David Levinthal, MD, PhD: Cyclic Vomiting Syndrome Diagnosis, Management

A new clinical practice update from the American Gastroenterological Association (AGA) is providing clinicians and patients with guidance for recognizing the signs and symptoms of cyclic vomiting syndrome (CVS).

Published on July 16, 2024, in Gastroenterology, the guidelines review the available evidence and provide expert advice regarding the diagnosis and management of CVS, a highly prevalent yet poorly recognized condition that is often underdiagnosed and undertreated.

The clinical practice update emphasizes the importance of considering a CVS diagnosis in any adult patient presenting with episodic bouts of repetitive vomiting, also highlighting signs and symptoms informing a potential CVS diagnosis and the different phases of CVS. The second half of the guidance focuses on how to manage CVS once it is diagnosed, shining light on the importance of recognizing and addressing comorbid conditions, avoiding triggers during the inter-episodic phase, and when to consider prophylactic and abortive therapy.

For further insight into what CVS is, the importance of providing patients with a diagnosis, and key takeaways from the AGA clinical practice update, the editorial team of HCPLive Gastroenterology spoke with David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center.

HCPLive Gastroenterology: What is cyclic vomiting syndrome? What are some of the key signs and symptoms, and how do they impact patients?

Levinthal: We still don't fully understand cyclic vomiting syndrome and the pathophysiologic basis of that illness. It's diagnosed as a syndrome because it’s truly a collection of symptoms. Cyclic vomiting syndrome is regarded as a disorder of gut-brain interaction, or DGBI, and is defined by the Rome IV criteria of functional illnesses.

In essence, we don't know what causes cyclic vomiting syndrome. This is a disorder that affects both children and adults, and it's probably much more prevalent in adults than was once thought. This was originally believed to be primarily a pediatric illness. Only in the last 10 to 15 years or so has there really been an increased recognition that it's present in adults.

The defining feature of cyclic vomiting syndrome is episodic bouts of uncontrollable, intense nausea and repeated vomiting and retching. It's horrible for patients to experience. One can imagine feeling normal most of the time and then having some symptoms heralding an attack come on within minutes to an hour before the transition to uncontrollable stretching and vomiting that can last for hours to days. Patients recover from this acute illness and then they go about their normal lives in between attacks, so it's truly an episodic illness in which most of the time someone is classically asymptomatic and then transitions into this horrible bout of nausea and vomiting.

In a way, it's very similar to migraine, another episodic disorder. Indeed, there's a clinical overlap of people who have cyclic vomiting syndrome and an increased rate of migraine as well. There's some thought that there may be a neurologic basis to the illness, but we don't know enough about it.

HCPLive Gastroenterology: Why is a diagnosis such a powerful tool in CVS? As important as it is, why do patients frequently experience delays in receiving a diagnosis?

Levinthal: The diagnosis of cyclic vomiting syndrome is a powerful tool because having that diagnosis informs treatment and management. If we can improve the detection and recognition of cyclic vomiting syndrome by the medical community, patients are going to be helped much faster. There is a well-known diagnostic delay for most adult patients with cyclic vomit syndrome that can last several years without receiving any clarity on what's happening.

Perhaps due to the fragmented nature of the healthcare system, patients go into an emergency room seeing different providers, and there's no one person seeing the entire pattern. That may account for some of the delay, but a lot of it is actually the lack of recognition that CVS is a legitimate, known disorder. That kind of plays into the idea that CVS may be rare in adults, and that simply is not true. Some large epidemiologic studies have suggested the prevalence of CVS in the adult population as high as 2%, so that would not be rare.

It really should be on the radar of almost every clinician who sees any patient: primary care doctors, practitioners, emergency room physicians, and obviously gastroenterologists. We likely see CVS patients more than we recognize, so I think improving the recognition is the key to getting patients the help they need. The recognition of that episodic pattern is really the critical leap to diagnosis.

HCPLive Gastroenterology: How has our understanding of CVS evolved over time? How is this reflected in the clinical practice update, and what are some of the key takeaways from this update?

Levinthal: Cyclic vomiting syndrome has been around for a long time, but it took the advocacy of a few clinicians to promote the illness and start to define it. It is somewhat surprising that it was poorly recognized for so long. Every survey that has gone out to identify patients that meet the Rome IV criteria gets at least a 1% prevalence, so this is certainly not a rare illness.

I think simply recognizing cyclic vomiting syndrome, which came into existence as a diagnosis in the Rome III criteria, really accelerated the legitimacy of the illness and put it on the radar. I think there is an increased recognition that these patients are out there. They present often at an academic medical center, and a lot of GI practices are seeing patients with this illness.

The purpose of the clinical practice update is that there is more information known now than there has been in the recent past. There was a clinical guideline for CVS diagnosis and management that I was a part of constructing in 2019, and even between 2019 and now, we've learned a little bit more about some of the comorbid conditions, some of the factors that predict outcomes to some degree, and there's been a little bit of innovation in terms of treatment, but not as much as we'd like, and that’s because we don't fully understand the underlying pathophysiologic basis of CVS. We’re limited in what we can do because of that, but the treatments we do have access to can be quite effective in most patients.

The impetus for the clinical practice update is to promote treatments that are very easily available to almost any clinician. They should be familiar with some of the therapies that can help the majority of patients they encounter. We have included a few clinical pearls about how to deliver some of the therapies that are designed to abort an attack and empower patients to have access to some tools they can turn to in order to truly “abort” the attack.

This clinical practice update also mentions the importance of lifestyle interventions. It's increasingly recognized that acute stress can trigger an attack, and that really highlights a whole set of behavioral therapies that could be used, including anything from mindfulness meditation and stress reduction techniques to addressing certain underlying illnesses like anxiety that may be highly comorbid with cyclic vomiting syndrome.

HCPLive Gastroenterology: Where do knowledge gaps still exist that need to be addressed?

Levinthal: There’s a lot that we don't know, and I think the future for cyclic vomiting syndrome is going to hinge on making some headway on the understanding of its pathophysiologic basis. There's some very interesting clinical associations with CVS that suggest a neurologic underpinning. It’s framed as a disorder of gut-brain interaction, but that doesn't say precisely what it is. In my mind, it likely is a central nervous system illness, and it doesn’t seem to be a coincidence that there is an increased rate of patients with migraine and even a slightly increased risk of having epilepsy. Those are 2 other episodic illnesses, and they have a neurologic basis. Most of the medications that we use for cyclic vomiting syndrome are also used to prevent or treat migraine. Even anti-seizure medications are a mainstay of treatment as well, so that just doesn't seem to be a coincidence.

I think the opportunity for the next line of research is to delve into some of the neurologic mechanisms, which is something I'm interested in studying. We have a small trial right now where we're looking at a neurologic factor that might be different in someone with cyclic vomiting syndrome compared to normal, healthy individuals, and that might be a biomarker of sorts. I don't want to get ahead of the science, but that seems to be a fruitful line to go down, because if we can uncover a neurologic mechanism, we could target that, and it might provide the basis for some additional therapies that have never been tried in cyclic vomiting syndrome. There are some newer medications for migraine, for example, that haven't been tested in cyclic vomiting syndrome patients, so that might be another opportunity. The future of treatment really hinges on understanding the illness better.

There are even some epidemiologic factors that we still don't understand. What predicts outcomes? What is the true healthcare utilization pattern? Where are patients showing up? Who is making those diagnoses? That really helps us understand how we could implement an education strategy in the medical field and get patients on front-line interactions with physicians.

All of those things, from implementation and healthcare initiatives to understanding the basic science of the illness to help devise new therapies, are huge opportunities that really could help a lot of patients.

Editors’ note: Levinthal has relevant disclosures with Takeda Pharmaceuticals and Mahana.

Reference

^{Brooks, A. Cyclic Vomiting Syndrome Clinical Practice Update Guides Diagnosis, Management. HCPLive. July 16, 2024. Accessed July 16, 2024. https://www.hcplive.com/view/cyclic-vomiting-syndrome-clinical-practice-update-diagnosis-management}