Shi said.
The National Psoriasis Foundation (NPF) publishes dietary modification guidelines, updated as recently as November 2023. The NPF states that “there is no diet that will cure psoriatic disease, but there are many ways in which eating healthful food may lessen the severity of symptoms and play a role in lowering the likelihood of developing comorbidities.”
Healthier choices include fruits, vegetables, whole grains, and fat-free or low-fat dairy products. Include lean meats, poultry, fish, beans, eggs, and nuts. Adherence to a Mediterranean diet has been linked to a lower severity of psoriasis.
Atopic Dermatitis
Atopic dermatitis (AD) is “one of the prototypical diseases related to diet,” Dr. Shi said. A different meta-analysis looked at randomized controlled trials of synbiotics (a combination of prebiotics and probiotics) for treatment of AD.
These researchers found that synbiotics do not prevent AD, but they can help treat it in adults and children older than 1 year. In addition, synbiotics are more beneficial than probiotics in treating the condition, although there are no head-to-head comparison studies. In addition, the meta-analysis found that prebiotics alone can lower AD severity.
However, Dr. Shi said, there are no recommendations from the American Academy of Dermatology (AAD) on prebiotics or probiotics for AD, and the AAD does not recommend any supplement or essential oil for AD.
In a 2022 review, investigators ranked the efficacy of different supplements for AD based on available evidence. They found the greatest benefit associated with vitamin D supplementation, followed by vitamin E, probiotics, hemp seed oil, histidine, and oolong tea. They also noted the ‘Six Food Elimination Diet and Autoimmune Protocol’ featured the least amount of evidence to back it up.
Rosacea
Rosacea appears to be caused by “all the fun things in life” like sunlight, alcohol, chocolate, spicy foods, and caffeine, Dr. Shi said. In people with rosacea, they can cause facial flushing, edema, burning, and an inflammatory response.
Certain foods can activate skin receptors and sensory neurons, which can release neuropeptides that act on mast cells in blood that lead to flushing. The skin-gut axis may also be involved, evidence suggests. “And that is why food has a pretty profound impact on rosacea,” Dr. Shi said.
Dr. Shi reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Impact of Pregnancy on Rosacea Unpredictable, Study Suggests
TOPLINE:
Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.
METHODOLOGY:
- Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
- Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.
TAKEAWAY:
- The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
- All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
- Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
- Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.
IN PRACTICE:
“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.
SOURCE:
Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.
LIMITATIONS:
The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.
METHODOLOGY:
- Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
- Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.
TAKEAWAY:
- The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
- All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
- Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
- Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.
IN PRACTICE:
“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.
SOURCE:
Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.
LIMITATIONS:
The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Among women diagnosed with rosacea, the impact of pregnancy on the disease is unpredictable.
METHODOLOGY:
- Researchers conducted a telephone survey of 39 women with a diagnosis of rosacea in the electronic medical records prior to the onset of pregnancy who had been admitted to Oregon Health & Science University for labor and delivery from June 27, 2015, to June 27, 2020.
- Patient global assessment of clear (0), mild (1), moderate (2), or severe (3) rosacea was rated across five timepoints: 1-3 months preconception; first, second, and third trimesters; and 6 weeks postpartum.
TAKEAWAY:
- The mean age of the survey participants was 35.5 years, the mean gestational age at delivery was 39.4 weeks, and most had singleton pregnancies.
- All but one study participant (97.4%) reported symptoms of erythematotelangiectatic rosacea, while 26 (67%) reported symptoms of papulopustular rosacea.
- Nearly half of the participants (19, 48.7%) said their rosacea worsened during pregnancy, 13 (33.3%) reported no change in rosacea severity during pregnancy, and 7 (17.9%) reported that their rosacea improved during pregnancy.
- Before conceiving, the mean rosacea severity score among participants was mild (1.10; 95% CI, 0.92-1.29) and did not change significantly over time, a reflection of individual variations. In addition, 83.3% of participants did not use prescription rosacea treatments prior to pregnancy, and 89.6% did not use them during pregnancy.
IN PRACTICE:
“Rosacea, like acne, lacks a predictable group effect, and instead, each individual may have a different response to the physiologic changes of pregnancy,” the authors concluded.
SOURCE:
Genevieve Benedetti, MD, MPP, of the Department of Dermatology at Oregon Health & Science University, Portland, Oregon, led the research, published as a research letter in the International Journal of Women’s Dermatology.
LIMITATIONS:
The small sample size, single-center design, and overall prevalence of mild disease limit the ability to detect change.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
US Dermatologic Drug Approvals Rose Between 2012 and 2022
TOPLINE:
METHODOLOGY:
- Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
- In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
- They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.
TAKEAWAY:
- The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
- Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
- An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
- Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.
IN PRACTICE:
While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.
SOURCE:
First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.
LIMITATIONS:
They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.
DISCLOSURES:
Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
- In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
- They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.
TAKEAWAY:
- The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
- Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
- An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
- Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.
IN PRACTICE:
While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.
SOURCE:
First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.
LIMITATIONS:
They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.
DISCLOSURES:
Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
- In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
- They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.
TAKEAWAY:
- The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
- Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
- An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
- Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.
IN PRACTICE:
While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.
SOURCE:
First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.
LIMITATIONS:
They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.
DISCLOSURES:
Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.
A version of this article appeared on Medscape.com.
Topical ivermectin study sheds light on dysbiosis in rosacea
, according to a report presented at the recent European Academy of Dermatology and Venereology (EADV) 2023 Congress.
“This is the first hint that the host’s cutaneous microbiome plays a secondary role in the immunopathogenesis of rosacea,” said Bernard Homey, MD, director of the department of dermatology at University Hospital Düsseldorf in Germany.
“In rosacea, we are well aware of trigger factors such as stress, UV light, heat, cold, food, and alcohol,” he said. “We are also well aware that there is an increase in Demodex mites in the pilosebaceous unit.”
Research over the past decade has also started to look at the potential role of the skin microbiome in the disease process, but answers have remained “largely elusive,” Dr. Homey said.
Ivermectin helps, but how?
Ivermectin 1% cream (Soolantra) has been approved by the U.S. Food and Drug Administration since 2014 for the treatment of the inflammatory lesions that are characteristic of rosacea, but its mechanism of action is not clear.
Dr. Homey presented the results of a study of 61 patients designed to look at how ivermectin might be working in the treatment of people with rosacea and investigate if there was any relation to the skin microbiome and transcriptome of patients.
The trial included 41 individuals with papulopustular rosacea and 20 individuals who did not have rosacea. For all patients, surface skin biopsies were performed twice 30 days apart using cyanoacrylate glue; patients with rosacea were treated with topical ivermectin 1% between biopsies. Skin samples obtained at day 0 and day 30 were examined under the microscope, and Demodex counts (mites/cm2) of skin and RNA sequencing of the cutaneous microbiome were undertaken.
The mean age of the patients with rosacea was 54.9 years, and the mean Demodex counts before and after treatment were a respective 7.2 cm2 and 0.9 cm2.
Using the Investigator’s General Assessment to assess the severity of rosacea, Homey reported that 43.9% of patients with rosacea had a decrease in scores at day 30, indicating improvement.
In addition, topical ivermectin resulted in a marked or total decrease in Demodex mite density for 87.5% of patients (n = 24) who were identified as having the mites.
Skin microbiome changes seen
As a form of quality control, skin microbiome changes among the patients were compared with control patients using 16S rRNA sequencing.
“The taxa we find within the cutaneous niche of inflammatory lesions of rosacea patients are significantly different from healthy volunteers,” Dr. Homey said.
Cutibacterium species are predominant in healthy control persons but are not present when there is inflammation in patients with rosacea. Instead, staphylococcus species “take over the niche, similar to atopic dermatitis,” he noted.
Looking at how treatment with ivermectin influences the organisms, the decrease in C. acnes seen in patients with rosacea persisted despite treatment, and the abundance of Staphylococcus epidermidis, S. hominis, and S. capitis increased further. This suggests a possible protective or homeostatic role of C. acnes but a pathogenic role for staphylococci, explained Dr. Homey.
“Surprisingly, although inflammatory lesions decrease, patients get better, the cutaneous microbiome does not revert to homeostatic conditions during topical ivermectin treatment,” he observed.
There is, of course, variability among individuals.
Dr. Homey also reported that Snodgrassella alvi – a microorganism believed to reside in the gut of Demodex folliculorum mites – was found in the skin microbiome of patients with rosacea before but not after ivermectin treatment. This may mean that this microorganism could be partially triggering inflammation in rosacea patients.
Looking at the transcriptome of patients, Dr. Homey said that there was downregulation of distinct genes that might make for more favorable conditions for Demodex mites.
Moreover, insufficient upregulation of interleukin-17 pathways might be working together with barrier defects in the skin and metabolic changes to “pave the way” for colonization by S. epidermidis.
Pulling it together
Dr. Homey and associates conclude in their abstract that the findings “support that rosacea lesions are associated with dysbiosis.”
Although treatment with ivermectin did not normalize the skin’s microbiome, it was associated with a decrease in Demodex mite density and the reduction of microbes associated with Demodex.
Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra in Portugal, who cochaired the late-breaking news session where the data were presented, asked whether healthy and affected skin in patients with rosacea had been compared, rather than comparing the skin of rosacea lesions with healthy control samples.
“No, we did not this, as this is methodologically a little bit more difficult,” Dr. Homey responded.
Also cochairing the session was Michel Gilliet, MD, chair of the department of dermatology at the University Hospital CHUV in Lausanne, Switzerland. He commented that these “data suggest that there’s an intimate link between Demodex and the skin microbiota and dysbiosis in in rosacea.”
Dr. Gilliet added: “You have a whole dysbiosis going on in rosacea, which is probably only dependent on these bacteria.”
It would be “very interesting,” as a “proof-of-concept” study, to look at whether depleting Demodex would also delete S. alvi, he suggested.
The study was funded by Galderma. Dr. Homey has acted as a consultant, speaker or investigator for many pharmaceutical companies including Galderma.
A version of this article first appeared on Medscape.com.
, according to a report presented at the recent European Academy of Dermatology and Venereology (EADV) 2023 Congress.
“This is the first hint that the host’s cutaneous microbiome plays a secondary role in the immunopathogenesis of rosacea,” said Bernard Homey, MD, director of the department of dermatology at University Hospital Düsseldorf in Germany.
“In rosacea, we are well aware of trigger factors such as stress, UV light, heat, cold, food, and alcohol,” he said. “We are also well aware that there is an increase in Demodex mites in the pilosebaceous unit.”
Research over the past decade has also started to look at the potential role of the skin microbiome in the disease process, but answers have remained “largely elusive,” Dr. Homey said.
Ivermectin helps, but how?
Ivermectin 1% cream (Soolantra) has been approved by the U.S. Food and Drug Administration since 2014 for the treatment of the inflammatory lesions that are characteristic of rosacea, but its mechanism of action is not clear.
Dr. Homey presented the results of a study of 61 patients designed to look at how ivermectin might be working in the treatment of people with rosacea and investigate if there was any relation to the skin microbiome and transcriptome of patients.
The trial included 41 individuals with papulopustular rosacea and 20 individuals who did not have rosacea. For all patients, surface skin biopsies were performed twice 30 days apart using cyanoacrylate glue; patients with rosacea were treated with topical ivermectin 1% between biopsies. Skin samples obtained at day 0 and day 30 were examined under the microscope, and Demodex counts (mites/cm2) of skin and RNA sequencing of the cutaneous microbiome were undertaken.
The mean age of the patients with rosacea was 54.9 years, and the mean Demodex counts before and after treatment were a respective 7.2 cm2 and 0.9 cm2.
Using the Investigator’s General Assessment to assess the severity of rosacea, Homey reported that 43.9% of patients with rosacea had a decrease in scores at day 30, indicating improvement.
In addition, topical ivermectin resulted in a marked or total decrease in Demodex mite density for 87.5% of patients (n = 24) who were identified as having the mites.
Skin microbiome changes seen
As a form of quality control, skin microbiome changes among the patients were compared with control patients using 16S rRNA sequencing.
“The taxa we find within the cutaneous niche of inflammatory lesions of rosacea patients are significantly different from healthy volunteers,” Dr. Homey said.
Cutibacterium species are predominant in healthy control persons but are not present when there is inflammation in patients with rosacea. Instead, staphylococcus species “take over the niche, similar to atopic dermatitis,” he noted.
Looking at how treatment with ivermectin influences the organisms, the decrease in C. acnes seen in patients with rosacea persisted despite treatment, and the abundance of Staphylococcus epidermidis, S. hominis, and S. capitis increased further. This suggests a possible protective or homeostatic role of C. acnes but a pathogenic role for staphylococci, explained Dr. Homey.
“Surprisingly, although inflammatory lesions decrease, patients get better, the cutaneous microbiome does not revert to homeostatic conditions during topical ivermectin treatment,” he observed.
There is, of course, variability among individuals.
Dr. Homey also reported that Snodgrassella alvi – a microorganism believed to reside in the gut of Demodex folliculorum mites – was found in the skin microbiome of patients with rosacea before but not after ivermectin treatment. This may mean that this microorganism could be partially triggering inflammation in rosacea patients.
Looking at the transcriptome of patients, Dr. Homey said that there was downregulation of distinct genes that might make for more favorable conditions for Demodex mites.
Moreover, insufficient upregulation of interleukin-17 pathways might be working together with barrier defects in the skin and metabolic changes to “pave the way” for colonization by S. epidermidis.
Pulling it together
Dr. Homey and associates conclude in their abstract that the findings “support that rosacea lesions are associated with dysbiosis.”
Although treatment with ivermectin did not normalize the skin’s microbiome, it was associated with a decrease in Demodex mite density and the reduction of microbes associated with Demodex.
Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra in Portugal, who cochaired the late-breaking news session where the data were presented, asked whether healthy and affected skin in patients with rosacea had been compared, rather than comparing the skin of rosacea lesions with healthy control samples.
“No, we did not this, as this is methodologically a little bit more difficult,” Dr. Homey responded.
Also cochairing the session was Michel Gilliet, MD, chair of the department of dermatology at the University Hospital CHUV in Lausanne, Switzerland. He commented that these “data suggest that there’s an intimate link between Demodex and the skin microbiota and dysbiosis in in rosacea.”
Dr. Gilliet added: “You have a whole dysbiosis going on in rosacea, which is probably only dependent on these bacteria.”
It would be “very interesting,” as a “proof-of-concept” study, to look at whether depleting Demodex would also delete S. alvi, he suggested.
The study was funded by Galderma. Dr. Homey has acted as a consultant, speaker or investigator for many pharmaceutical companies including Galderma.
A version of this article first appeared on Medscape.com.
, according to a report presented at the recent European Academy of Dermatology and Venereology (EADV) 2023 Congress.
“This is the first hint that the host’s cutaneous microbiome plays a secondary role in the immunopathogenesis of rosacea,” said Bernard Homey, MD, director of the department of dermatology at University Hospital Düsseldorf in Germany.
“In rosacea, we are well aware of trigger factors such as stress, UV light, heat, cold, food, and alcohol,” he said. “We are also well aware that there is an increase in Demodex mites in the pilosebaceous unit.”
Research over the past decade has also started to look at the potential role of the skin microbiome in the disease process, but answers have remained “largely elusive,” Dr. Homey said.
Ivermectin helps, but how?
Ivermectin 1% cream (Soolantra) has been approved by the U.S. Food and Drug Administration since 2014 for the treatment of the inflammatory lesions that are characteristic of rosacea, but its mechanism of action is not clear.
Dr. Homey presented the results of a study of 61 patients designed to look at how ivermectin might be working in the treatment of people with rosacea and investigate if there was any relation to the skin microbiome and transcriptome of patients.
The trial included 41 individuals with papulopustular rosacea and 20 individuals who did not have rosacea. For all patients, surface skin biopsies were performed twice 30 days apart using cyanoacrylate glue; patients with rosacea were treated with topical ivermectin 1% between biopsies. Skin samples obtained at day 0 and day 30 were examined under the microscope, and Demodex counts (mites/cm2) of skin and RNA sequencing of the cutaneous microbiome were undertaken.
The mean age of the patients with rosacea was 54.9 years, and the mean Demodex counts before and after treatment were a respective 7.2 cm2 and 0.9 cm2.
Using the Investigator’s General Assessment to assess the severity of rosacea, Homey reported that 43.9% of patients with rosacea had a decrease in scores at day 30, indicating improvement.
In addition, topical ivermectin resulted in a marked or total decrease in Demodex mite density for 87.5% of patients (n = 24) who were identified as having the mites.
Skin microbiome changes seen
As a form of quality control, skin microbiome changes among the patients were compared with control patients using 16S rRNA sequencing.
“The taxa we find within the cutaneous niche of inflammatory lesions of rosacea patients are significantly different from healthy volunteers,” Dr. Homey said.
Cutibacterium species are predominant in healthy control persons but are not present when there is inflammation in patients with rosacea. Instead, staphylococcus species “take over the niche, similar to atopic dermatitis,” he noted.
Looking at how treatment with ivermectin influences the organisms, the decrease in C. acnes seen in patients with rosacea persisted despite treatment, and the abundance of Staphylococcus epidermidis, S. hominis, and S. capitis increased further. This suggests a possible protective or homeostatic role of C. acnes but a pathogenic role for staphylococci, explained Dr. Homey.
“Surprisingly, although inflammatory lesions decrease, patients get better, the cutaneous microbiome does not revert to homeostatic conditions during topical ivermectin treatment,” he observed.
There is, of course, variability among individuals.
Dr. Homey also reported that Snodgrassella alvi – a microorganism believed to reside in the gut of Demodex folliculorum mites – was found in the skin microbiome of patients with rosacea before but not after ivermectin treatment. This may mean that this microorganism could be partially triggering inflammation in rosacea patients.
Looking at the transcriptome of patients, Dr. Homey said that there was downregulation of distinct genes that might make for more favorable conditions for Demodex mites.
Moreover, insufficient upregulation of interleukin-17 pathways might be working together with barrier defects in the skin and metabolic changes to “pave the way” for colonization by S. epidermidis.
Pulling it together
Dr. Homey and associates conclude in their abstract that the findings “support that rosacea lesions are associated with dysbiosis.”
Although treatment with ivermectin did not normalize the skin’s microbiome, it was associated with a decrease in Demodex mite density and the reduction of microbes associated with Demodex.
Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra in Portugal, who cochaired the late-breaking news session where the data were presented, asked whether healthy and affected skin in patients with rosacea had been compared, rather than comparing the skin of rosacea lesions with healthy control samples.
“No, we did not this, as this is methodologically a little bit more difficult,” Dr. Homey responded.
Also cochairing the session was Michel Gilliet, MD, chair of the department of dermatology at the University Hospital CHUV in Lausanne, Switzerland. He commented that these “data suggest that there’s an intimate link between Demodex and the skin microbiota and dysbiosis in in rosacea.”
Dr. Gilliet added: “You have a whole dysbiosis going on in rosacea, which is probably only dependent on these bacteria.”
It would be “very interesting,” as a “proof-of-concept” study, to look at whether depleting Demodex would also delete S. alvi, he suggested.
The study was funded by Galderma. Dr. Homey has acted as a consultant, speaker or investigator for many pharmaceutical companies including Galderma.
A version of this article first appeared on Medscape.com.
FROM EADV 2023
The Growing Pains of Changing Times for Acne and Rosacea Pathophysiology: Where Will It All End Up?
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
