Crohn's disease is an inflammatory bowel disease that the inflammatory control response in the intestine gets in trouble. In patients with Crohn’s disease, the normal intestinal microflora passes through the intestinal mucosal layer and is exposed to the immune system, and various inflammatory substances are secreted, resulting in abdominal pain, diarrhea, and bloody stool. If the inflammation is severe, the intestine may be perforated. In this case, patients need emergency surgery to remove a part of the intestine.

Crohn’s disease is classified as a rare disease in Korea but the number of Korean patients with Crohn's disease has already exceeded the rare disease standard of 20,000.

According to the National Health Insurance Service, the nation had 25,532 Crohn’s disease patients in 2020. 

Korea Biomedical Review met with Professor Park Dong-il of Gastroenterology at Kangbuk Samsung Medical Center to learn everything about Crohn’s disease. 

More meat consumption, larger obese population associated with Crohn’s

Question: Why is the number of Crohn’s disease patients increasing rapidly in Korea?

Answer: Crohn's disease has been common in Europe and America since ancient times. It is a common disease in industrialized and prosperous countries. Also, this disease has a genetic predisposition. The Nod2 gene plays the role of a gatekeeper that recognizes the microorganisms in the intestine and discriminates between enemies and allies. If there is a mutation in this gene, it does not perform this role well.

As industrialization advanced in Korea, meat consumption increased and the obese population grew. Also, Koreans are more exposed to polluted environments such as air and water pollution. Due to these complex effects, Crohn’s disease cases are increasing and will expand further in the future.

Q: Many studies on Crohn's disease have been conducted. Are there any recent factors that are attracting more attention as the cause of this disease?

A: Most likely, an event such as exposure to antibiotics in a genetically predisposed person will change the composition of the gut microbiome. The gastrointestinal (GI) tract is exposed 24 hours a day to microorganisms and food components, with a thin vinyl-like membrane called the intestinal mucosa in between. Because of this, the gut microbiome plays a very important role.

The microbial composition in the GI tract in patients with Crohn’s disease and that in the general population is very different. The strains are different, and patients with the disease have a poor strain diversity. Let’s say the general population has about 1,000 kinds of intestinal microorganisms evenly distributed. But Crohn’s disease patients have only about 200 kinds, and one or two kinds occupy a very large part of the GI tract. So, only by checking the characteristics of intestinal microbes in feces, we can distinguish Crohn’s disease patients from the general population. 

Q: What are the advantages of early detection of Crohn's disease, and what should be done for early detection?

A: If Crohn's disease is diagnosed early, treatment can change the natural course of intestinal damage inflicted by inflammation. The longer the diagnosis is made, the longer the inflammation will last and the more difficult it will be to treat. The response to treatment is also rather slow. If the patient is diagnosed too late, the patient is exposed to a high risk of narrowing of the intestine or deep ulceration, resulting in a fistula.

The Korean healthcare system is better than that of the U.S. or Europe, so Crohn’s disease in local patients is found quite early. In the U.S. and Europe, the diagnosis is about one or two years late. But in Korea, it is eight to 10 months late, on average, because Korea offers good medical access allowing quick endoscopy and CT scans.

In Korea, there will be almost no person with stomach pain for more than a week who would delay visiting a hospital. For early detection, those with intestinal symptoms should go see a doctor at a hospital specializing in intestinal disorders. Do a simple exam or an endoscopy there, and if Crohn’s disease is suspected, the patient will be referred to a university hospital. If the symptoms last for more than two weeks, seeking professional medical help is the least painful method. 

About 60% of Korean patients with Crohn's disease have problems around the anus

Q: Are there any specific traits found in Korean Crohn's disease patients?

A: In Korean patients, there are many complications around the anus. This is a characteristic of Asian Crohn's disease patients. In fact, about 60 percent of Crohn's disease patients in Korea have a problem around the anus. In the West, that percentage is less than 20 percent.

It is still unknown why Asians have a high proportion of perianal complications.

Q: Drugs to treat Crohn's disease include anti-inflammatory drugs (sulfasalazine, mesalamine), steroids, immunomodulatory agents (azathioprine, purinethol), antibiotics (metronidazole, ciprofloxacin), biological agents (anti-TNF drugs, anti-interleukin agents, anti-integrin drugs). They have recently broadened treatment options. Treatment can be different depending on the severity, but how is the treatment carried out, and to what extent has the remission rate increased?

A: We use a Crohn’s disease activity index (CDAI) to score each patient for treatment. If inflammation subsides and symptoms improve, we call it remission with CDAI lower than 150. If CDAI is between 150 and 220, we call it mild activity, and between 220 and 450, moderate activity, and over 450, severe activity. We adjust treatment according to the score. 

People with severe Crohn’s disease receive steroids and immunosuppressive treatment from the beginning, and if there is no response within a month, we change the drug immediately. If the symptoms are not severe, we use low-cost, low-dose steroids. If there is no response to the first-line treatment, we use a second-line therapy, and if there is no response, a third-line treatment.

Even if the newest biological agents are very effective, each agent’s remission induction rate is only 60-70 percent. Some biological drugs show similar benefits whether they are used as the first-line or second-line treatment, but others work well in the first-line but not in the second-line. 

Q: Which patients with Crohn’s disease need surgery? What is the percentage of such patients?

A: If the intestines are clogged or have become hard, no matter how good the medicine is, it is useless. If the intestines are blocked, no matter what you eat, you vomit and suffer from severe stomach pain. In this case, surgery is performed to cut the intestines and then connect the normal intestines. Even if the intestine is ruptured due to severe inflammation, antibiotics should be given and surgery should be performed quickly.

There are some cases in which Crohn's disease was confirmed by a biopsy after surgery due to a ruptured intestine, but such cases are rare. At the time of diagnosis, more than 90 percent of patients are the inflammatory type. However, about 20 years after the diagnosis, only 10 to 20 percent are the inflammatory type, and 80 to 90 percent experience complications such as stenosis and fistula.

10-15% experience intestinal stricture, perforation, fistula, hemorrhage, and abscess 10 years after diagnosis

Q: How do you prescribe drugs such as steroids and immunosuppressants with a high risk of side effects to patients with Crohn's disease? 

A: We use steroids for Crohn's disease, but not for long. Compared to other countries, the amount used and the period of use are less in Korea. Domestic doctors are highly aware of the side effects of steroids, so they use them only when necessary for the shortest period of time.

Immunosuppressant medications have the risk of leukopenia and infection. In addition, the long-term use of immunosuppressants could form various malignant tumors, so we perform periodic screenings according to the guidelines. We do a blood test every six months and a CT scan every two years.

Beans, tofu, and white fish good for Crohn’s disease patients

Q: Patients with colorectal cancer due to Crohn's disease have also increased recently in Korea. What are the measures for early detection of colorectal cancer?

A: 10 years after the diagnosis, endoscopy from the anus to the end of the large intestine is performed at least once every two years, regardless of whether there are symptoms or not. In some cases, it is done every year if it has been diagnosed longer. For a closer examination during a colonoscopy, we spray some colors.

Q: After a diagnosis of Crohn's disease, how often should a patient get treatment?

A: About 80 percent of Crohn's disease patients should see a doctor every three months. Biological agents are administered at eight-week intervals, so treatment is performed accordingly. When inflammation is severe, treatment is given every two to three weeks, and when inflammation is not severe and long-term remission is maintained, treatment is given every six months.

Q: How should patients with Crohn's disease take care of their daily health?

A: The most important thing is to quit smoking. Smoking makes it difficult to treat Crohn’s disease. Patients should also stop drinking. Food intake is also very important. Patients should avoid fried foods, animal protein, and milk fat because they could cause the disease easily.

Of course, protein intake is also important. In particular, protein supplementation is important for those who lose a lot of protein due to diarrhea. Vegetable proteins such as beans and tofu are good. For animal protein intake, I recommend two eggs a day. It is also good to eat white fish. Hard vegetables, such as bracken, are rather harmful.

Patients should also avoid food that makes them sick if they eat it on a regular basis, and they should not eat certain foods such as chicken and pizza. The food that makes you sick is so different from person to person. Even the same food may have different symptoms depending on the additives. 

In Crohn’s disease, probiotics supplements are not effective. There are patients with Crohn's disease who absolutely need lactobacillus foods. In those cases, the attending physician uses it for a short period of time rather than a long period to improve intestinal symptoms. Therefore, it is recommended that you take probiotics after consultation with your doctor.

This article was originally published in Korea Healthlog, a sister paper of Korea Biomedical Review.  -- Ed.