Ob.Gyn. Says Collaboration with Dermatologists Essential for Managing Vulvar Dermatoses

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Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

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Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

Sarah Cigna, MD, sees patients every week with vulvovaginal pain and vulvar dermatoses. She’s an ob.gyn. with a focus on sexual health — often the first physician seen by patients with vulvar pain or itch — and she believes collaboration with dermatologists is essential, especially for complex cases in what she calls a neglected, data-poor area of medicine.

She also recommends that dermatologists have a good understanding of the vestibule, “one of the most important structures in vulvar medicine,” and that they become equipped to recognize generalized and localized causes of vulvar pain and/or itch.

“The problem is, we don’t talk about [vulvovaginal pain and itch] ... it’s taboo and we’re not taught about it in medical school,” Cigna, assistant professor of obstetrics and gynecology at The George Washington University (GWU), Washington, DC, said in a grand rounds lecture held recently at the GWU School of Medicine and Health Sciences Department of Dermatology.

“There are dermatologists who don’t have much training in vulvar dermatology, and a lot of gyns don’t get as much training” as they should, she said in an interview after the lecture. “So who’s looking at people’s vulvar skin and figuring out what’s going on and giving them effective treatments and evidence-based education?”

Cigna and dermatologist Emily Murphy, MD, will be co-directors of a joint ob.gyn-dermatology Vulvar Dermatology Clinic at GWU that will be launched in 2025, with monthly clinics for particularly challenging cases where the etiology is unclear or treatment is ineffective. “We want to collaborate in a more systematic way and put our heads together and think creatively about what will improve patient care,” Cigna said in the interview.

Dermatologists have valuable expertise in the immunology and genetic factors involved in skin disorders, Cigna said. Moreover, Murphy, assistant professor of dermatology and director of the Vulvar Health Program at GWU, said in an interview, dermatologists “are comfortable in going to off-label systemic medications that ob.gyns may not use that often” and bring to the table expertise in various types of procedures.

Murphy recently trained with Melissa Mauskar, MD, associate of dermatology and obstetrics and gynecology at the University of Texas Southwestern, Dallas, and founder and director of the Gynecologic Dermatology Clinic there. “It’s so important for dermatologists to be involved. It just takes some extra training that residents aren’t getting right now,” said Murphy, a member of the newly formed Vulvar Dermatoses Research Consortium.

In her grand rounds lecture, Cigna offered pearls to dermatologists for approaching a history and exam and covered highlights of the diagnosis and treatment of various problems, from vulvar Candida infections and lichen simplex chronicus to vulvar lichen sclerosus (LS), vulvar lichen planus (LP), vulvar Crohn’s disease, pudendal neuralgia, and pelvic floor muscle spasm, as well as the role of mast cell proliferation in vulvar issues.

 

Approaching the History and Exam

A comprehensive history covers the start, duration, and location of pain and/or itching as well as a detailed timeline (such as timing of potential causes, including injuries or births) and symptoms (such as burning, cutting, aching, and stinging). The question of whether pain “is on the outside, at the entrance, or deeper inside” is “crucial, especially for those in dermatology,” Cigna emphasized.

“And if you’re seeing a patient for a vulvar condition, please ask them about sex. Ask, is this affecting your sexual or intimate life with your partner because this can also give you a clue about what’s going on and how you can help them,” she told the audience of dermatologists.

Queries about trauma history (physical and emotional/verbal), competitive sports (such as daily cycling, equestrian, and heavy weight lifting), endometriosis/gynecologic surgery, connective tissue disorders (such as Ehler-Danlos syndrome), and irritable bowel syndrome are all potentially important to consider. It is important to ask about anxiety, depression, and obsessive-compulsive disorder, which do not cause — but are highly associated with — vulvar dermatoses, she said.

A surprisingly large number of people with vulvovaginal issues are being diagnosed with Ehler-Danlos syndrome, so “I’m always asking, are you hypermobile because this might be affecting the musculoskeletal system, which might be affecting the pelvis,” Cigna said. “Anything that affects the pelvis can affect the vulva as well.”

The pelvic examination should be “offered” rather than assumed to be part of the exam, as part of a trauma-informed approach that is crucial for earning trust, she advised. “Just saying, ‘we’re going to talk, and then I can offer you an exam if you like’…patients like it. It helps them feel safer and more open.”

Many diagnoses are differentiated by eliciting pain on the anterior vs the posterior half of the vulvar vestibule — the part of the vulva that lies between the labia minora and is composed of nonkeratinized tissue with embryonic origins in the endoderm. “If you touch on the keratinized skin (of the vulva) and they don’t have pain, but on the vestibule they do have pain, and there is no pain inside the vagina, this suggests there is a vestibular problem,” said Cigna.

Pain/tenderness isolated to the posterior half of the vestibule suggests a muscular cause, and pain in both the posterior and anterior parts of the vestibule suggests a cause that is more systemic or diffuse, which could be a result of a hormonal issue such as one related to oral contraceptives or decreased testosterone, or a nerve-related process.

Cigna uses gentle swipes of a Q-tip moistened with water or gel to examine the vulva rather than a poke or touch, with the exception being the posterior vestibule, which overlies muscle insertion sites. “Make sure to get a baseline in remote areas such as the inner thigh, and always distinguish between ‘scratchy/sensitive’ sensations and pain,” she said, noting the value of having the patient hold a mirror on her inner thigh.

 

Causes of Vulvar Itch: Infectious and Noninfectious

With vulvar candidiasis, a common infectious cause of vulvar itch, “you have to ask if they’re also itching on the inside because if you treat them with a topical and you don’t treat the vaginal yeast infection that may be co-occurring, they’ll keep reseeding their vulvar skin,” Cigna said, “and it will never be fully treated.”

Candida albicans is the most common cause of vulvar or vulvovaginal candidiasis, and resistance to antifungals has been rising. Non-albicans Candida “tends to have even higher resistance rates,” she said. Ordering a sensitivity panel along with the culture is helpful, but “comprehensive vaginal biome” panels are generally not useful. “It’s hard to correlate the information clinically,” she said, “and there’s not always a lot of information about susceptibilities, which is what I really like to know.”

Cigna’s treatments for vaginal infections include miconazole, terconazole, and fluconazole (and occasionally, itraconazole or voriconazole — a “decision we don’t take lightly”). Vulvar treatments include nystatin ointment, clotrimazole cream, and miconazole cream. Often, optimal treatment involves addressing “both inside and out,” she said, noting the importance of also killing yeast in undergarment fabric.

“In my experience, Diflucan [oral fluconazole] doesn’t treat persistent vulvar cutaneous skin yeast well, so while I might try Diflucan, I typically use something topical as well,” she said. “And with vaginal yeast, we do use boric acid from time to time, especially for non-albicans species because it tends to be a little more effective.”

Noninfectious causes of vulvar itch include allergic, neuropathic, and muscular causes, as well as autoimmune dermatoses and mast cell activation syndrome. Well known in dermatology are acute contact dermatitis and lichen simplex chronicus — both characterized by induration, thickening, and a “puffy” erythematous appearance, and worsening of pruritus at night. What may be less appreciated is the long list of implicated allergens , including Always menstrual pads made of a plastic-containing “dry weave” material, Cigna said. There are at least several cotton-only, low-preservative feminine products available on the market, she noted.

 

Common Autoimmune Vulvar Dermatoses: LS and LP

Vulvar LS has traditionally been thought to affect mainly prepubertal and postmenopausal women, but the autoimmune condition is now known to affect more reproductive-age people with vulvas than previously appreciated, Cigna said.

And notably, in an observational web-based study of premenopausal women (aged 18-50 years) with biopsy-confirmed vulvar LS, the leading symptom was not itch but dyspareunia and tearing with intercourse. This means “we’re missing people,” said Cigna, an author of the study. “We think the reason we’re not seeing itch as commonly in this population is that itch is likely mediated by the low estrogen state of pre- and postmenopausal people.”

Vulvar LS also occurs in pregnancy, with symptoms that are either stable or decrease during pregnancy and increase in the postpartum period, as demonstrated in a recently published online survey.

Patients with vulvar LS can present with hypopigmentation, lichenification, and scarring and architectural changes, the latter of which can involve clitoral phimosis, labial resorption, and narrowing of the introitus. (The vaginal mucosa is unaffected.) The presentation can be subtle, especially in premenopausal women, and differentiation between LS, vitiligo, and yeast is sometimes necessary.

A timely biopsy-driven definitive diagnosis is important because vulvar LS increases the risk for cancer if it’s not adequately treated and because long-term steroid use can affect the accuracy of pathology reports. “We really care about keeping this disease in remission as much as possible,” Cigna said. Experts in the field recommend long-term maintenance therapy with a mid-ultra-potent steroid one to three times/week or an alternative. “I’ve just started using ruxolitinib cream, a Janus kinase (JAK) inhibitor, and tacrolimus, a calcineurin inhibitor,” she said.

With vulvar LP, based on current evidence, the risk for malignant transformation is low, but “it crosses into the vagina and can cause vaginal adhesions, so if you’re diagnosing someone with lichen planus, you need to make sure you’re talking with them about dilators, and if you’re not comfortable, send them to [gyn],” she said.

The use of vulvoscopy is important for one’s ability to see the fine Wickham’s striae that often characterize vulvar LP, she noted. Medical treatments for vulvar LP include topical calcineurin inhibitors, high-potency steroids, and JAK inhibitors.

Surgical treatment of vulvar granuloma fissuratum caused by vulvar LS is possible (when the patient is in complete remission, to prevent koebnerization), with daily post-op application of clobetasol and retraction of tissues, noted Cigna, the author of a study on vulvar lysis of adhesions.

With both LS and LP, Cigna said, “don’t forget (consideration of) hormones” as an adjunctive treatment, especially in postmenopausal women. “Patients in a low hormone state will have more flares.”

 

Vulvar Crohn’s

“We all have to know how to look for this,” Cigna said. “Unilateral or asymmetric swelling is classic, but don’t rule out the diagnosis if you see symmetric swelling.” Patients also typically have linear “knife-like” fissures or ulcerations, the vulva “is very indurated,” and “swelling is so intense, the patients are miserable,” she said.

Vulvar Crohn’s disease may precede intestinal disease in 20%-30% of patients, so referral to a gastroenterologist — and ideally subsequent collaboration — is important, as vulvar manifestations are treated with systemic medications typical for Crohn’s.

A biopsy is required for diagnosis, and the pathologist should be advised to look for lichenified squamous mucosa with the Touton giant cell reaction. “Vulvar Crohn’s is a rare enough disorder that if you don’t have an experienced or informed pathologist looking at your specimen, they may miss it because they won’t be looking for it,” Cigna added in the interview. “You should be really clear about what you’re looking for.”

 

Neuropathic Itch, Pelvic Floor Muscle Spasm

Patients with pudendal neuralgia — caused by an injured, entrapped, or irritated pudendal nerve (originating from S2-S4) — typically present with chronic vulvar and pelvic pain that is often unprovoked and worsens with sitting. Itching upon touch is often another symptom, and some patients describe a foreign body sensation. The cause is often trauma (such as an accident or childbirth-related) as opposed to myofascial irritation, Cigna explained in her lecture.

“Your exam will be largely normal, with no skin findings, so patients will get sent away if you don’t know to look for pudendal neuralgia by pressing on the pudendal nerve or doing (or referring for) a diagnostic nerve block,” Cigna added in the interview.

Persistent genital arousal disorder (PGAD) is “more global” in that it can also originate not only from the pudendal nerve but also from nerve roots higher in the spine or even from the brain. “People feel a sense of arousal, but some describe it as an itch,” Cigna said in her lecture, referring to a 2021 consensus document on PGAD/genito-pelvic dysesthesia by the International Society for the Study of Women’s Sexual Health as a valuable resource for understanding and managing the condition.

Diagnosis and treatment usually start with a pudendal nerve block with a combination of steroid and anesthetic. If this does not relieve arousal/itching, the next step may be an MRI to look higher in the spine.

 

Pelvic Floor Muscle Spasm

Vulvar pain, skin itching, and irritation can be symptoms of pelvic floor muscle spasm. “Oftentimes people come to me and say, ‘I have a dermatologic problem,’” Cigna said. “The skin may look red and erythematous, but it’s probably more likely a muscle problem when you’re not finding anything, and no amount of steroid will help the itch go away when the problem lies underneath.”

Co-occurring symptoms can include vaginal dryness, clitoral pain, urethral discomfort, bladder pain/irritation, increased urgency, constipation, and anal fissures. The first-line treatment approach is pelvic floor therapy.

“Pelvic floor therapy is not just for incontinence. It’s also for pain and discomfort from muscles,” she said, noting that most patients with vulvar disorders are referred for pelvic floor therapy. “Almost all of them end up having pelvic floor dysfunction because the pelvic floor muscles spasm whenever there’s pain or inflammation.”

 

A Cautionary Word on Vulvodynia, and a Mast Cell Paradigm to Explore

Vulvodynia is defined as persistent pain of at least 3 months’ duration with no clear cause. “These are the patients with no skin findings,” Cigna said. But in most cases, she said, careful investigation identifies causes that are musculoskeletal, hormonal, or nerve-related.

“It’s a term that’s thrown around a lot — it’s kind of a catchall. Yet it should be a small minority of patients who truly have a diagnosis of vulvodynia,” she said.

In the early stages of investigation is the idea that mast cell proliferation and mast cell activation may play a role in some cases of vulvar and vestibular pain and itching. “We see that some patients with vulvodynia and vestibulodynia have mast cells that are increased in number in the epithelium and beneath the epithelium, and nerve staining shows an increased number of nerve endings traveling into the epithelium,” Cigna said.

“We do diagnose some people clinically” based on urticaria and other symptoms suggestive of mast cell proliferation/activation (such as flushing, abdominal cramping, diarrhea, hypotensive syncope or near syncope, and tachycardia), and “then we send them to the allergist for testing,” Cigna said.

Cigna and Murphy have no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

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Tips on Handling a Negative Patient Review

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Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

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Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Early in his career as a physician associate in dermatology, Joe Cari, MPAS, PA-C, received a negative online review from a patient that really got under his skin.

“It said something like, ‘Do not see Joe the fake doctor. Joe should have his medical license pulled. He didn’t listen to me. He threw drugs at me and he only talked to me for 5 minutes,’ ” Cari, who practices at the University of Colorado Anschutz Medical Campus, Aurora, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Being early in my practice, that hurt; it was a jab to the heart. I had about 20-30 five-star reviews, but I laser-focused on the bad one.”

When a review questions competence, it can feel personal, he continued, even though it often reflects the reviewer’s emotions or experience. Cari, a former Marine, said that clinicians can mitigate emotional responses to negative reviews by building emotional resilience. He draws inspiration from Stoicism (the school of philosophy that originated during the Hellenistic period), which emphasizes developing inner resilience, managing emotions, “and cultivating virtues such as wisdom, courage, and self-discipline,” he said. 

Cari often cites a quote from Marcus Aurelius, the former Roman Emperor and Stoic philosopher: “You have power over your mind — not outside events. Realize this, and you will find strength.” Another quote that changed his perspective comes from the Stoic Epictetus: “We cannot control the external events around us, but we can control our reactions to them.”

On a practical level, Cari shared several ways that clinicians can cultivate emotional resilience when faced with a negative review.

Practice mindfulness. Reading reviews in a nonjudgmental way “allows us to pause, reflect, and respond thoughtfully rather than react emotionally,” he explained. He also recommended setting clear boundaries between work and personal life to prevent burnout and maintain a healthy work–life balance. Realizing he needed time to decompress after a previous job that involved a 1-hour drive, he began listening to audiobooks on his way home. “I set that time aside for myself to listen, relax, and let all my troubles from work melt away,” Cari said. 

Develop a support network. This includes both professionals, such as therapists, and personal connections, such as colleagues, mentors, and friends.

Practice self-care. Whether it’s yoga, running, jogging, spending time with loved ones, or playing with your dog, find activities that help you recharge. “Most importantly, get some rest and take a vacation,” Cari advised. “Your body is like a machine. If you do not rest it and take care of it, it will slowly breakdown and burnout.”

Practice equanimity. Cari defined this as mental calmness, composure, and evenness of temper, especially in a difficult situation. “Maintaining a calm and balanced state of mind, regardless of external circumstances, is a core Stoic and military practice,” he said.

According to data he attributed to reviewtrackers, an estimated 60% of reviews are influenced by the reviewer’s personal stress or mood, “so don’t take [bad reviews] personally,” he said. Instead, view criticism as an opportunity for self-improvement and to gain insight into others’ perspectives. Cari recommended practicing indifference to both praise and blame. “Do not seek validation or be disheartened by negative reviews,” he said. “Remain focused on your own standards of excellence.”

Cari has reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

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Expert Reviews Options for Revitalizing Dystrophic Nails

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After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

Dr. Tracey C. Vlahovic

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, ureaglycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

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After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

Dr. Tracey C. Vlahovic

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, ureaglycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

After antifungal therapy for fungal nail disease, some dystrophy may persist, which can be addressed by several available treatments. 

“With the fingernails, we don’t often see onychomycosis, but with toenails, we certainly do,” Tracey C. Vlahovic, DPM, a professor at the Samuel Merritt University College of Podiatric Medicine, Oakland, California, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “But toenails are subject to a lot of forces beyond just fungal [infections]. We have the wear and tear of wearing shoes, gait, and other physical activity.”

 

Dr. Tracey C. Vlahovic

For example, she continued, some runners develop second-toenail dystrophy “because there’s constant repetitive trauma to the toenail, and [poorly fitting] shoes can contribute to that. Biomechanical issues are a unique consideration when you’re dealing with toenail issues.”

Vlahovic highlighted several options that can help improve the appearance of dystrophic nails as they recover or grow back:

Urea nail preparations: To temporarily soften the nail.

Genadur (hydroxypropyl chitosan): This product “is used mainly for psoriatic nails, but I use it for all different kinds of nail dystrophy,” she said.

DermaNail (acetyl mandelic acid solution): This can be used for brittle nails and fingernails. Vlahovic said she recommends it be used on toenails “in addition to the onychomycosis and other nail dystrophy treatments that I’m doing because it really helps to hydrate the nail unit.”

Kerasal Fungal Nail Renewal (ingredients include propylene glycol, ureaglycerin, and lactic acid): This product is used “for smoothing out the appearance of the nail,” she said.

KeryFlex: Applied in an office setting, this resin-based product restores the appearance of an individual’s natural nails. “It comes in two colors [and] absorbs the shock of what is going on mechanically with the feet,” Vlahovic said. “So, if I’m treating a ballet dancer performing en pointe, or a soccer player, it’s something I can use to protect the nail, but also to make it cosmetically more acceptable.”

NECPro: A nail reconstruction method that involves the use of a composite used mainly by podiatrists, it “helps you not only create a barrier, but to create a natural-looking color that matches your own nail color,” she said.

In Vlahovic’s experience, KeryFlex and NECPro last 6-8 weeks. “You can use nail polish on top of them if you’d like, but they’re basically cosmetic barriers to protect the nail unit,” she said.

Vlahovic has disclosed being a consultant and investigator for Ortho Dermatologics and Sagis Diagnostics.

 

A version of this article appeared on Medscape.com.

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Topical Retinoids a Key Component of Acne Treatment Regimens

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No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

Dr. Hilary E. Baldwin

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

  • Use a pea-sized amount for the entire affected area and avoid spot treatments.
  • Start with every other day application.
  • Moisturize regularly, possibly applying moisturizer before the retinoid.
  • Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
  • Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

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No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

Dr. Hilary E. Baldwin

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

  • Use a pea-sized amount for the entire affected area and avoid spot treatments.
  • Start with every other day application.
  • Moisturize regularly, possibly applying moisturizer before the retinoid.
  • Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
  • Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

No matter which treatment regimen is recommended for patients with acne, it should always include a topical retinoid, according to dermatologist Hilary Baldwin, MD.

Patients with successfully treated acne typically use an average of 2.53 different medications, Baldwin, director of the Acne Treatment & Research Center, Brooklyn, New York, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference.

 

Dr. Hilary E. Baldwin

“Combination treatment is the name of the game, but how do we convince our patients that what we chose is carefully orchestrated?” she said. “Combination therapy is much more effective, yet we’re always told, ‘keep it simple.’ The trick is to use combination products that have two or three medications in them — fixed combinations and products with excellent vehicles.”

No matter what treatment regimen is recommended for patients with acne, she continued, it should always include a topical retinoid. Tretinoin was the first topical retinoid approved for acne treatment in 1971, followed by adapalene in 1996, tazarotene in 1997, and trifarotene in 2019. According to a review article , topical retinoids inhibit the formation of microcomedones, reduce mature comedones and inflammatory lesions, enhance penetration of other drugs, reduce and prevent scarring, reduce hyperpigmentation, and maintain remission of acne.

More recently, authors of the 2024 American Academy of Dermatology guidelines of care for the management of acne vulgaris strongly recommended the use of topical retinoids based on moderate certainty evidence in the medial literature. Strong recommendations are also made for benzoyl peroxide, topical antibiotics, and oral doxycycline.

Baldwin noted that the benefits of retinoids include their comedolytic and anti-comedogenic properties, their effectiveness in treating inflammatory lesions, and their suitability for long-term maintenance. However, their drawbacks involve the potential for irritancy, which can be concentration- and vehicle-dependent.

Irritancy “maxes out at 1-2 weeks, but the problem is you lose the patient at 2 weeks unless they know it’s coming,” she said, noting that she once heard the 2-week mark characterized as a “crisis of confidence.” Patients “came in with a bunch of pimples, and now they’re red and flaky and burning and stinging [from the retinoid], yet they still have pimples,” Baldwin said. “You really need to talk them through that 2-week mark [or] they’re going to stop the medication.”

To improve retinoid tolerability, Baldwin offered the following tips:

  • Use a pea-sized amount for the entire affected area and avoid spot treatments.
  • Start with every other day application.
  • Moisturize regularly, possibly applying moisturizer before the retinoid.
  • Consider switching to a different formulation with an alternative vehicle or retinoid delivery system. Adapalene and tazarotene are the only retinoids that have proven to be stable in the presence of benzoyl peroxide, she said.
  • Be persistent. “There is no such thing as a patient who cannot tolerate a retinoid,” said Baldwin, the lead author of a review on the evolution of topical retinoids for acne. “It’s because of a provider who failed to provide a sufficient amount of information to allow the patient to eventually be able to tolerate a retinoid.”

Baldwin also referred to an independent meta-analysis of 221 trials comparing the efficacy of pharmacological therapies for acne in patients of any age, which found that the percentage reduction in total lesion count, compared with placebo, was the highest with oral isotretinoin (mean difference [MD], 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (MD, 38.15; P = .95), and by triple therapy containing an oral antibiotic, a topical retinoid, and benzoyl peroxide (MD, 34.83; P = .90).

Baldwin is a former president of the American Acne & Rosacea Society and is the SDPA conference medical director. She disclosed being a speaker, consultant, and/or an advisory board member for Almirall, Arcutis, Bausch, Beiersdorf, Cutera, Galderma, Journey, Kenvue, La Roche-Posay, L’Oreal, Sanofi, Sun Pharma, and Tarsus Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

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New Cause of Sexually Transmitted Fungal Infection Reported in MSM

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A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.

 

Dr. Avrom S. Caplan

“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.

“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.

The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.

All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.

Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.

Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.” 

Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.

“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.” 

 

Encourage Reporting and Identify New Infections

“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.

“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.

In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.” 

Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.

The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”

“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.

Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.” 

Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.

The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

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A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.

 

Dr. Avrom S. Caplan

“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.

“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.

The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.

All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.

Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.

Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.” 

Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.

“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.” 

 

Encourage Reporting and Identify New Infections

“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.

“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.

In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.” 

Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.

The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”

“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.

Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.” 

Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.

The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

A dermatophyte known as Trichophyton mentagrophytes genotype VII (TMVII) has been identified as the cause of an emerging sexually transmitted fungal infection in four adults in the United States, according to a paper published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

TMVII is a sexually transmitted fungus that causes genital tinea; the fungus might be misidentified as eczema, psoriasis, or other dermatologic conditions, Jason E. Zucker, MD, an infectious disease specialist at Columbia University Irving Medical Center, New York City, and colleagues wrote.

 

Dr. Avrom S. Caplan

“Dermatophyte infections, including TMVII, are spread through direct skin-to-skin contact,” corresponding author Avrom S. Caplan, MD, a dermatologist at New York University Grossman School of Medicine, New York City, said in an interview.

“In the United States, to our knowledge, the infection has only been in MSM [men who have sex with men], but there have been reports of TMVII in Europe in non-MSM patients, including among patients who traveled to Southeast Asia for sex tourism or partners of people who have been infected with TMVII,” he said.

The four patients were diagnosed with tinea between April 2024 and July 2024, and fungal cultures and DNA sequencing identified TMVII as the cause of the infection. All four patients were cisgender men aged 30-39 years from New York City who reported recent sexual contact with other men; one was a sex worker, two had sex with each other, and one reported recent travel to Europe.

All four patients presented with rashes on the face, buttocks, or genitals; all were successfully treated with antifungals, the authors wrote.

Individuals with genital lesions who are sexually active should be seen by a healthcare provider, and TMVII should be considered, especially in the event of scaly, itchy, or inflamed rashes elsewhere on the body, Caplan told this news organization.

Additionally, “If someone presents for a medical evaluation and has ringworm on the buttocks, face, or elsewhere, especially if they are sexually active, the question of TMVII should arise, and the patient should be asked about possible genital lesions as well,” he said. “Any patient diagnosed with an STI [sexually transmitted infection], including MSM patients, should be evaluated appropriately for other STIs including TMVII.” 

Continued surveillance and monitoring are needed to track TMVII and to better understand emerging infections, Caplan told this news organization. Clinicians can find more information and a dermatophyte registry via the American Academy of Dermatology websites on emerging diseases in general and dermatophytes in particular.

“We also need better access to testing and more rapid confirmatory testing to detect emerging dermatophyte strains and monitor antifungal resistance patterns,” Caplan added. “At this time, we do not have evidence to suggest there is antifungal resistance in TMVII, which also distinguishes it from T indotineae.” 

 

Encourage Reporting and Identify New Infections

“Emerging infections can mimic noninfectious disease processes, which can make the diagnosis challenging,” Shirin A. Mazumder, MD, associate professor and infectious disease specialist at the University of Tennessee Health Science Center, Memphis, said in an interview.

“Monitoring emerging infections can be difficult if the cases are not reported and if the disease is not widespread,” Mazumder noted. Educating clinicians with case reports and encouraging them to report unusual cases to public health helps to overcome this challenge.

In the clinical setting, skin lesions that fail to respond or worsen with the application of topical steroids could be a red flag for TMVII, Mazumder told this news organization. “Since the skin findings of TMVII can closely resemble noninfectious processes such as eczema or psoriasis, the use of topical corticosteroids may have already been tried before the diagnosis of TMVII is considered.” 

Also, location matters in making the diagnosis. TMVII lesions occur on the face, genitals, extremities, trunk, and buttocks. Obtaining a thorough sexual history is important because the fungus spreads from close contact through sexual exposure, Mazumder added.

The most effective treatment for TMVII infections remains to be determined, Mazumder said. “Treatment considerations such as combination treatment with oral and topical antifungal medications vs oral antifungal medication alone is something that needs further research along with the best treatment duration.”

“Determining the rate of transmissibility between contacts, when someone is considered to be the most infectious, how long someone is considered infectious once infected, and rates of reinfection are questions that may benefit from further study,” she added.

Although the current cases are reported in MSM, determining how TMVII affects other patient populations will be interesting as more cases are reported, said Mazumder. “Further understanding of how different degrees of immunosuppression affect TMVII disease course is another important consideration.” 

Finally, determining the rate of long-term sequelae from TMVII infection and the rate of bacterial co-infection will help better understand TMVII, she said.

The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

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Study Finds No Significant Effect of Low-Dose Oral Minoxidil on BP

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TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

  • Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
  • Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
  • Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

  • Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
  • LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
  • LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
  • Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

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

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TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

  • Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
  • Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
  • Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

  • Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
  • LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
  • LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
  • Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

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

 

TOPLINE:

Low-dose oral minoxidil (LDOM), used off-label to treat alopecia, does not significantly affect blood pressure (BP) in patients with alopecia, but is associated with a slight increase in heart rate and a 5% incidence of hypotensive symptoms.

METHODOLOGY:

  • Researchers conducted a systematic review and meta-analysis of 16 studies, which involved 2387 patients with alopecia (60.7% women) who received minoxidil, a vasodilator originally developed as an antihypertensive, at doses of 5 mg or less per day.
  • Outcomes included changes in mean arterial pressure, systolic BP, diastolic BP, and heart rate.
  • Mean differences were calculated between pretreatment and posttreatment values.

TAKEAWAY:

  • Hypotensive symptoms were reported in 5% patients, with no significant hypotensive episodes. About 1.8% patients experienced lightheadedness or syncope, 1.2% experienced dizziness, 0.9% had tachycardia, and 0.8% had palpitations.
  • LDOM did not significantly alter systolic BP (mean difference, –0.13; 95% CI, –2.67 to 2.41), diastolic BP (mean difference, –1.25; 95% CI, –3.21 to 0.71), and mean arterial pressure (mean difference, –1.92; 95% CI, –4.00 to 0.17).
  • LDOM led to a significant increase in heart rate (mean difference, 2.67 beats/min; 95% CI, 0.34-5.01), a difference the authors wrote would “likely not be clinically significant for most patients.”
  • Hypertrichosis was the most common side effect (59.6%) and reason for stopping treatment (accounting for nearly 35% of discontinuations).

IN PRACTICE:

“LDOM appears to be a safe treatment for alopecia with no significant impact on blood pressure,” the authors wrote, noting that the study “addresses gaps in clinical knowledge involving LDOM.” Based on their results, they recommended that BP and heart rate “do not need to be closely monitored in patients without prior cardiovascular risk history.”

SOURCE:

The study was led by Matthew Chen, BS, Stony Brook Dermatology in New York. It was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The studies included had small sample sizes and retrospective designs, which may limit the reliability of the findings. Additional limitations include the absence of control groups, a potential recall bias in adverse effect reporting, and variability in dosing regimens and BP monitoring. 

DISCLOSURES:

The authors reported no external funding or conflicts of interest.

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

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Barzolvolimab Effective for CSU in Phase 2 Study

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Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

 

 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

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Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

 

 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

 

 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

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Children With Severe Atopic Dermatitis Catch Up on Growth With Dupilumab

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Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

 

 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

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Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

 

 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

 

 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

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Nemolizumab Benefits for Atopic Dermatitis Maintained in Long-Term Follow-Up Study

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The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

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The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

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Lichen Planus Responds to Treatment with Topical Ruxolitinib in Phase 2 Study

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Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold
Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

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Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold
Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold
Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

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