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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Sustained jawline definition from hyaluronic gel, study reports
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Different variants may cause different long COVID symptoms: Study
Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.
The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.
Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”
However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment.
“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.
Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.
When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common.
Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).
The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
‘The take-home point’
Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.
Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”
Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”
Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”
Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”
Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.
“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
Study details
The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.
All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
Newer variants being studied
Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.
When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”
Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.
“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.
Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.”
Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.
“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.
Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.
Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).
A version of this article first appeared on Medscape.com.
Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.
The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.
Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”
However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment.
“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.
Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.
When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common.
Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).
The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
‘The take-home point’
Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.
Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”
Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”
Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”
Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”
Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.
“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
Study details
The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.
All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
Newer variants being studied
Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.
When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”
Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.
“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.
Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.”
Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.
“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.
Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.
Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).
A version of this article first appeared on Medscape.com.
Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.
The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.
Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”
However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment.
“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.
Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.
When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common.
Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).
The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
‘The take-home point’
Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.
Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”
Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”
Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”
Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”
Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.
“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
Study details
The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.
All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
Newer variants being studied
Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.
When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”
Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.
“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.
Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.”
Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.
“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.
Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.
Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).
A version of this article first appeared on Medscape.com.
CROI 2022
New trial data show hair growth in more alopecia areata patients
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
AT AAD 2022
Coffee drinking may cut heart disease risk, prolong survival
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
A trio of analyses based on the prospective UK Biobank cohort suggest that regular coffee drinking, especially a daily intake of two to three cups, is not only safe for the heart but may be cardioprotective.
People without cardiovascular disease with that level of coffee intake, compared with those who weren’t coffee drinkers, showed significantly reduced risks of death and a range of CVD endpoints, the reductions ranging from 8% to 15% over about 10 years.
In a separate analysis, participants with CVD at baseline also showed significantly improved survival with coffee intake of two to three cups daily, and no increased risk of arrhythmias.
In a third cut of the UK Biobank data, the clinical benefits of the same level of coffee drinking were observed whether the coffee consumed was the “instant” kind for reconstitution with water or brewed from ground whole beans.
Some clinicians advise their patients that coffee drinking may trigger or worsen some types of heart disease, observed Peter M. Kistler, MD, the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne. But the current analyses suggest that “daily coffee intake should not be discouraged, but rather considered part of a healthy diet.”
Dr. Kistler and colleagues are slated to present the three UK Biobank cohort analyses separately at the annual scientific sessions of the American College of Cardiology. He presented some of the data and commented on them at a press conference held in advance of the meeting.
UK Biobank study participants, who were on average in their late 50s, reported their level of daily coffee intake and preferred type of coffee on questionnaires. The researchers observed generally U-shaped relationships between daily number of cups of coffee and incident CVD, heart failure, coronary heart disease (CHD), stroke, atrial fibrillation, any arrhythmia, and death over 10 years.
“This is music to I think many of our patients’ ears, as well as many in the field of cardiology, as those of us that wake up early and stay up late in the hospital consume a fair amount of coffee,” observed Katie Berlacher, MD, associate chief of cardiology education at the University of Pittsburgh Medical Center.
The analyses were based on a large cohort and saw a consistent pattern for several cardiovascular outcomes, observed Dr. Berlacher, incoming ACC scientific session vice chair.
The findings could have a “profound impact in daily clinical care, as many of us caution patients who have or are at risk for having CV[D] against coffee consumption,” she told this news organization by email.
“These studies suggest that we do not have objective evidence to caution nor ask patients to stop drinking coffee, including patients who have arrhythmias.”
But importantly, “these studies are not causal,” she added. “So we cannot go so far as to recommend coffee consumption, though one could posit that randomized prospective studies should be done to elucidate causation.”
Coffee, Dr. Kistler observed, “is the most common cognitive enhancer. It wakes you up, makes you mentally sharper, and it’s a very important component of many people’s daily lives. The take-home message is that clinicians should NOT advise patients to stop drinking coffee up to three cups per day.”
Also, “in non–coffee drinkers, we do not have the data to suggest they should start drinking coffee,” he said. Moreover, people shouldn’t necessarily increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.
Benefits with or without known heart disease
The researchers identified 382,535 participants in the UK Biobank cohort who were free of CVD at baseline. Their median age was 57, and 52% were women.
Those who reported regular daily intake of two to three cups of coffee, compared with those who were not coffee drinkers, showed significantly reduced risks of CVD (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94), CHD (HR, 0.90; 95% CI, 0.87-0.93), heart failure (HR, 0.85; 95% CI, 0.81-0.90), arrhythmias (HR, 0.92; 95% CI, 0.88-0.95), and death from any cause over 10 years (HR, 0.86; 95% CI, 0.83-0.90) (P < .01 for all endpoints).
The risk of CVD death hit its lowest point at an intake of one cup per day (HR, 0.83; 95% CI, 0.75-0.93). The risk of stroke was lowest at less than one cup per day (HR, 0.85; 95% CI, 0.75-0.96).
A separate analysis found similar outcomes among a different subset of UK Biobank participants with recognized CVD at baseline. Among 34,279 such persons, those who drank two to three cups of coffee per day, compared with non–coffee drinkers, showed a reduced risk of death over 10 years (HR, 0.92; 95% CI, 0.86-0.99; P = .03).
Among the 24,111 persons diagnosed with arrhythmias at baseline, the lowest mortality risk was observed at one cup per day (HR, 0.85; 95% CI, 0.78-0.94; P < .01). Among those with atrial fibrillation or atrial flutter, one cup per day was associated with a mortality HR of 0.82 (95% CI, 0.73-0.93; P < .01).
In still another analysis of UK Biobank cohort, incident CVD and mortality during the 10-year follow-up was similarly reduced among participants who reported consumption of brewed ground coffee and, separately, instant coffee, compared with non–coffee drinkers. Decaffeinated coffee showed a mostly neutral or inconsistent effect on the clinical endpoints.
The lowest CVD risk was observed at two to three cups per day among those regularly drinking ground coffee (HR, 0.83; 95% CI, 0.79-0.87) and those predominantly taking instant coffee (HR, 0.91; 95% CI, 0.88-0.95).
Potential mechanisms, study limitations
“Caffeine blocks adenosine receptors, which may explain its potential mild antiarrhythmic properties,” Dr. Kistler said. “Regular coffee drinkers with supraventricular tachycardia coming to the emergency department often need higher adenosine doses to revert.”
Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate, Dr. Kistler added, and coffee has been associated with a significantly reduced risk of new-onset type 2 diabetes.
However, coffee beans contain more than 100 biologically active compounds, he noted. They include antioxidant polyphenols that reduce oxidative stress and modulate metabolism. Better survival with habitual coffee consumption may be related to improved endothelial function, circulating antioxidants, improved insulin sensitivity, or reduced inflammation, the researchers noted.
They acknowledged some limitations to the analyses. Cause and effect can’t be determined from the observational data. Also, a cup of coffee in the United Kingdom means about 200-250 mL of brew, but its actual caffeine content can vary from 90 mg to 250 mg. Also, data regarding added sugar or milk was lacking. And UK Biobank participants are predominantly White, so the findings may not be generalizable to other populations.
A version of this article first appeared on Medscape.com.
FROM ACC 2022
Novel isotretinoin ointment for congenital ichthyosis shows promise
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
AT AAD 2022
Aluminum named allergen of the year
BOSTON – The . Aluminum salts, which are the major cause of allergic reactions, are “ubiquitous,” Donald Belsito, MD, professor of dermatology at Columbia University, New York, said at the annual meeting of the American Contact Dermatitis Society.
These salts can be found in sunscreen, cosmetics, dental restorations, and food, to name a few, though the most commonly identified reactions are from aluminum hydroxide, which can be found in some vaccines or preparations for allergen-specific immunotherapy. “It’s the aluminum hydroxide that seems to be more allergenic than other aluminum salts,” Dr. Belsito said in an interview.
“It’s not a dangerous allergy; It’s not a threat,” he said, “but it’s something that dermatologists need to be aware of.”
These reactions normally present as itchy nodules that can last for months and even years, like some reactions from patch testing. “We’re not talking about a vaccine allergy in such a way where people are getting anaphylaxis,” JiaDe Yu, MD, a pediatric dermatologist specializing in allergic contact dermatitis at Massachusetts General Hospital, Boston, said in an interview. “An itchy rash is what we tend to see.”
There have also been occasional reports of atopic dermatitis from aluminum in antiperspirants, astringents, as well as from the metallic aluminum.
Dr. Yu noted that aluminum allergies are not thought to be very common, but the overall prevalence is not known. Studies do suggest, however, that the allergy may be more prevalent in children. In one recent study in Sweden, 5% of children and 0.9% of adults who underwent patch testing had an aluminum contact allergy.
Recommendations for testing
Aluminum is not included in baseline patch testing in the United States, though a recent report about the allergen in the journal Dermatitis argued for its inclusion for pediatric patch testing. Both Dr. Belsito and Dr. Yu agreed that the best approach is to do targeted testing. “If there is a suspicion for it, absolutely test for it,” Dr. Yu said, but if a patient comes in with something like eyelid dermatitis or a rash after a hair care appointment, an aluminum allergy is not very likely.
Because aluminum is also present in Finn Chambers for patch testing, Dr. Belsito advised using plastic chambers in people suspected of having an aluminum allergy. He now uses only plastic chambers in children, he said, as some patients have had reactions to the Finn Chambers even if they have no history of reactions to vaccines or other aluminum-containing products.
While aluminum chloride hexahydrate (ACH) 2% in petrolatum is the commercially available preparation in patch testing, a preparation with ACH 10% is more sensitive, Dr. Belsito said. If a physician strongly suspects an aluminum allergy in a patient but the test with the ACH 2% is negative, he or she should then try a 10% solution, he noted, adding that 7-day readings are also necessary to maximize accuracy.
Vaccine safety
One of the concerns about naming aluminum as the allergen of the year is the potential to cause anxiety around vaccines. “We want to make sure that we’re not giving more fuel to people who have an excuse not to get a vaccine,” Dr. Yu said. “We certainly want to reinforce that fact that it is safe.” Dr. Belsito noted that COVID-19 vaccines do not contain aluminum.
Even on the rare chance that a patient does have a reaction to an aluminum-containing vaccine, these subcutaneous nodules resolve over time, Dr. Belsito said. In his own clinical experience, “99.99% of the time they resolve and there is no residual.” He did add that overreacting to the rash by prescribing injectable steroids can lead to steroid atrophy. In these cases, a topical steroid may be more appropriate.
All unexpected or clinically significant vaccine reactions should be reported to the Vaccine Adverse Event Reporting System, cosponsored by the Centers for Disease Control and Prevention and the Food and Drug Administration. The Clinical Immunization Project Safety Assessment Project, from the CDC, also can provide expertise and advice on aluminum-free alternatives for some vaccines.
Dr. Belsito and Dr. Yu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The . Aluminum salts, which are the major cause of allergic reactions, are “ubiquitous,” Donald Belsito, MD, professor of dermatology at Columbia University, New York, said at the annual meeting of the American Contact Dermatitis Society.
These salts can be found in sunscreen, cosmetics, dental restorations, and food, to name a few, though the most commonly identified reactions are from aluminum hydroxide, which can be found in some vaccines or preparations for allergen-specific immunotherapy. “It’s the aluminum hydroxide that seems to be more allergenic than other aluminum salts,” Dr. Belsito said in an interview.
“It’s not a dangerous allergy; It’s not a threat,” he said, “but it’s something that dermatologists need to be aware of.”
These reactions normally present as itchy nodules that can last for months and even years, like some reactions from patch testing. “We’re not talking about a vaccine allergy in such a way where people are getting anaphylaxis,” JiaDe Yu, MD, a pediatric dermatologist specializing in allergic contact dermatitis at Massachusetts General Hospital, Boston, said in an interview. “An itchy rash is what we tend to see.”
There have also been occasional reports of atopic dermatitis from aluminum in antiperspirants, astringents, as well as from the metallic aluminum.
Dr. Yu noted that aluminum allergies are not thought to be very common, but the overall prevalence is not known. Studies do suggest, however, that the allergy may be more prevalent in children. In one recent study in Sweden, 5% of children and 0.9% of adults who underwent patch testing had an aluminum contact allergy.
Recommendations for testing
Aluminum is not included in baseline patch testing in the United States, though a recent report about the allergen in the journal Dermatitis argued for its inclusion for pediatric patch testing. Both Dr. Belsito and Dr. Yu agreed that the best approach is to do targeted testing. “If there is a suspicion for it, absolutely test for it,” Dr. Yu said, but if a patient comes in with something like eyelid dermatitis or a rash after a hair care appointment, an aluminum allergy is not very likely.
Because aluminum is also present in Finn Chambers for patch testing, Dr. Belsito advised using plastic chambers in people suspected of having an aluminum allergy. He now uses only plastic chambers in children, he said, as some patients have had reactions to the Finn Chambers even if they have no history of reactions to vaccines or other aluminum-containing products.
While aluminum chloride hexahydrate (ACH) 2% in petrolatum is the commercially available preparation in patch testing, a preparation with ACH 10% is more sensitive, Dr. Belsito said. If a physician strongly suspects an aluminum allergy in a patient but the test with the ACH 2% is negative, he or she should then try a 10% solution, he noted, adding that 7-day readings are also necessary to maximize accuracy.
Vaccine safety
One of the concerns about naming aluminum as the allergen of the year is the potential to cause anxiety around vaccines. “We want to make sure that we’re not giving more fuel to people who have an excuse not to get a vaccine,” Dr. Yu said. “We certainly want to reinforce that fact that it is safe.” Dr. Belsito noted that COVID-19 vaccines do not contain aluminum.
Even on the rare chance that a patient does have a reaction to an aluminum-containing vaccine, these subcutaneous nodules resolve over time, Dr. Belsito said. In his own clinical experience, “99.99% of the time they resolve and there is no residual.” He did add that overreacting to the rash by prescribing injectable steroids can lead to steroid atrophy. In these cases, a topical steroid may be more appropriate.
All unexpected or clinically significant vaccine reactions should be reported to the Vaccine Adverse Event Reporting System, cosponsored by the Centers for Disease Control and Prevention and the Food and Drug Administration. The Clinical Immunization Project Safety Assessment Project, from the CDC, also can provide expertise and advice on aluminum-free alternatives for some vaccines.
Dr. Belsito and Dr. Yu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The . Aluminum salts, which are the major cause of allergic reactions, are “ubiquitous,” Donald Belsito, MD, professor of dermatology at Columbia University, New York, said at the annual meeting of the American Contact Dermatitis Society.
These salts can be found in sunscreen, cosmetics, dental restorations, and food, to name a few, though the most commonly identified reactions are from aluminum hydroxide, which can be found in some vaccines or preparations for allergen-specific immunotherapy. “It’s the aluminum hydroxide that seems to be more allergenic than other aluminum salts,” Dr. Belsito said in an interview.
“It’s not a dangerous allergy; It’s not a threat,” he said, “but it’s something that dermatologists need to be aware of.”
These reactions normally present as itchy nodules that can last for months and even years, like some reactions from patch testing. “We’re not talking about a vaccine allergy in such a way where people are getting anaphylaxis,” JiaDe Yu, MD, a pediatric dermatologist specializing in allergic contact dermatitis at Massachusetts General Hospital, Boston, said in an interview. “An itchy rash is what we tend to see.”
There have also been occasional reports of atopic dermatitis from aluminum in antiperspirants, astringents, as well as from the metallic aluminum.
Dr. Yu noted that aluminum allergies are not thought to be very common, but the overall prevalence is not known. Studies do suggest, however, that the allergy may be more prevalent in children. In one recent study in Sweden, 5% of children and 0.9% of adults who underwent patch testing had an aluminum contact allergy.
Recommendations for testing
Aluminum is not included in baseline patch testing in the United States, though a recent report about the allergen in the journal Dermatitis argued for its inclusion for pediatric patch testing. Both Dr. Belsito and Dr. Yu agreed that the best approach is to do targeted testing. “If there is a suspicion for it, absolutely test for it,” Dr. Yu said, but if a patient comes in with something like eyelid dermatitis or a rash after a hair care appointment, an aluminum allergy is not very likely.
Because aluminum is also present in Finn Chambers for patch testing, Dr. Belsito advised using plastic chambers in people suspected of having an aluminum allergy. He now uses only plastic chambers in children, he said, as some patients have had reactions to the Finn Chambers even if they have no history of reactions to vaccines or other aluminum-containing products.
While aluminum chloride hexahydrate (ACH) 2% in petrolatum is the commercially available preparation in patch testing, a preparation with ACH 10% is more sensitive, Dr. Belsito said. If a physician strongly suspects an aluminum allergy in a patient but the test with the ACH 2% is negative, he or she should then try a 10% solution, he noted, adding that 7-day readings are also necessary to maximize accuracy.
Vaccine safety
One of the concerns about naming aluminum as the allergen of the year is the potential to cause anxiety around vaccines. “We want to make sure that we’re not giving more fuel to people who have an excuse not to get a vaccine,” Dr. Yu said. “We certainly want to reinforce that fact that it is safe.” Dr. Belsito noted that COVID-19 vaccines do not contain aluminum.
Even on the rare chance that a patient does have a reaction to an aluminum-containing vaccine, these subcutaneous nodules resolve over time, Dr. Belsito said. In his own clinical experience, “99.99% of the time they resolve and there is no residual.” He did add that overreacting to the rash by prescribing injectable steroids can lead to steroid atrophy. In these cases, a topical steroid may be more appropriate.
All unexpected or clinically significant vaccine reactions should be reported to the Vaccine Adverse Event Reporting System, cosponsored by the Centers for Disease Control and Prevention and the Food and Drug Administration. The Clinical Immunization Project Safety Assessment Project, from the CDC, also can provide expertise and advice on aluminum-free alternatives for some vaccines.
Dr. Belsito and Dr. Yu have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACDS 2022
COVID-19 infection linked to risk of cutaneous autoimmune and vascular diseases
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
AT AAD 2022
Platelet-rich plasma for hair regrowth requires art and science
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2022
‘Extensive’ evidence for altered brain-gut-microbiome system in IBS
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
FROM GMFH 2022
Topical options for treating melasma continue to expand
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
AT AAD 2022