Cyclic vomiting syndrome not well understood

Patients can go years without a diagnosis or effective treatment

By Markian Hawryluk / The Bulletin / @markianhawryluk

When Maren Nelson was looking for a health care improvement project for her doctoral work in nursing practice, she learned of a group of patients that had stymied local emergency department providers.

“The ED staff was quite frustrated with this particular population of patients who show up several times in a relatively short period of time with this intractable nausea and vomiting which would respond to nothing,” the nursing professor at Central Oregon Community College said.

The staff would run diagnostic test after test, all coming back normal, yet patients continued to vomit. Doctors could treat them with anti-nausea and pain medications to lessen their symptoms, but couldn’t tell the patients what was causing their illness. Within weeks, the patients would be back vomiting in the ED again. The emergency medicine doctors were stumped and began to wonder whether the patients were just there seeking narcotics.

“These are people who keep vomiting over and over again and don’t have an established diagnosis,” said Dr. Gillian Salton, medical director for Central Oregon Emergency Physicians, the ED doctors at St. Charles Bend. “Everybody gets frustrated. The patient wants to know what’s wrong with them. We can’t tell them what’s wrong with them. We end up doing the same nonproductive testing over and over and over again.”

The patients had a little-known condition named cyclic vomiting syndrome, characterized by bouts of prolonged, intense vomiting that occur every few weeks or months, interspersed with periods of normal health. The disorder has been long diagnosed in children, but only recently recognized in adults.

Emergency rooms throughout the nation see scores of CVS patients, but with little awareness of the condition, patients are often sent home without a diagnosis or appropriate treatment.

Now Nelson and the emergency room physicians at St. Charles Bend are collaborating on an effort to better identify and treat CVS patients. They are standardizing diagnosis and treatment protocols, and connecting patients with doctors who can help prevent vomiting episodes or abort them quickly when the cycle starts. If the effort is successful, it could easily be rolled out to the three other hospitals in the St. Charles network, and possibly to other hospitals across the country.

Moreover, it could for the first time tell patients in miserable condition with a horrible quality of life what is happening to them.

A miserable disease

Cyclic vomiting syndrome is much more than your garden-variety stomach bug. Patients can have episodes at any time, but they often start early in the morning, resulting in relentless nausea and repeated bouts of vomiting or retching. Patients are often pale and listless, and can experience severe abdominal pain. Symptoms can continue for days if untreated. Patients often require emergency room or hospital care to stop the vomiting and to address severe dehydration. Patients have been known to vomit so long and violently that they damage their esophagus.

Kristina McDiarmid, 21, of Eugene has had CVS since age 2. Her episodes would occur about once a month and were so severe that she was routinely hospitalized throughout her childhood. She was finally diagnosed at the age of 7 and has standing orders for admission at the pediatric ward of her local hospital.

During one episode, a doctor tried a combination of the sedative Ativan and Compazine, an antipsychotic often used to treat migraines. The combo worked and has since become her standard treatment. McDiarmid has also learned that stress or excitement can trigger her vomiting episodes.

“My family lives in Canada, and we try to go there once a year, and every time I try to go there, I get sick,” she said. “Every Christmas I’ve been hospitalized or I’ve been sick at home. I still look forward to it, but it’s really disappointing because I miss the holiday and all the fun.”

A CVS diagnosis requires at least three such vomiting episodes within a 12-month period, interspersed with periods of no nausea or vomiting whatsoever, and the absence of any other factors that could explain the vomiting.

Without a billing code for the diagnosis, Nelson and the ED docs used the diagnosis criteria to get a better handle on how many CVS patients were coming to the hospital in Bend. Out of 30,000 ED visits in Bend over 12 months, about 10 percent of patients had symptoms of nausea and vomiting. They eliminated patients whose vomiting had been linked to pancreatitis, appendicitis or other diagnosed conditions, and then looked at how many of the remaining patients had visited the ED at least three times. They were stunned to find 116 potential CVS patients.

“It’s insane for the size of this community,” Nelson said. “That represents a fairly healthy chunk.”

As Nelson sought to learn how to better manage these patients, she reached out to the Cyclic Vomiting Syndrome Association, whose founder, Kathleen Adams, happened to be born and raised in Bend.

Adams’ daughter Molly had her first vomiting episode at 18 months, then a second six months later. Soon she settled into a pattern of vomiting episodes every six to eight weeks.

“Her typical pattern for 11 years undiagnosed — she would wake up in the morning and be the color of her bedsheets and want to be flat,” Adams said. “She would start vomiting every five to 10 minutes for several hours. She might sleep for an hour, wake up and start the process again.”

The entire episode would go on for an average of two to three days. Before Adams learned how to interrupt the cycle, Molly would be admitted to the hospital every six to eight weeks for more than a decade.

“Standing over the bed of a child who is retching and vomiting and that miserable for that long, and that often changes a family dynamic in a big way,” she said.

In 1991, Adams, a nurse by training, came across a letter to the editor in a pediatric medical journal describing cyclic vomiting syndrome. That led her to Dr. David Fleisher, the grandfather of CVS research. Adams took Molly to Columbia, Mo., to see Fleisher, and on the morning of their appointment, her daughter started vomiting.

“That was the only time I’ve ever been grateful for an episode,” Adams said.

Fleisher immediately diagnosed Molly with CVS and prescribed amitriptyline, an old anti-depression medication that has been shown to reduce the frequency and severity of CVS episodes.

With inroads into the medical community — her husband was on the faculty at the Medical College of Wisconsin — Adams began to push clinicians to research CVS, to standardize diagnosis criteria and to find new treatments. In 1993, she established the nonprofit association, which now boasts more than 800 members.

Over the next few years, Molly’s episodes decreased. Stress and excitement were frequent triggers, making birthdays and holidays a challenging time. The family routinely traveled on vacation with an IV pump.

Like many other pediatric CVS patients, her vomiting episodes gradually transformed into recurrent migraine headaches in late adolescence. At age 36, she still relies on the amitriptyline to keep her condition in check. But a turbulent flight over the Rocky Mountains from Denver to her family’s home in Durango can still set off a recurrence.

The association has now held multiple scientific conferences about the condition and helped to published research in medical journals. Still, 20 years after Molly went a decade without a diagnosis, other CVS patients still find themselves in the same boat.

“There are no markers for it, there’s not a blood test, there’s not an X-ray. The history can be so wide and varied, all the way from somebody who has an episode three times a year to somebody like Molly (with an episode every six weeks),” Adams said. “All those factors put it in the cracks of the floorboards of medicine.”

Surveys suggest that up to 2 percent of children might have CVS, numbers so high that even Adams finds them hard to believe. There are no good estimates of how many adults might have the condition.

“I can tell you when I was taking Molly to the hospital time after time, I felt like I was the only one in the world that was dealing with this,” Adams said.

Unraveling clues

While pediatric patients can lean on their parents and pediatricians, the condition often leaves adults with little help or support. Their repeating vomiting episodes can carry all the consequences of bulimia: profound weight loss, damage to teeth and throat, and frequently, social isolation.

“What happens aside from sickness itself, there are significant socioeconomic effects,” said Dr. Thangam Venkatesan, an associate professor of medicine at the Medical College of Wisconsin, who has come to specialize in CVS cases. “All of this becomes extremely difficult and places a huge burden on patients. They have a terrible quality of life.”

Many CVS patients lose jobs or drop out of college, unable to overcome the repeated episodes of vomiting that leave them essentially disabled if not hospitalized for days at a time. Marriages and relationships suffer when one partner is constantly sick.

“The problem is there’s only a handful of physicians, people in the academic community mostly, who are somewhat aware of this diagnosis,” Venkatesan said. “You have to rely on your age-old skills of taking a history and coming up with a diagnosis.”

Researchers have identified some genetic mutations that are associated with CVS, but no smoking guns. Many pediatric patients have been shown to have a defect in their mitochondria, the energy-producing portion of their cells. Mitochondria is passed down along maternal lines, and genetic charts have shown for some CVS patients a maternal family history of other disorders that may be related to mitochondrial issues as well. But more research is needed to conclusively point to mitochondrial dysfunction as the cause of CVS, much less to begin to develop cures or treatments for it.

“If you look at the literature, a lot of people undergo millions and millions of investigations, which I think are futile,” Venkatesan said. “One in five patients actually have surgery for it, like their gallbladders taken out, which is a pretty drastic step and it does nothing to relieve their symptoms.”

Venkatesan has found, however, that once patients are diagnosed with CVS, there are treatments that help.

One study found tricyclic antidepressants, such as amytriptaline, on average, reduced the frequency of CVS episodes per year from 18 to five, cut the duration of the episodes from a week to three days, and cut the number of ED visits from 15 to four. Some patients also respond to epilepsy medications and certain supplements. Migraine treatments and other drugs can help to abort the episode in its initial stages. Most CVS patients can feel when an episode is about to start. Once the vomiting starts, however, there is often little that can be done other than to treat the symptoms.

“Essentially, the horse is out of the barn and then it’s just supportive therapy, get the patient comfortable,” Venkatesan said. “All you can do is take care of them.”

Patients can be given IV fluids to prevent dehydration, anti-vomiting medications and sedatives. If the patient can be put to sleep, Venkatesan said, the vomiting will stop.

Some 85 percent of patients respond to treatment to prevent or reduce the number of episodes. And that makes it all the more important for doctors to recognize the condition. A recent survey of CVS patients, however, found that 89 percent of adults presenting with CVS in the ER left without a diagnosis. And perhaps more worrisome, 30 percent left without a referral to a specialist. Adults in the survey averaged 15 emergency room visits due to vomiting and had gone to four or five different EDs with their symptoms.

“Many of these patients are just bouncing into the emergency room all the time. Many times, they aren’t being diagnosed,” said Dr. Harald Schoeppner, a gastroenterologist at Legacy Mt. Hood Medical Center in Gresham. “This episodic nature makes it very hard to care for them.”

Schoeppner said most gastroenterologists care for at least one or two CVS patients in their practice, and they’re often very difficult cases to manage.

“The big thing is to teach the patient that they have this, that they’re not crazy or they’re not doing it to themselves. Validation is really a big point,” he said. “They can come in with the diagnosis, and then you get treated differently by other doctors, like a genuine diagnosis, and not just treated as malingering or drug seeking.”

Life interrupted

In Bend, Nelson and the emergency physicians are hoping that more of the local patients can get a diagnosis and a care plan. They have embedded protocols for diagnosis and treatment into the electronic health records, helping doctors to identify those cases when they come in and know what medications are most effective. Then care managers will follow up with patients after the discharge to ensure they get a prevention plan in place and have medications to abort emerging episodes.

Nelson hopes that, over time, the new protocols will help patients better manage their CVS and keep them out of the emergency room. With the costs of a single ED visit for CVS at $2,880, the savings to patients and the health care system would be tremendous.

The pot link

There is, however, an emerging concern about a link between CVS and chronic marijuana use. Some 40 percent of CVS patients have reported using cannabis, and clinicians have identified a separate condition, known as cannabinoid hyperemesis syndrome, that causes prolonged vomiting in those who smoke marijuana every day.

“It’s a little bit of a chicken-and-the-egg piece, because many people say the marijuana helps their nausea feel better,” Salton said. “But in some cases, it seems like the cyclic vomiting doesn’t start until people become daily marijuana users.”

Andrew Trompeter, 27, of Medford has lived with CVS for several years.

Trompeter said sometimes marijuana is the only thing that keeps his nausea and vomiting in check and allows him to eat. His doctor has suggested he get a medical marijuana card.

Trompeter was scheduled to travel to Bend this month to get more advice about his condition from Dr. Glenn Koteen, a local gastroenterologist who is listed on the CVS website. Koteen has a number of CVS patients, mostly in their early 20s, often with significant anxiety or depression due to difficult life circumstances.

“It’s hard to treat their nausea and vomiting as a symptom, if you don’t treat the trigger which is depression, anxiety and stress,” he said.

Yet many of these patients have had limited access to health care, much less to mental health services. Many self-medicate with marijuana as much for the stress relief as for their nausea.

“They take it to feel better. They take it to treat their anxiety, their depression, their stress. They take it because it helps them sleep,” Koteen said. “And when you tell them, ‘You have to stop this for a month to see if the process starts to get better,’ they look at you like you’re crazy, and they’re reluctant because obviously the marijuana is helping them versus causing this.”

A lack of awareness about CVS, inconsistent patient hand-offs between providers, limited access to care and poor patient compliance all make CVS a challenging disease.

While some of those hurdles may be beyond the scope of local providers or CVS advocates to overcome, efforts like those in Bend can at least begin to give patients a starting point for seeking help.

“These things have not been understood well for a long time, and a lot of them have been told they’re drug seeking, they’re anxious, it’s all in their head. The same things people heard about migraines,” Salton said. “So (it’s important) to have some validation that everybody who told them that was wrong.”

—Reporter: 541-617-7814, mhawryluk@bendbulletin.com