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All’s Well That Ends Swell(ing)
ANSWER
The correct answer is elephantiasis nostras verrucosa (ENV; choice “d”).
DISCUSSION
ENV is a rare condition of advanced cutaneous hypertrophy secondary to a combination of contributing factors including: a sedentary lifestyle, obesity, chronic venous stasis, repeated bouts of lymphangitis, cellulitis, and congestive heart failure (CHF). Most commonly affecting the lower extremities, it is occasionally seen in other dependent areas such as the scrotum and the abdominal pannus. It is, essentially, an exaggerated form of cutaneous lymphedema that causes the skin to become increasingly thick and fibrotic, changes which also reduce blood flow to or from the area.
Despite its name, ENV is not associated with elephantiasis, more commonly known as lymphatic filariasis (choice “b”). Although that condition manifests with similar skin changes, it is typically seen only in those who live in tropical areas where these organisms are endemic—places this patient has never visited.
There was no reason to believe that these skin changes were attributable to warts (choice “a”). Biopsy would have settled that question but also would have run the risk of creating a nonhealing wound, which could easily turn into an ulcer.
Lymphedema (choice “c”) was clearly present, but it was quite advanced—far beyond what is usually seen in venous insufficiency. This diagnosis would not, by itself, explain the nodules or extreme fibrosis.
Other potential causes for these skin changes include postradiation and pretibial myxedema, which had been ruled out prior to the dermatology consult.
TREATMENT
As with simple venous insufficiency, treatment of ENV consists of compression, elevation, and weight loss. For this patient, the diuretics prescribed as part of her CHF treatment might help a bit, but her prognosis is guarded at best.
ANSWER
The correct answer is elephantiasis nostras verrucosa (ENV; choice “d”).
DISCUSSION
ENV is a rare condition of advanced cutaneous hypertrophy secondary to a combination of contributing factors including: a sedentary lifestyle, obesity, chronic venous stasis, repeated bouts of lymphangitis, cellulitis, and congestive heart failure (CHF). Most commonly affecting the lower extremities, it is occasionally seen in other dependent areas such as the scrotum and the abdominal pannus. It is, essentially, an exaggerated form of cutaneous lymphedema that causes the skin to become increasingly thick and fibrotic, changes which also reduce blood flow to or from the area.
Despite its name, ENV is not associated with elephantiasis, more commonly known as lymphatic filariasis (choice “b”). Although that condition manifests with similar skin changes, it is typically seen only in those who live in tropical areas where these organisms are endemic—places this patient has never visited.
There was no reason to believe that these skin changes were attributable to warts (choice “a”). Biopsy would have settled that question but also would have run the risk of creating a nonhealing wound, which could easily turn into an ulcer.
Lymphedema (choice “c”) was clearly present, but it was quite advanced—far beyond what is usually seen in venous insufficiency. This diagnosis would not, by itself, explain the nodules or extreme fibrosis.
Other potential causes for these skin changes include postradiation and pretibial myxedema, which had been ruled out prior to the dermatology consult.
TREATMENT
As with simple venous insufficiency, treatment of ENV consists of compression, elevation, and weight loss. For this patient, the diuretics prescribed as part of her CHF treatment might help a bit, but her prognosis is guarded at best.
ANSWER
The correct answer is elephantiasis nostras verrucosa (ENV; choice “d”).
DISCUSSION
ENV is a rare condition of advanced cutaneous hypertrophy secondary to a combination of contributing factors including: a sedentary lifestyle, obesity, chronic venous stasis, repeated bouts of lymphangitis, cellulitis, and congestive heart failure (CHF). Most commonly affecting the lower extremities, it is occasionally seen in other dependent areas such as the scrotum and the abdominal pannus. It is, essentially, an exaggerated form of cutaneous lymphedema that causes the skin to become increasingly thick and fibrotic, changes which also reduce blood flow to or from the area.
Despite its name, ENV is not associated with elephantiasis, more commonly known as lymphatic filariasis (choice “b”). Although that condition manifests with similar skin changes, it is typically seen only in those who live in tropical areas where these organisms are endemic—places this patient has never visited.
There was no reason to believe that these skin changes were attributable to warts (choice “a”). Biopsy would have settled that question but also would have run the risk of creating a nonhealing wound, which could easily turn into an ulcer.
Lymphedema (choice “c”) was clearly present, but it was quite advanced—far beyond what is usually seen in venous insufficiency. This diagnosis would not, by itself, explain the nodules or extreme fibrosis.
Other potential causes for these skin changes include postradiation and pretibial myxedema, which had been ruled out prior to the dermatology consult.
TREATMENT
As with simple venous insufficiency, treatment of ENV consists of compression, elevation, and weight loss. For this patient, the diuretics prescribed as part of her CHF treatment might help a bit, but her prognosis is guarded at best.
A 61-year-old black woman presents for worrisome skin changes on her lower extremities. She reports that the condition is generally uncomfortable, but during occasional flares, it causes serious pain. She’s been affected for “many years” without diagnosis or resolution. It was her new primary care provider who, after seeing the lesions, sent her to dermatology.
The patient’s medical history includes diabetes, congestive heart failure, and obesity. All are being managed reasonably well.
Examination, performed while she is in a recumbent position, reveals legs swollen out of proportion to the rest of her body. Little or no erythema is noted. Both legs are affected equally, but only from just below the knees down to and including the feet. These areas, including her feet, are quite swollen, though no pitting edema can be provoked. The skin is quite firm and studded with multiple discrete and confluent 1-2 cm firm nodules. The skin around her ankles feels almost “woody” to the touch. There is no tenderness or increased warmth on palpation, nor is any drainage noted. (She also has a dystrophic great toenail that was partially avulsed by recent trauma.)
Benzene was found in some sunscreens. Now what?
Just before Memorial Day, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.
“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”
In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”
The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.
Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.
“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”
When asked to comment on Valisure’s findings, an FDA spokesperson said, “The FDA takes seriously any safety concerns raised about products we regulate, including sunscreen. While the agency evaluates the submitted citizen petition, we will continue to monitor the sunscreen marketplace and manufacturing efforts to help ensure the availability of safe sunscreens for U.S. consumers.”
Both Johnson & Johnson, Neutrogena’s parent company, and Banana Boat issued statements reiterating that benzene is not an ingredient in their products.
Assessing the risks
There is a risk of patients taking away the wrong message from these findings.
“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.
On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.
“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”
And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.
Advising patients
With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.
“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”
Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”
As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
Just before Memorial Day, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.
“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”
In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”
The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.
Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.
“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”
When asked to comment on Valisure’s findings, an FDA spokesperson said, “The FDA takes seriously any safety concerns raised about products we regulate, including sunscreen. While the agency evaluates the submitted citizen petition, we will continue to monitor the sunscreen marketplace and manufacturing efforts to help ensure the availability of safe sunscreens for U.S. consumers.”
Both Johnson & Johnson, Neutrogena’s parent company, and Banana Boat issued statements reiterating that benzene is not an ingredient in their products.
Assessing the risks
There is a risk of patients taking away the wrong message from these findings.
“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.
On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.
“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”
And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.
Advising patients
With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.
“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”
Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”
As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
Just before Memorial Day, which include batches from Neutrogena, Banana Boat, CVS Health, and other brands. More than three-quarters of the products are sprays.
“We’re asking our patients to put sunscreen on from 6 months of age, telling them to do it their entire life, their whole body, multiple times a day,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in an interview. If benzene-contaminated sunscreen proves to be a widespread problem, he said, “the benzene amounts can add up to a significant chronic exposure over a lifetime.”
In the Valisure statement announcing the findings, Dr. Bunick, who is also quoted in the petition, said that “it is critical that regulatory agencies address benzene contamination in sunscreens, and all topical medications at the manufacturing and final product level, so that all individuals feel safe using sunscreen products.”
The list of products that tested positive is included in the citizen petition, and a full list of products that did not show any contamination is available in an attachment.
Benzene is not an ingredient in sunscreen, and Valisure’s petition suggests that the findings are a result of contamination somewhere in the manufacturing process, not of product degradation.
“This isn’t a sunscreen issue, it’s a manufacturing issue,” said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington. “We don’t want those things to be blurred.”
When asked to comment on Valisure’s findings, an FDA spokesperson said, “The FDA takes seriously any safety concerns raised about products we regulate, including sunscreen. While the agency evaluates the submitted citizen petition, we will continue to monitor the sunscreen marketplace and manufacturing efforts to help ensure the availability of safe sunscreens for U.S. consumers.”
Both Johnson & Johnson, Neutrogena’s parent company, and Banana Boat issued statements reiterating that benzene is not an ingredient in their products.
Assessing the risks
There is a risk of patients taking away the wrong message from these findings.
“People already have ambivalence about sunscreen, and this is just going to make that worse,” Dr. Friedman said in an interview. He pointed out that benzene is present in car exhaust, second-hand smoke, and elsewhere. Inhalation exposure has been the primary focus of toxicology investigations, as has exposure from ingesting things such as contaminated drinking water – not via topical application. “We don’t know how effectively [benzene] gets through the skin, if it gets absorbed systemically, and how that then behaves downstream,” he noted.
On the other hand, ultraviolet radiation is a well-established carcinogen. Avoiding an effective preventive measure such as sunscreen could prove more harmful than exposure to trace amounts of benzene, ultimately to be determined by the FDA.
“Just because those particular products do pose a risk, that doesn’t erase the message that sunscreens are safe and should be used,” Dr. Bunick said. “It’s not mutually exclusive.”
And then there’s the fact that the benzene contamination appears to be fairly limited. “The majority of products we tested, over 200 of them, had no detectable amounts of benzene, and uncontaminated sunscreen should certainly continue to be used,” David Light, CEO of Valisure, told this news organization.
Advising patients
With headlines blaring the news about a carcinogen in sunscreen, patients will be reaching out for advice.
“The number one question patients will have is, ‘What sunscreen do you recommend?’” said Dr. Bunick. “The answer should be to pick a sunscreen that we know wasn’t contaminated. Reassure your patient the ingredients themselves are effective and safe, and that’s not what’s leading to the contamination.”
Dr. Friedman agrees. “We need to be mindful. Dermatologists need to be armed with the facts in order to counsel patients: Sunscreen is still a very important, effective, and safe, scientifically based way to prevent the harmful effects of the sun, in addition to things like sun protective clothing and seeking shade between 10 a.m. and 4 p.m.”
As alarming as Valisure’s findings may seem initially, Dr. Bunick noted a silver lining. “The consumer, the public should feel reassured this report is out there. It shows that someone’s watching out. That’s an important safety message: These things aren’t going undetected.”
Erythematous axillary plaques
Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.
Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.
Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.
Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.1 Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733
Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.
Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.
Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.
Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.1 Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.
Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.
Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.
Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.1 Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733
Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733
Pediatric Dermatology 2021 Supplement
Pediatric Dermatology: A Supplement to Pediatric News & Dermatology News
- Dupilumab curbed itch intensity, frequency in children with severe eczema
- Vitiligo treatment options abound but consider patient goals
- Beware a pair of dermatologic emergencies in children
- Database offers snapshot of common causes of pediatric allergic contact dermatitis
- Who’s at risk for depression on isotretinoin?
- Expert shares his approach to treating warts in children
Pediatric Dermatology: A Supplement to Pediatric News & Dermatology News
- Dupilumab curbed itch intensity, frequency in children with severe eczema
- Vitiligo treatment options abound but consider patient goals
- Beware a pair of dermatologic emergencies in children
- Database offers snapshot of common causes of pediatric allergic contact dermatitis
- Who’s at risk for depression on isotretinoin?
- Expert shares his approach to treating warts in children
Pediatric Dermatology: A Supplement to Pediatric News & Dermatology News
- Dupilumab curbed itch intensity, frequency in children with severe eczema
- Vitiligo treatment options abound but consider patient goals
- Beware a pair of dermatologic emergencies in children
- Database offers snapshot of common causes of pediatric allergic contact dermatitis
- Who’s at risk for depression on isotretinoin?
- Expert shares his approach to treating warts in children
GRAPPA refines recommendations on psoriatic disease treatment
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.
“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.
“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).
“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.
The last version of the guidelines was developed in 2015 and published in 2016, and since then there have been new data on Janus kinase inhibitors and interleukin-23 inhibitors, for example, which have now been incorporated into the updated recommendations alongside the old stalwarts of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors.
“I think that we can see some similarities but also differences compared to the previous version of the recommendations,” Dr. Gossec said.
One similarity is that the recommendations retain their modular or domain-oriented approach, keeping the core way that clinicians can use the recommendations based on their patients’ presentations. So, they still cover the management of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease individually.
What’s different, however, is that the domain on comorbidities has been split into two to cover general comorbidities and to give more specific guidance on managing inflammatory bowel disease (IBD) and uveitis, “both of which may not ‘strictly speaking’ be treated by rheumatologists or dermatologists, but are manifestations which can appear in psoriatic disease,” Dr. Gossec noted.
IBD and uveitis “are part of the whole spondyloarthritis syndrome and are genetically related,” Dr. Coates said in her interview. “A lot of the drugs have licenses in those particular areas. The evidence is much stronger for which medication you should choose if somebody has psoriatic arthritis and Crohn’s disease or psoriatic arthritis and uveitis,” she noted.
When it comes to the rest of the comorbidities, think “cardiovascular disease, liver disease, infections – all the ‘normal’ comorbidities,” she added, noting “that’s usually where there’s a lot less data” on which drug to use.
New overarching principle and position statements
The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.
To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.
There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”
The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.
Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”
The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”
GRAPPA intentionally gives clinicians more freedom
While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”
One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.
“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.
What’s next?
There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.
Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.
“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.
Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”
He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”
GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.
Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.
Dr. Studenic had nothing to disclose.
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.
“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.
“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).
“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.
The last version of the guidelines was developed in 2015 and published in 2016, and since then there have been new data on Janus kinase inhibitors and interleukin-23 inhibitors, for example, which have now been incorporated into the updated recommendations alongside the old stalwarts of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors.
“I think that we can see some similarities but also differences compared to the previous version of the recommendations,” Dr. Gossec said.
One similarity is that the recommendations retain their modular or domain-oriented approach, keeping the core way that clinicians can use the recommendations based on their patients’ presentations. So, they still cover the management of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease individually.
What’s different, however, is that the domain on comorbidities has been split into two to cover general comorbidities and to give more specific guidance on managing inflammatory bowel disease (IBD) and uveitis, “both of which may not ‘strictly speaking’ be treated by rheumatologists or dermatologists, but are manifestations which can appear in psoriatic disease,” Dr. Gossec noted.
IBD and uveitis “are part of the whole spondyloarthritis syndrome and are genetically related,” Dr. Coates said in her interview. “A lot of the drugs have licenses in those particular areas. The evidence is much stronger for which medication you should choose if somebody has psoriatic arthritis and Crohn’s disease or psoriatic arthritis and uveitis,” she noted.
When it comes to the rest of the comorbidities, think “cardiovascular disease, liver disease, infections – all the ‘normal’ comorbidities,” she added, noting “that’s usually where there’s a lot less data” on which drug to use.
New overarching principle and position statements
The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.
To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.
There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”
The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.
Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”
The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”
GRAPPA intentionally gives clinicians more freedom
While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”
One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.
“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.
What’s next?
There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.
Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.
“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.
Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”
He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”
GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.
Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.
Dr. Studenic had nothing to disclose.
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.
“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.
“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).
“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.
The last version of the guidelines was developed in 2015 and published in 2016, and since then there have been new data on Janus kinase inhibitors and interleukin-23 inhibitors, for example, which have now been incorporated into the updated recommendations alongside the old stalwarts of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors.
“I think that we can see some similarities but also differences compared to the previous version of the recommendations,” Dr. Gossec said.
One similarity is that the recommendations retain their modular or domain-oriented approach, keeping the core way that clinicians can use the recommendations based on their patients’ presentations. So, they still cover the management of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease individually.
What’s different, however, is that the domain on comorbidities has been split into two to cover general comorbidities and to give more specific guidance on managing inflammatory bowel disease (IBD) and uveitis, “both of which may not ‘strictly speaking’ be treated by rheumatologists or dermatologists, but are manifestations which can appear in psoriatic disease,” Dr. Gossec noted.
IBD and uveitis “are part of the whole spondyloarthritis syndrome and are genetically related,” Dr. Coates said in her interview. “A lot of the drugs have licenses in those particular areas. The evidence is much stronger for which medication you should choose if somebody has psoriatic arthritis and Crohn’s disease or psoriatic arthritis and uveitis,” she noted.
When it comes to the rest of the comorbidities, think “cardiovascular disease, liver disease, infections – all the ‘normal’ comorbidities,” she added, noting “that’s usually where there’s a lot less data” on which drug to use.
New overarching principle and position statements
The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.
To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.
There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”
The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.
Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”
The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”
GRAPPA intentionally gives clinicians more freedom
While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”
One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.
“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.
What’s next?
There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.
Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.
“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.
Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”
He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”
GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.
Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.
Dr. Studenic had nothing to disclose.
FROM THE EULAR 2021 CONGRESS
Intravenous immunoglobulin controls dermatomyositis in phase 3 trial
Nearly 50% achieve moderate improvement or better
The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.
At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.
ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.
“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”
This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.
The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.
Multiple response criteria favor IVIg
In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.
The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).
At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.
The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.
At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
Benefit is significant for skin and muscle
Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.
“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.
The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.
Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).
Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.
Effect on associated conditions is planned
The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.
There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.
Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.
Nearly 50% achieve moderate improvement or better
Nearly 50% achieve moderate improvement or better
The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.
At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.
ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.
“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”
This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.
The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.
Multiple response criteria favor IVIg
In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.
The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).
At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.
The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.
At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
Benefit is significant for skin and muscle
Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.
“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.
The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.
Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).
Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.
Effect on associated conditions is planned
The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.
There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.
Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.
The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.
At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.
ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.
“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”
This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.
The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.
Multiple response criteria favor IVIg
In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.
The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).
At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.
The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.
At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).
Benefit is significant for skin and muscle
Changes in the two major components of dermatomyositis were tracked individually. For skin symptoms, patients were evaluated with the Cutaneous Dermatomyositis Disease Areas and Severity Index (CDASI). For muscle involvement, symptoms were evaluated with the 8-item Manual Muscle Testing (MMT-8) tool.
“The effects of IVIg on the muscle and the skin were both highly statistically significant,” Dr. Aggarwal reported. He said the CDASI score was reduced by almost half at the end of 16 weeks among those treated with IVIg relative to those treated with placebo. Improvement in MMT-8 scores were also clinically as well as statistically significant.
The IVIg therapy was well tolerated. The most common adverse effects in this study, like those reported with IVIg when used to treat other diseases, were headache, pyrexia, and nausea, but Dr. Aggarwal reported that these were generally mild.
Serious adverse events, particularly thromboembolism, did occur over the course of the study, but the rate of events was only slightly higher in the group receiving active therapy (5.8% vs. 4.2%).
Patients who entered the study were permitted to remain on most immunosuppressive therapies, such as methotrexate, mycophenolate, tacrolimus, and glucocorticoids. Dr. Aggarwal said that the majority of patients were taking a glucocorticoid and at least one nonglucocorticoid immunosuppressant.
Effect on associated conditions is planned
The data from this trial have not yet been analyzed for the impact of IVIg on conditions that occur frequently in association with dermatomyositis, such as interstitial lung disease (ILD) and dysphagia, but Dr. Aggarwal reported that there are plans to do so. Although severe ILD was a trial exclusion, the presence of mild to moderate ILD and dysphagia were evaluated at baseline, so the impact of treatment can be assessed.
There are also plans to evaluate how the presence or absence of myositis-specific antibodies, which were also evaluated at baseline, affected response to IVIg.
Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Dr. Schulze-Koops reported no relevant potential conflicts of interest.
FROM THE EULAR 2021 CONGRESS
Asymptomatic hyperpigmented skin changes
The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).
Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.1
At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.
The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.
Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.
Barros HR, de Almeida JRP, Mattos e Dinato SL, et al. Lichen planus pigmentosus inversus. An Bras Dermatol. 2013;88(6 suppl 1):146-149. doi:10.1590/abd1806-4841.20132599
The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).
Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.1
At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.
The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.
Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.
The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).
Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.1
At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.
The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.
Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.
Barros HR, de Almeida JRP, Mattos e Dinato SL, et al. Lichen planus pigmentosus inversus. An Bras Dermatol. 2013;88(6 suppl 1):146-149. doi:10.1590/abd1806-4841.20132599
Barros HR, de Almeida JRP, Mattos e Dinato SL, et al. Lichen planus pigmentosus inversus. An Bras Dermatol. 2013;88(6 suppl 1):146-149. doi:10.1590/abd1806-4841.20132599
FDA approves secukinumab in psoriasis patients age six and older
The who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.
Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.
The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”
The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.
At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.
Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.
The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.
“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”
Dr. Cordoro reported having no financial disclosures.
The who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.
Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.
The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”
The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.
At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.
Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.
The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.
“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”
Dr. Cordoro reported having no financial disclosures.
The who are candidates for systemic therapy or phototherapy. The expanded indication marks the first time the drug has been available for a pediatric population in the United States.
Children with plaque psoriasis are often undertreated because of fear of side effects of therapies, according to Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco. “Now, more and more medicines are being tested for safety and efficacy in children, and we no longer have to rely on adult studies to inform treatment choices for children,” Dr. Cordoro told this news organization.
The FDA approval of secukinumab for children aged 6 and older with moderate to severe psoriasis “is a welcome addition to the therapeutic toolbox for pediatric psoriasis,” she said. “We’ve entered an era where severe pediatric psoriasis has become a condition that can be adequately controlled with minimal risk and with the convenience of intermittent injections. This has changed the playing field for these children and their families completely. Given the potential short- and long-term negative impact of chronic inflammation on the body of a growing child, we now have approved treatments that can safely offset the risks of undertreated severe psoriasis on the functional and psychological health of the child.”
The approved pediatric dosing for secukinumab is 75 mg or 150 mg depending on the child’s weight at the time of dosing, and it is administered by subcutaneous injection every 4 weeks after an initial loading regimen. According to a press release from Novartis, the FDA approval came on the heels of two phase 3 studies that evaluated the use of secukinumab in children aged 6 to younger than 18 years with plaque psoriasis. The first was a 52-week, randomized, double-blind, placebo- and active-controlled study which included 162 children 6 years of age and older with severe plaque psoriasis. The doses evaluated were 75 mg for children who weighed less than 50 kg and 150 mg for those 50 kg or greater.
At week 12, the Psoriasis Area Severity Index (PASI)-75 response was 55% among children in the 75-mg dosing group vs. 10% in the placebo group and 86% in the 150-mg dosing group vs. 19% in the placebo group.
Meanwhile, the Investigator’s Global Assessment modified 2011 (IGA) “clear” response was achieved in 32% of children in the 75-mg dosing group vs. 5% in the placebo group and in 81% of children in the 150-mg dosing group vs. 5% in the placebo group. An IGA “almost clear” skin response was achieved in 81% of children in the 75-mg dosing group vs. 5% in the placebo group.
The second phase 3 study was a randomized open-label, 208-week trial of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis. According to the Novartis press release, the safety profile reported in both trials was consistent with the safety profile reported in adult plaque psoriasis trials and no new safety signals were observed. The updated prescribing information for secukinumab can be found here.
“When considering treatment with a systemic agent such as a biologic, it is important to consider objective measures of severity, such as extent of disease and involvement of joints but also subjective indicators of severity such as impact beyond the skin on psychological well-being,” Dr. Cordoro said in the interview. “Kids with psoriasis in visible locations may socially isolate themselves due to embarrassment or bullying. Therefore, the impact of moderate to severe psoriasis not only on overall health but on self-esteem and identity formation can be significant, and therefore adequately treating children of all ages to prevent the downstream negative consequences of childhood psoriasis is critical.”
Dr. Cordoro reported having no financial disclosures.
Benzene found in some sunscreen products, online pharmacy says
Valisure, an online pharmacy known for testing every batch of medication it sells, announced that it has
The company tested 294 batches from 69 companies and found benzene in 27% – many in major national brands like Neutrogena and Banana Boat. Some batches contained as much as three times the emergency FDA limit of 2 parts per million.
Long-term exposure to benzene is known to cause cancer in humans.
“This is especially concerning with sunscreen because multiple FDA studies have shown that sunscreen ingredients absorb through the skin and end up in the blood at high levels,” said David Light, CEO of Valisure.
The FDA is seeking more information about the potential risks from common sunscreen ingredients.
“There is not a safe level of benzene that can exist in sunscreen products,” Christopher Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in Valisure’s FDA petition. “The total mass of sunscreen required to cover and protect the human body, in single daily application or repeated applications daily, means that even benzene at 0.1 ppm in a sunscreen could expose people to excessively high nanogram amounts of benzene.”
Valisure’s testing previously led to FDA recalls of heartburn medications and hand sanitizers.
Examining sunscreen’s environmental impact
Chemicals in sunscreen may be harmful to other forms of life, too. For years, scientists have been examining whether certain chemicals in sunscreen could be causing damage to marine life, in particular the world’s coral reefs. Specific ingredients, including oxybenzone, benzophenone-1, benzophenone-8, OD-PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, nano-titanium dioxide, nano-zinc oxide, octinoxate, and octocrylene, have been identified as potential risks.
Earlier this year, the National Academies of Sciences, Engineering, and Medicine created a committee to review the existing science about the potential environmental hazards. Over the next 2 years, they’ll also consider the public health implications if people stopped using sunscreen.
Valisure’s announcement included this message: “It is important to note that not all sunscreen products contain benzene and that uncontaminated products are available, should continue to be used, and are important for protecting against potentially harmful solar radiation.”
Using sunscreen with SPF 15 every day can lower risk of squamous cell carcinoma by around 40% and melanoma by 50%. The American Academy of Dermatology recommends a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.
A version of this article first appeared on WebMD.com.
Valisure, an online pharmacy known for testing every batch of medication it sells, announced that it has
The company tested 294 batches from 69 companies and found benzene in 27% – many in major national brands like Neutrogena and Banana Boat. Some batches contained as much as three times the emergency FDA limit of 2 parts per million.
Long-term exposure to benzene is known to cause cancer in humans.
“This is especially concerning with sunscreen because multiple FDA studies have shown that sunscreen ingredients absorb through the skin and end up in the blood at high levels,” said David Light, CEO of Valisure.
The FDA is seeking more information about the potential risks from common sunscreen ingredients.
“There is not a safe level of benzene that can exist in sunscreen products,” Christopher Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in Valisure’s FDA petition. “The total mass of sunscreen required to cover and protect the human body, in single daily application or repeated applications daily, means that even benzene at 0.1 ppm in a sunscreen could expose people to excessively high nanogram amounts of benzene.”
Valisure’s testing previously led to FDA recalls of heartburn medications and hand sanitizers.
Examining sunscreen’s environmental impact
Chemicals in sunscreen may be harmful to other forms of life, too. For years, scientists have been examining whether certain chemicals in sunscreen could be causing damage to marine life, in particular the world’s coral reefs. Specific ingredients, including oxybenzone, benzophenone-1, benzophenone-8, OD-PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, nano-titanium dioxide, nano-zinc oxide, octinoxate, and octocrylene, have been identified as potential risks.
Earlier this year, the National Academies of Sciences, Engineering, and Medicine created a committee to review the existing science about the potential environmental hazards. Over the next 2 years, they’ll also consider the public health implications if people stopped using sunscreen.
Valisure’s announcement included this message: “It is important to note that not all sunscreen products contain benzene and that uncontaminated products are available, should continue to be used, and are important for protecting against potentially harmful solar radiation.”
Using sunscreen with SPF 15 every day can lower risk of squamous cell carcinoma by around 40% and melanoma by 50%. The American Academy of Dermatology recommends a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.
A version of this article first appeared on WebMD.com.
Valisure, an online pharmacy known for testing every batch of medication it sells, announced that it has
The company tested 294 batches from 69 companies and found benzene in 27% – many in major national brands like Neutrogena and Banana Boat. Some batches contained as much as three times the emergency FDA limit of 2 parts per million.
Long-term exposure to benzene is known to cause cancer in humans.
“This is especially concerning with sunscreen because multiple FDA studies have shown that sunscreen ingredients absorb through the skin and end up in the blood at high levels,” said David Light, CEO of Valisure.
The FDA is seeking more information about the potential risks from common sunscreen ingredients.
“There is not a safe level of benzene that can exist in sunscreen products,” Christopher Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said in Valisure’s FDA petition. “The total mass of sunscreen required to cover and protect the human body, in single daily application or repeated applications daily, means that even benzene at 0.1 ppm in a sunscreen could expose people to excessively high nanogram amounts of benzene.”
Valisure’s testing previously led to FDA recalls of heartburn medications and hand sanitizers.
Examining sunscreen’s environmental impact
Chemicals in sunscreen may be harmful to other forms of life, too. For years, scientists have been examining whether certain chemicals in sunscreen could be causing damage to marine life, in particular the world’s coral reefs. Specific ingredients, including oxybenzone, benzophenone-1, benzophenone-8, OD-PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, nano-titanium dioxide, nano-zinc oxide, octinoxate, and octocrylene, have been identified as potential risks.
Earlier this year, the National Academies of Sciences, Engineering, and Medicine created a committee to review the existing science about the potential environmental hazards. Over the next 2 years, they’ll also consider the public health implications if people stopped using sunscreen.
Valisure’s announcement included this message: “It is important to note that not all sunscreen products contain benzene and that uncontaminated products are available, should continue to be used, and are important for protecting against potentially harmful solar radiation.”
Using sunscreen with SPF 15 every day can lower risk of squamous cell carcinoma by around 40% and melanoma by 50%. The American Academy of Dermatology recommends a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.
A version of this article first appeared on WebMD.com.
How early can laser treatment for port wine stains in infants be initiated?
without any complications, results from a single-center study showed.
“The current modality of choice for the treatment of port wine birthmarks is pulsed dye laser,” Chelsea Grimes Fidai, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “When performed by a highly trained expert at efficient frequencies, PDL is a safe, effective treatment that is successful in the majority of patients. We know that earlier treatment yields maximal clearance. However, just how early can you initiate treatment?”
To find out, Dr. Fidai, Roy G. Geronemus, MD, and colleagues at the Laser and Skin Surgery Center of New York, conducted a retrospective chart review of 39 infants with port wine birthmarks who were treated with a 595-nm PDL between 2015 and 2020 at the center. Of the 39 infants, the average age at first treatment was 18 days, with a range from 5 to 29 days. The youngest patient was born prematurely at 35 weeks’ gestation and presented for his first treatment even before his expected due date. Most (74%) had facial lesions with the remaining distributed on the trunk or extremities. The average number of treatments was 15 over the course of 15 months.
The initial settings chosen for facial lesions were a 10-mm spot size, a fluence of 8.0 J/cm2, and a 1.5-millisecond pulse duration. For body lesions, the typical initial settings were a 12-mm spot size, a fluence of 6.7 J/cm2, and 1.5-millisecond pulse duration. Corneal eye shields were placed for all cases with port wine birthmarks approaching the eyelid. “We do recommend a treatment interval of every 2-3 weeks, with longer intervals for patients of darker skin type until the child is 2 years old, at which time the interval is increased to every 3-6 months,” said Dr. Fidai.
Patients in the study experienced the expected short-term side effects of erythema, edema, purpura, and mild transient postinflammatory hyperpigmentation, but there were no cases of atrophy, scarring, infection, or permanent pigmentary change.
“Families seeking early treatment of port wine birthmarks can be reassured that it can be safely initiated within the first few days after birth,” Dr. Fidai concluded. “This procedure can be quickly and confidently performed as an in-office procedure without any complications. The early intervention allows for treatment without general anesthesia and it maximizes the chance of significant clearance as early in life as possible.”
During a question-and-answer session, the abstract section chair, Albert Wolkerstorfer, MD, PhD, expressed concern about the effect of PDL on developing infants. “We do repeated treatments at this young age without any type of anesthesia,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam.
“Will that influence the development of the child, especially when I hear there might be 15 or 20 treatments done within the first year of life? I think this is a problem where we need to ask the experts in the field of pain management in children, like pediatric anesthesiologists, to find the right way, because I think that the results that you showed are fantastic. I don’t think we can achieve that at a later age, although there’s no direct comparison at this moment.”
Dr. Fidai said that she understood the concern, but pointed to a 2020 article by Dr. Geronemus and colleagues that assessed treatment tolerance and parental perspective of outpatient PDL treatment for port-wine birthmarks without general anesthesia in infants and toddlers. “The kids recover pretty quickly after the treatment,” she said. “There has never been any longstanding issue from the parents’ perspective.”
Dr. Fidai reported having no financial disclosures. Dr. Geronemus disclosed having financial conflicts with numerous device and pharmaceutical companies. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.
without any complications, results from a single-center study showed.
“The current modality of choice for the treatment of port wine birthmarks is pulsed dye laser,” Chelsea Grimes Fidai, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “When performed by a highly trained expert at efficient frequencies, PDL is a safe, effective treatment that is successful in the majority of patients. We know that earlier treatment yields maximal clearance. However, just how early can you initiate treatment?”
To find out, Dr. Fidai, Roy G. Geronemus, MD, and colleagues at the Laser and Skin Surgery Center of New York, conducted a retrospective chart review of 39 infants with port wine birthmarks who were treated with a 595-nm PDL between 2015 and 2020 at the center. Of the 39 infants, the average age at first treatment was 18 days, with a range from 5 to 29 days. The youngest patient was born prematurely at 35 weeks’ gestation and presented for his first treatment even before his expected due date. Most (74%) had facial lesions with the remaining distributed on the trunk or extremities. The average number of treatments was 15 over the course of 15 months.
The initial settings chosen for facial lesions were a 10-mm spot size, a fluence of 8.0 J/cm2, and a 1.5-millisecond pulse duration. For body lesions, the typical initial settings were a 12-mm spot size, a fluence of 6.7 J/cm2, and 1.5-millisecond pulse duration. Corneal eye shields were placed for all cases with port wine birthmarks approaching the eyelid. “We do recommend a treatment interval of every 2-3 weeks, with longer intervals for patients of darker skin type until the child is 2 years old, at which time the interval is increased to every 3-6 months,” said Dr. Fidai.
Patients in the study experienced the expected short-term side effects of erythema, edema, purpura, and mild transient postinflammatory hyperpigmentation, but there were no cases of atrophy, scarring, infection, or permanent pigmentary change.
“Families seeking early treatment of port wine birthmarks can be reassured that it can be safely initiated within the first few days after birth,” Dr. Fidai concluded. “This procedure can be quickly and confidently performed as an in-office procedure without any complications. The early intervention allows for treatment without general anesthesia and it maximizes the chance of significant clearance as early in life as possible.”
During a question-and-answer session, the abstract section chair, Albert Wolkerstorfer, MD, PhD, expressed concern about the effect of PDL on developing infants. “We do repeated treatments at this young age without any type of anesthesia,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam.
“Will that influence the development of the child, especially when I hear there might be 15 or 20 treatments done within the first year of life? I think this is a problem where we need to ask the experts in the field of pain management in children, like pediatric anesthesiologists, to find the right way, because I think that the results that you showed are fantastic. I don’t think we can achieve that at a later age, although there’s no direct comparison at this moment.”
Dr. Fidai said that she understood the concern, but pointed to a 2020 article by Dr. Geronemus and colleagues that assessed treatment tolerance and parental perspective of outpatient PDL treatment for port-wine birthmarks without general anesthesia in infants and toddlers. “The kids recover pretty quickly after the treatment,” she said. “There has never been any longstanding issue from the parents’ perspective.”
Dr. Fidai reported having no financial disclosures. Dr. Geronemus disclosed having financial conflicts with numerous device and pharmaceutical companies. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.
without any complications, results from a single-center study showed.
“The current modality of choice for the treatment of port wine birthmarks is pulsed dye laser,” Chelsea Grimes Fidai, MD, said during the annual conference of the American Society for Laser Medicine and Surgery. “When performed by a highly trained expert at efficient frequencies, PDL is a safe, effective treatment that is successful in the majority of patients. We know that earlier treatment yields maximal clearance. However, just how early can you initiate treatment?”
To find out, Dr. Fidai, Roy G. Geronemus, MD, and colleagues at the Laser and Skin Surgery Center of New York, conducted a retrospective chart review of 39 infants with port wine birthmarks who were treated with a 595-nm PDL between 2015 and 2020 at the center. Of the 39 infants, the average age at first treatment was 18 days, with a range from 5 to 29 days. The youngest patient was born prematurely at 35 weeks’ gestation and presented for his first treatment even before his expected due date. Most (74%) had facial lesions with the remaining distributed on the trunk or extremities. The average number of treatments was 15 over the course of 15 months.
The initial settings chosen for facial lesions were a 10-mm spot size, a fluence of 8.0 J/cm2, and a 1.5-millisecond pulse duration. For body lesions, the typical initial settings were a 12-mm spot size, a fluence of 6.7 J/cm2, and 1.5-millisecond pulse duration. Corneal eye shields were placed for all cases with port wine birthmarks approaching the eyelid. “We do recommend a treatment interval of every 2-3 weeks, with longer intervals for patients of darker skin type until the child is 2 years old, at which time the interval is increased to every 3-6 months,” said Dr. Fidai.
Patients in the study experienced the expected short-term side effects of erythema, edema, purpura, and mild transient postinflammatory hyperpigmentation, but there were no cases of atrophy, scarring, infection, or permanent pigmentary change.
“Families seeking early treatment of port wine birthmarks can be reassured that it can be safely initiated within the first few days after birth,” Dr. Fidai concluded. “This procedure can be quickly and confidently performed as an in-office procedure without any complications. The early intervention allows for treatment without general anesthesia and it maximizes the chance of significant clearance as early in life as possible.”
During a question-and-answer session, the abstract section chair, Albert Wolkerstorfer, MD, PhD, expressed concern about the effect of PDL on developing infants. “We do repeated treatments at this young age without any type of anesthesia,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam.
“Will that influence the development of the child, especially when I hear there might be 15 or 20 treatments done within the first year of life? I think this is a problem where we need to ask the experts in the field of pain management in children, like pediatric anesthesiologists, to find the right way, because I think that the results that you showed are fantastic. I don’t think we can achieve that at a later age, although there’s no direct comparison at this moment.”
Dr. Fidai said that she understood the concern, but pointed to a 2020 article by Dr. Geronemus and colleagues that assessed treatment tolerance and parental perspective of outpatient PDL treatment for port-wine birthmarks without general anesthesia in infants and toddlers. “The kids recover pretty quickly after the treatment,” she said. “There has never been any longstanding issue from the parents’ perspective.”
Dr. Fidai reported having no financial disclosures. Dr. Geronemus disclosed having financial conflicts with numerous device and pharmaceutical companies. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.
FROM ASLMS 2021