Internal Medicine News

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.

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.

You’re invited to a dinner party but you struggle to make small talk. Do not worry; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.

1. The Predinner Cocktails: A Lesson in Reverse Causation

Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.

Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more. 

But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.

But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.

You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.

Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.

 

2. The Hors D’oeuvres — The Importance of RCTs

Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.

Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.

This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.

Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall. 

A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.

The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.

 

3. The Main Course — Absolute vs Relative Risk

When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.

Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)

This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.

Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.

 

4. Dessert — Funding

By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence. 

Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.

The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.

But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.

COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers. 

We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.

 

The Final Goodbyes — Summarizing Your Case

As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food. 

And they will no doubt thank you for it by never inviting you to another dinner party!

Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.

A version of this article appeared on Medscape.com.

You’re invited to a dinner party but you struggle to make small talk. Do not worry; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.

1. The Predinner Cocktails: A Lesson in Reverse Causation

Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.

Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more. 

But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.

But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.

You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.

Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.

 

2. The Hors D’oeuvres — The Importance of RCTs

Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.

Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.

This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.

Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall. 

A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.

The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.

 

3. The Main Course — Absolute vs Relative Risk

When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.

Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)

This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.

Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.

 

4. Dessert — Funding

By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence. 

Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.

The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.

But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.

COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers. 

We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.

 

The Final Goodbyes — Summarizing Your Case

As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food. 

And they will no doubt thank you for it by never inviting you to another dinner party!

Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.

A version of this article appeared on Medscape.com.

You’re invited to a dinner party but you struggle to make small talk. Do not worry; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.

1. The Predinner Cocktails: A Lesson in Reverse Causation

Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.

Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more. 

But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.

But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.

You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.

Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.

 

2. The Hors D’oeuvres — The Importance of RCTs

Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.

Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.

This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.

Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall. 

A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.

The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.

 

3. The Main Course — Absolute vs Relative Risk

When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.

Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)

This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.

Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.

 

4. Dessert — Funding

By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence. 

Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.

The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.

But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.

COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers. 

We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.

 

The Final Goodbyes — Summarizing Your Case

As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food. 

And they will no doubt thank you for it by never inviting you to another dinner party!

Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.

A version of this article appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

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

VANCOUVER, BRITISH COLUMBIA — Conditions like diabetes and dementia are common in patients who are admitted to long-term care facilities, but aggressive management of these conditions in long-term care residents is not recommended, according to a presentation given at the Family Medicine Forum (FMF) 2024.

Hospitalizations for hypoglycemia are risky for patients with diabetes who are residents of long-term care facilities, particularly those aged 75 years or older, said Adam Gurau, MD, a family physician in Toronto. Gurau completed a fellowship in care of the elderly at the University of Toronto, in Ontario, Canada.

“A lot of studies have shown diabetes-related hospitalizations,” said Gurau. He cited a 2014 study that found that hypoglycemia hospitalization rates were twice as high in older patients (age, 75 years or older) as in younger patients (age, 65-74 years).

“It is important to keep in mind that our residents in long-term care are at increasing risk for hypoglycemia, and we really should try to reduce [this risk] and not use dangerous medications or potentially dangerous [means of] diabetes management,” said Gurau.

A Canadian study that examined the composite risk for emergency department visits, hospitalizations, or death within 30 days of reaching intensive glycemic control with high-risk agents (such as insulin or sulfonylureas) suggested little benefit and possible harm in using these agents in adults aged 75 years or older.

In addition, current guidelines on diabetes management encourage a different approach. “Looking at some of the more recent North American guidelines, many of them actually now recommend relaxing glycemic targets to reduce overtreatment and prevent hypoglycemia,” said Gurau.

 

Deprescribing Medications

Medication reviews present opportunities for taking a global view of a patient’s treatments and determining whether any drug can be removed from the list. “What we want to do is optimize medications,” said Gurau. “We’re not talking about adding medications. We’re talking about removing medications, which is, I think, what we should be doing.”

Some research suggests that patients are open to deprescribing. One survey examined older adults (mean age, 79.1 years) with three or more chronic conditions who had been prescribed at least five medications. The researchers found that most participants (77%) were willing to deprescribe one or more medicines if a doctor advised that it was possible. “General practitioners may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use,” the researchers wrote.

About 62% of seniors living in a residential care home have a diagnosis of Alzheimer’s disease or another dementia, according to the Alzheimer Society of Canada. Evidence suggests that nonpharmacologic approaches, such as massage and touch therapy and music, can manage neuropsychiatric symptoms, such as aggression and agitation, that are associated with dementia in older adults, noted Gurau.

“We want to focus on nonpharmacologic approaches for many of these [long-term care] residents,” said Gurau. “We have to do as much as we can to exhaust all the nonpharmacologic approaches.”

 

Preventing Hospitalizations

Another challenge to tackle in long-term care is the unnecessary transfer of residents to hospital emergency departments, according to Gurau. “In many situations, it’s worth trying as hard as we can to treat them in the nursing home, as opposed to having them go to hospital.”

Researchers estimated that 25% of the transfers from long-term care facilities in Canada to hospital emergency departments in 2014 were potentially preventable.

Urinary tract infections accounted for 30% of hospital emergency department visits for potentially preventable conditions by older patients who are residents in long-term care, according to 2013-2014 data from the Canadian Institute for Health Information.

“There are lots of downsides to going to the hospital [from long-term care],” Gurau told this news organization. “There are risks for infections, risks for increasing delirium and agitation [in patients with dementia], and risks for other behavior that can really impact somebody’s life.”

Gurau reported having no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — Conditions like diabetes and dementia are common in patients who are admitted to long-term care facilities, but aggressive management of these conditions in long-term care residents is not recommended, according to a presentation given at the Family Medicine Forum (FMF) 2024.

Hospitalizations for hypoglycemia are risky for patients with diabetes who are residents of long-term care facilities, particularly those aged 75 years or older, said Adam Gurau, MD, a family physician in Toronto. Gurau completed a fellowship in care of the elderly at the University of Toronto, in Ontario, Canada.

“A lot of studies have shown diabetes-related hospitalizations,” said Gurau. He cited a 2014 study that found that hypoglycemia hospitalization rates were twice as high in older patients (age, 75 years or older) as in younger patients (age, 65-74 years).

“It is important to keep in mind that our residents in long-term care are at increasing risk for hypoglycemia, and we really should try to reduce [this risk] and not use dangerous medications or potentially dangerous [means of] diabetes management,” said Gurau.

A Canadian study that examined the composite risk for emergency department visits, hospitalizations, or death within 30 days of reaching intensive glycemic control with high-risk agents (such as insulin or sulfonylureas) suggested little benefit and possible harm in using these agents in adults aged 75 years or older.

In addition, current guidelines on diabetes management encourage a different approach. “Looking at some of the more recent North American guidelines, many of them actually now recommend relaxing glycemic targets to reduce overtreatment and prevent hypoglycemia,” said Gurau.

 

Deprescribing Medications

Medication reviews present opportunities for taking a global view of a patient’s treatments and determining whether any drug can be removed from the list. “What we want to do is optimize medications,” said Gurau. “We’re not talking about adding medications. We’re talking about removing medications, which is, I think, what we should be doing.”

Some research suggests that patients are open to deprescribing. One survey examined older adults (mean age, 79.1 years) with three or more chronic conditions who had been prescribed at least five medications. The researchers found that most participants (77%) were willing to deprescribe one or more medicines if a doctor advised that it was possible. “General practitioners may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use,” the researchers wrote.

About 62% of seniors living in a residential care home have a diagnosis of Alzheimer’s disease or another dementia, according to the Alzheimer Society of Canada. Evidence suggests that nonpharmacologic approaches, such as massage and touch therapy and music, can manage neuropsychiatric symptoms, such as aggression and agitation, that are associated with dementia in older adults, noted Gurau.

“We want to focus on nonpharmacologic approaches for many of these [long-term care] residents,” said Gurau. “We have to do as much as we can to exhaust all the nonpharmacologic approaches.”

 

Preventing Hospitalizations

Another challenge to tackle in long-term care is the unnecessary transfer of residents to hospital emergency departments, according to Gurau. “In many situations, it’s worth trying as hard as we can to treat them in the nursing home, as opposed to having them go to hospital.”

Researchers estimated that 25% of the transfers from long-term care facilities in Canada to hospital emergency departments in 2014 were potentially preventable.

Urinary tract infections accounted for 30% of hospital emergency department visits for potentially preventable conditions by older patients who are residents in long-term care, according to 2013-2014 data from the Canadian Institute for Health Information.

“There are lots of downsides to going to the hospital [from long-term care],” Gurau told this news organization. “There are risks for infections, risks for increasing delirium and agitation [in patients with dementia], and risks for other behavior that can really impact somebody’s life.”

Gurau reported having no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — Conditions like diabetes and dementia are common in patients who are admitted to long-term care facilities, but aggressive management of these conditions in long-term care residents is not recommended, according to a presentation given at the Family Medicine Forum (FMF) 2024.

Hospitalizations for hypoglycemia are risky for patients with diabetes who are residents of long-term care facilities, particularly those aged 75 years or older, said Adam Gurau, MD, a family physician in Toronto. Gurau completed a fellowship in care of the elderly at the University of Toronto, in Ontario, Canada.

“A lot of studies have shown diabetes-related hospitalizations,” said Gurau. He cited a 2014 study that found that hypoglycemia hospitalization rates were twice as high in older patients (age, 75 years or older) as in younger patients (age, 65-74 years).

“It is important to keep in mind that our residents in long-term care are at increasing risk for hypoglycemia, and we really should try to reduce [this risk] and not use dangerous medications or potentially dangerous [means of] diabetes management,” said Gurau.

A Canadian study that examined the composite risk for emergency department visits, hospitalizations, or death within 30 days of reaching intensive glycemic control with high-risk agents (such as insulin or sulfonylureas) suggested little benefit and possible harm in using these agents in adults aged 75 years or older.

In addition, current guidelines on diabetes management encourage a different approach. “Looking at some of the more recent North American guidelines, many of them actually now recommend relaxing glycemic targets to reduce overtreatment and prevent hypoglycemia,” said Gurau.

 

Deprescribing Medications

Medication reviews present opportunities for taking a global view of a patient’s treatments and determining whether any drug can be removed from the list. “What we want to do is optimize medications,” said Gurau. “We’re not talking about adding medications. We’re talking about removing medications, which is, I think, what we should be doing.”

Some research suggests that patients are open to deprescribing. One survey examined older adults (mean age, 79.1 years) with three or more chronic conditions who had been prescribed at least five medications. The researchers found that most participants (77%) were willing to deprescribe one or more medicines if a doctor advised that it was possible. “General practitioners may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use,” the researchers wrote.

About 62% of seniors living in a residential care home have a diagnosis of Alzheimer’s disease or another dementia, according to the Alzheimer Society of Canada. Evidence suggests that nonpharmacologic approaches, such as massage and touch therapy and music, can manage neuropsychiatric symptoms, such as aggression and agitation, that are associated with dementia in older adults, noted Gurau.

“We want to focus on nonpharmacologic approaches for many of these [long-term care] residents,” said Gurau. “We have to do as much as we can to exhaust all the nonpharmacologic approaches.”

 

Preventing Hospitalizations

Another challenge to tackle in long-term care is the unnecessary transfer of residents to hospital emergency departments, according to Gurau. “In many situations, it’s worth trying as hard as we can to treat them in the nursing home, as opposed to having them go to hospital.”

Researchers estimated that 25% of the transfers from long-term care facilities in Canada to hospital emergency departments in 2014 were potentially preventable.

Urinary tract infections accounted for 30% of hospital emergency department visits for potentially preventable conditions by older patients who are residents in long-term care, according to 2013-2014 data from the Canadian Institute for Health Information.

“There are lots of downsides to going to the hospital [from long-term care],” Gurau told this news organization. “There are risks for infections, risks for increasing delirium and agitation [in patients with dementia], and risks for other behavior that can really impact somebody’s life.”

Gurau reported having no relevant financial relationships.

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