Crohn’s disease (CD) and ulcerative colitis (UC) are two conditions commonly referred to as inflammatory bowel disease (IBD). Crohn's disease is an inflammatory bowel disease affecting different areas of the digestive tract in different people. Crohn's disease can be both painful and debilitating. It can also lead to life-threatening conditions, therefore, we need to understand what this disease is and how to treat it. 

What is Crohn's disease?

Crohn's disease is a transmural chronic inflammation that usually affects the distal ileum and colon but it can also affect any part of the gastrointestinal tract from mouth to anus.  

Transmural inflammation means that it is not only limited to the mucous membrane on the surface but also involves all layers of the intestinal mucosa, full-thickness. All layers are affected and inflamed, however, it is not continuous along the length of the intestine. 

The inflamed areas are in the shape of discontinuous segments of the intestine, a phenomenon called “skip areas”. 

This transmural spread typically leads to subsequent inflammation of the lymph system of these areas and subsequent thickening of the bowel wall and mesentery. 

The disease runs a relapsing and remitting course. Extensive inflammation may also lead to muscle enlargement, fibrosis, and strictures. The thing that can eventually lead to bowel obstruction. 

Crohn's disease can affect any region of the digestive system. About one-third of patients have small bowel involvement, particularly the terminal ileum, another 20% have solely colon involvement, and about 50% have both colon and small intestine involvement. There is no treatment, and most patients undergo remissions and relapses at random intervals. This illness has a negative impact on one's quality of life.

Epidemiology

Crohn's disease (CD) is most frequent in the Western developed world, particularly in North America, northern Europe, and New Zealand. Its incidence is bimodal, with onset most commonly occurring between the ages of 15 to 30 years and 40 to 60 years. It is more prevalent in cities than in rural regions.

Northern Europeans and Jews have a high incidence (incidence 3.2/1000), but Asians, Africans, and South Americans have a considerable uncommon occurrence. Recent investigations, however, have revealed a large increase in incidence in fast industrializing regions of Asia, Africa, and Australasia.

Approximately 30% of Crohn's disease patients involve the small bowel, mainly the terminal ileum, 20% include solely the colon, and 45% involve both the small bowel and colon. Crohn’s disease, which was once thought to be rare in pediatric and black populations, is now being detected in children of all ages and people of many ethnicities.

Cause of Crohn's disease

The exact cause of Crohn's disease is still unknown. Previously, doctors thought that an unhealthy diet and chronic stress are the leading causes. But now, doctors realized that these causes may aggravate but don’t directly cause Crohn's disease. 

Although the specific cause of inflammatory bowel disease (IBD) is unknown, there is strong evidence that the condition is caused by an improper immune response in the intestine to environmental stimuli such as medicines, toxins, infections, or intestinal bacteria in a genetically vulnerable host. 

For the immune system, doctors think that a bacterial or viral infection might trigger Crohn's disease. However, they didn’t identify the specific trigger yet. 

But they think that when your immune system tries to fight against an invading bacterium or organism, somehow, it also attacks the cells of your digestive tract. 

Another theory suggests that it might be genetically caused. Crohn's disease is more common in people who have a family member with the disease, so genes may play a role in the occurrence of this disease. 

Some other researches relate Crohn's to other factors, such as: 

• Smoking, which they found may double your chance of getting Crohn's. 
• Non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen. 
• Some antibiotics and birth control pills. 
• A high-fat diet might also increase the risk of getting Crohn's disease. 

Doctors also identified some risk factors related to a high incidence of getting Crohn's disease such as:

• Age. Crohn's can occur at any age but you are more likely to develop it when you are young as many patients have developed it below 30. 
• Family history. 1 in 5 Crohn's patients has a family member with the disease. Therefore, you are at a higher risk if you have a first-degree family member, a sibling, a parent, or a child with the disease. 
• Smoking. Smoking is one preventable risk factor. Smoking also has been related to a more severe form of the disease and a higher risk of surgery. 
• Non-steroidal anti-inflammatory drugs. Such as ibuprofen, naproxen, diclofenac sodium and aspirin. They don’t directly cause Crohn's but they make the bowel more inflamed which makes Crohn's worse. 

Crohn's Disease Genetic

Crohn's disease runs in families, so if you or a close relative has the condition, your family members are more likely to have it as well. According to studies, between 5% and 20% of persons with IBD have a first-degree family, such as a parent, child, or sibling, who also has one of the illnesses. 

Pathophysiology

Pathophysiology is complex, with genetic predisposition, infectious, immunological, environmental, and nutritional factors all playing a role. The distinctive transmural inflammation can affect the whole GI tract, from the mouth to the perianal region, although it most commonly affects the terminal ileum and right colon.

The first lesion appears as an infiltration around an intestinal crypt that leads to ulceration, which begins in the surface mucosa and progresses to deeper layers. Non-caseating granulomas grow as the inflammation proceeds, including all layers of the intestinal wall. It is characterized by cobblestone mucosa appearances at the affected intestinal segments while preserving normal sections of the mucosa called the skip areas. Scarring replaces the inflamed portions of the intestines when the Crohn's flare resolves.

Granuloma production is prevalent in Crohn's disease, although its absence does not rule out the diagnosis. Constant inflammation and scarring cause intestinal blockage and stricture development. Enterovesical, enteroenteral, enterocutaneous, and enterovaginal fistulas are also related to Crohn's disease.

Crohn's Disease Symptoms

Crohn's disease can involve any part of the digestive tract from mouth to anus. And it can involve different segments at the same time, it may also be confined only to the colon. 

Signs and symptoms range from mild to severe. They will come gradually, however, they may develop all of a sudden without a warning. Patients will also have times of remission, which means periods without any symptoms at all. 

Crohn's disease flare-ups are characterized by stomach discomfort (right lower quadrant), flatulence/bloating, diarrhea (which can include mucus and blood), fever, weight loss, and anemia. Perianal abscess, perianal Crohn’s disease, and cutaneous fistulas might be found in severe instances.

When the small intestine is compromised, symptoms such as diarrhea, malabsorption, weight loss, abdominal discomfort, and anorexia may occur. Pneumaturia, recurrent urinary tract infections, and feculent vaginal discharge can all be symptoms of an enterovesical fistula.

But when the disease is active, symptoms and signs include: 

• Fatigue.
• Fever.
• Diarrhea. 
• Blood in the stool. 
• Abdominal pain. 
• Cramping.
• Mouth sores. 
• Weight loss. 
• Reduced appetite. 
• Pain or drainage near and around the anus through a tunnel opens into the skin called a fistula. 

People with a severe form of the disease might also experience signs and symptoms that are not related to the digestive tract. Because the disease might be of an immunological origin, it might also attack other organs around the body. 

These symptoms include: 

• Inflammation of the skin. 
• Inflammation and redness of the eyes. 
• Anemia, iron deficiency, or inflammatory anemia.  
• Joint pain and inflammation. 
• Kidney stones. 
• Inflammation of the liver and bile ducts. 
• Delayed growth or delayed sexual development in children. 

Thromboembolic disease is now recognized as a prevalent Crohn's disease consequence. Deep vein thrombosis, stroke, or pulmonary embolism are all possible symptoms.

In all cases, the perineum must be inspected. Skin tags, ulcers, fistulas, scars, and abscesses may be discovered during the examination. Frank perforation is uncommon, however, it can be a symptom of Crohn's disease. Finally, another consequence of Crohn's illness is colon cancer.

So, if you are experiencing these signs or symptoms, don't hesitate and visit your general practitioner to be safe and start your treatment as soon as possible. Because the more you neglect your symptoms and your disease, the more complications you might develop. 

Crohn's Disease Eyes

Crohn's disease eye problems are typically minor. However, if not treated promptly, some varieties of uveitis can progress to glaucoma and even blindness. Maintain routine yearly eye exams and notify your doctor if you experience any eye irritations or vision difficulties.

Crohn's Disease Diagnoses

No single test is enough for your doctor to confirm the diagnosis of Crohn's disease. Your doctor will probably start by eliminating other possible causes. 

Stool examinations to rule out infections include direct examination and culture for parasite eggs, Clostridium difficile toxins, and white blood cell counts. Calprotectin testing in the stool helps diagnose active Crohn's disease, it is also used to monitor the disease.

A combination of tests will be used to determine whether the patient has Crohn's or not including: 

• Lab tests. 

Your doctor will ask for blood tests to check for anemia and other signs of infection. He or she will also ask for stool studies so they can test for blood cells or organisms in your stool sample.

Blood tests such as a complete blood count and a metabolic panel can detect anemia (B12 or iron deficiency) or liver illness. Normal anti-neutrophil cytoplasmic antibodies (ANCA) and increased anti-saccharomyces cerevisiae antibodies (ASCA) can distinguish Crohn's disease from ulcerative colitis. The degree of inflammation can be indicated by C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).

• Colonoscopy. 

This test allows your doctor to view the entire colon and the ileum, check for any fistulas or ulcers, take biopsies for lab analysis, and view granulomas. Granulomas are clusters of inflammatory cells, their presence confirms the diagnosis of Crohn's disease.

• Computerized tomography or CT. 

You may be asked to do a CT scan to view all your bowel and the tissues surrounding it. A special form of it is called CT enterography which specifically views your small intestine. 

• Magnetic resonance imaging or MRI. 

MRI might be needed particularly to evaluate fistulas around the anal canal.

Abscesses and fistulization can be detected with a computed tomography scan/magnetic resonance enterography (MRE) of the abdomen and pelvis. The decision between the two is made according to the location to be studied and is also motivated by the need to reduce radiation exposure in younger populations.

 Both provide a clearer picture of the damaged gut. When analyzing the fistulizing illness, an MRI might give greater detail in the pelvis.

• Capsule endoscopy. 

A new technique uses a capsule that has a camera on its end. You will be asked to swallow this capsule and it will take pictures of your intestine and transfer them to a recorder you will be wearing on your belt. Then your doctor will download the images from the recorder to a computer where he or she can check them for signs of Crohn's disease. This capsule will pass painlessly in your stool. This test is useful, but you may still need a colonoscopy to take biopsies from your colon. Besides, capsule endoscopy can’t be used in case of bowel obstructions, so it has its limitations. 

• Balloon-assisted enteroscopy. 

This test enables your doctor to look further into the small intestine where regular endoscopy can’t reach. This test is useful when capsule endoscopy shows signs and abnormalities that suggest Crohn's, but the diagnosis is still in question. 

Crohn's Disease Management

Patients with mild illness are often treated with 5-aminosalicylic acid (5-ASA), antibiotics, and nutritional treatment in a "step-up" strategy. If the patient does not react to this method, or if the condition is found to be more serious than previously anticipated, corticosteroid and immunomodulatory treatment with 6-mercaptopurine (6-MP) or methotrexate is tried. Finally, at the top of the therapy pyramid, biologic and surgical treatments are utilized.

Pharmacotherapy

Medications used in the treatment of Crohn disease include the following:

• 5-Aminosalicylic acid derivative agents (eg, mesalamine rectal, mesalamine, sulfasalazine, balsalazide)
• Corticosteroids (eg, prednisone, methylprednisolone, budesonide, hydrocortisone, prednisolone)
• Immunosuppressive agents (eg, mercaptopurine, methotrexate, tacrolimus)
• Monoclonal antibodies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, ustekinumab, vedolizumab)
• Antibiotics (eg, metronidazole, ciprofloxacin)
• Antidiarrheal agents (eg, loperamide, diphenoxylate-atropine)
• Bile acid sequestrants (eg, cholestyramine, colestipol)
• Anticholinergic agents (eg, dicyclomine, hyoscyamine, propantheline)

Surgery

Crohn's disease, unlike ulcerative colitis, has no surgical cure. The majority of Crohn's disease patients will require surgical intervention at some point in their lives.

The following surgical procedures may be used to treat the terminal ileum, ileocolic, and/or upper gastrointestinal tract:

• Resection of the affected bowel
• Ileocolostomy 
• Strictureplasty
• Bypass
• Endoscopic dilatation of symptomatic, accessible strictures

Surgical management of the colon may include the following:

• Subtotal or total colectomy with end ileostomy (laparoscopic or open approach)
• Segmental or total colectomy with or without primary anastomosis
• Total proctocolectomy or proctectomy with stoma creation

Biological Treatment

Biologics are immunoglobulins that have been designed to target certain cytokines or receptors involved in the inflammatory process. At the molecular level, each biologic agent targets a single location.

Anti-tumor necrosis factor (TNF). Alpha is a monoclonal antibody that can prevent TNF from causing inflammation in the body.

1. Examples of anti-TNF agents are infliximab, adalimumab, golimumab. 
2. Natalizumab and vedolizumab are two examples of adhesion molecule inhibitors. Vedolizumab is a gut-specific medication with less systemic adverse effects.
3. Many newer therapeutic agents for inflammatory bowel disease are in the pipeline.

Guidelines published by the American College of Gastroenterology for the management of Crohn's disease in 2018:

1. Avoid NSAIDs as they may exacerbate disease
2. Avoid smoking
3. Get mental health counseling as many patients develop depression
4. Sulfasalazine is effective for mild disease
5. Controlled ileal release Budesonide can be used to induce remission in people with a mild ileocecal illness.
6. Metronidazole should be avoided since it is ineffective in Crohn's disease.
7. Mild diarrhea can be managed with antidiarrheals
8. Thiopurines can be used for steroid-sparing
9. Anti TNFs can be used in patients resistant to steroids
10. Drain abscess radiologically if possible

Crohn's Disease Diet 

Dietician consultation and nutritional supplements are strongly advised before and throughout Crohn's disease therapy.

It might be difficult to determine which meals would best feed your body, especially if you have Crohn's disease or ulcerative colitis. Diet and nutrition are important aspects of living with inflammatory bowel disease (IBD), but no single diet works for everyone.

If you have Crohn's disease and have difficulty absorbing nutrition, it's critical to consume a high-calorie, high-protein diet even when you don't feel like it. In this situation, a successful Crohn's disease diet plan, based on professional suggestions, would emphasize eating regular meals plus two or three snacks each day.

This will help you acquire enough protein, calories, and minerals. You will also need to take any vitamin and mineral supplements prescribed by your doctor. You will be able to replace the nutrients in your body by doing so.

Certain foods should be avoided during an IBD flare, while others can help you acquire the correct quantity of nutrients, vitamins, and minerals without exacerbating your symptoms.

Your doctor may put you on an elimination diet, which requires you to forgo particular meals in order to determine which ones cause your symptoms. This method will assist you in identifying typical foods to avoid during a flare. Elimination diets should only be used under the direction of your healthcare team and a nutritionist to ensure that you are still getting enough nutrients.

Certain foods can cause cramps, bloating, and/or diarrhea. Many trigger foods should also be avoided if you have a stricture, which is a constriction of the intestine caused by inflammation or scar tissue, or if you have just had surgery. Certain meals are simpler to digest and offer your body with the nutrition it requires.

Differential Diagnosis

When evaluating a Crohn's disease patient, keep the following differentials in mind:

• Amebiasis
• Behcet disease
• Celiac disease
• Intestinal carcinoid
• Intestinal tuberculosis
• Mesenteric ischemia
• Ulcerative colitis

Crohn's Disease Complications

Crohn's disease might lead to many complications if left untreated, including: 

• Bowel obstruction. This is a serious issue. As we mentioned Crohn's affects the whole thickness of the intestinal wall. Over time, with chronic inflammation or the repeated attacks of inflammation, parts of the bowel will scar and narrow down which will, eventually, block the flow of the digestive tract content. 
• Ulcers. Chronic inflammation can lead to open sores or ulcers anywhere in your digestive system. 
• Fistulas. Sometimes ulcers can extend completely through the wall of the intestine perforating it and creating a fistula. A fistula represents an abnormal connection between different parts of the intestine. They usually develop around the anus. They can develop between different loops of the intestine where food will not be absorbed appropriately. They might also develop between loops of the intestine and the bladder of the vagina which is even worse because they will cause infection. Sometimes a fistula opens to the skin and drains intestinal contents through the skin. 
• Anal fistulas. The is the most common type of fistulas. It causes multiple infections and abscesses. 
• Malnutrition. Diarrhea, fistulas, and abdominal pain make it hard to properly absorb food which naturally leads to nutritional deficiencies such as iron deficiency anemia. 
• Colon cancer. Having Crohn's disease increases your risk of developing colon cancer that's why it is advised to follow up by a colonoscopy more frequently. 

For more information: See Colon Cancer Facts

• Blood clots. Crohn's might increase the risk of clots in your veins or arteries. 
• Other health problems. Crohn's disease can be associated with other symptoms like eye redness, joint pain, and kidney stones. These health conditions represent new problems with new complications. 

All these complications and escalated health problems can be prevented if the disease is diagnosed and treated early. 

Crohn's Disease Flare-up

Crohn's disease is commonly accompanied by remission and recurrence. The recurrence rate surpasses 50% in the first year following diagnosis, with 10% of individuals experiencing a chronic relapsing course. The majority of patients develop problems that necessitate surgery, and a considerable number of them experience postoperative clinical recurrence. At 5-year intervals after diagnosis, the chance of surgery is as follows:

• 5 years following diagnosis - The cumulative likelihood of having only one surgical operation is 37%; two or more surgical procedures, 12%; and no surgical procedures, 51%.
• 10 years following diagnosis - The cumulative chance of having only one surgical operation is 39%; having two or more surgical procedures is 23%, and having no surgical procedures is 39%.
• 15 years following diagnosis - The cumulative chance of having only one surgical operation is 34%; having two or more surgical procedures is 36%, and having no surgical procedures is 30%.

Patients with proximal small bowel illness are more likely to develop serious symptoms than those with ileal or ileocecal disease. The increased death rate might be attributed to Crohn's disease complications.

Crohn's Disease Prognosis

Crohn's disease is a chronic inflammatory disorder that progresses slowly. Appropriate medical and surgical therapy allows patients to live a normal life, with a favorable prognosis and an exceptionally low chance of death.

Several previous studies predicted a modest decline in life expectancy as a result of specific prognostic variables, such as female sex, extended disease duration, and disease location. Increased mortality was linked to lung cancer, genitourinary tract disorders, and GI, liver, and biliary diseases.

In contrast, several studies have found that people with Crohn's disease have a normal life expectancy. With the introduction of new medicinal therapy, population-based studies have revealed that overall survival for North American individuals with IBD is comparable to that of the US white population. The risk of mortality following Crohn's disease is therefore linked above all to gastrointestinal complications, to a malignant gastrointestinal tumor or to chronic obstructive pulmonary disease (COPD).

Interview

Today we have Doctor Lee who is a leading doctor at Hanyang University Hospital. He is going to discuss Crohn's Disease from an experienced medical point of view.

1. What is Crohn's disease?

Crohn's disease is when you keep getting ulcers in the esophagus, stomach, small and large intestines without knowing the exact cause. An ulcer develops and you get a hole in the intestine. Inflammation and ulcers develop without knowing the exact cause. So Crohn’s disease can affect all digestive functions. So, it can develop in the esophagus, stomach, small and large intestines, even the anus. So, in a way, it's one of the more troublesome illnesses.

2. What are the symptoms we should look out for, in the case of Crohn's disease?

It may slightly differ depending on where it occurs. The most common locations are the large intestine and small intestine. So, you can have a lot of diarrhea, because there is a wound. And you can see bloody stools. And the other thing is that because of the ulcers and lumps like this, the stomach can constantly hurt. And if that happens, you can lose a lot of weight. So, these symptoms can last for a long time.

And when the intestine explodes, there are cases of sudden pain in the stomach and other various symptoms. I think you can see such symptoms as representative symptoms.

3. In the case of Crohn's disease, are there any examinations we can do? And if it's actually Crohn's disease, what are the treatments we can do?

If you suspect Crohn's disease, it occurs in the stomach, esophagus, small and large intestines so you need to first see it through the endoscope. So, if there is such a lesion, it has to be done with a biopsy. And it may occur outside the intestine that is not visible through an endoscope.

In this case, you need to take a CT scan and see the whole structure inside the stomach. In addition, the inflammation level can rise in the blood level, so you can do a blood test that can reflect various levels of inflammation. You can judge all that and diagnose.

Treatment-wise, because we don’t know the cause, we can’t do a fundamental treatment. You need to know the cause to be able to do a fundamental treatment. So, for the treatment, you shoot various anti-inflammatory drugs that reduce inflammation. And because it is called our autoimmune disease, we can use drugs that suppress our body's immunity. And because there is inflammation, there are various drugs that suppress inflammation, so we usually use such drugs.

So those kinds of drug treatment come first, but if you have a hole in the intestine and the intestine is blocked even if you use these drugs, there is also a method to open the clogged area or the punctured area to perform surgery. So, first of all, drug treatment comes first, but if treatment is not available, surgery may be performed.

4. Is there any way to prevent Crohn's disease from the beginning?

I get this question asked a lot. Because we don’t know the cause, we cannot prevent it, either. But if you look at resources available till recently, it seems that food is quite important. It's probably better to avoid greasy foods, and research suggests that your gut bacteria play a very important role.

If we use antibiotics, our gut bacteria can die, right? But there are a lot of good bacteria in the intestines as well. Bacteria that we need. That's why gut bacteria are important in babies when they're young. There are many reports that kids who took a lot of antibiotics as a baby develop Crohn's disease later on. So, it's not good to take antibiotics when you're too young.

Another important thing is that when a mother has a baby, the microbiome in her belly goes to the baby as it is. That's why mothers shouldn't take antibiotics when they are pregnant. That is also being studied. So, in that respect, you have to be careful from a younger age.

Conclusion

According to Dr. Lee, Crohn's disease is an inflammatory bowel disease (IBD). It causes inflammation of the digestive tract. The organs most commonly affected by Crohn's disease are the small and large intestines, but it can affect any segment of the digestive tract, from the esophagus to the anus.

This disease can lead to abdominal pain, frequent diarrhea, fatigue, weight loss, and malnutrition. The cause is not yet known but it can be a very debilitating condition with constant inflammation and even fistulas.

In terms of disease diagnosis, it is important to use enteroscopy with biopsy to visually check and confirm the presence of disease. In addition, entero CT scans and MRIs, and blood tests can further aid in diagnosis.

Treatments are limited since the cause is not yet known. Nevertheless, there are anti-inflammatory drugs that give good results. In more severe cases, surgery may be performed to treat a bowel obstruction.

In terms of prevention, high-fat foods should be limited as well as the overuse of antibiotics at an early age as it is known that the intestinal flora can be damaged which can set up conditions for the development of Crohn's disease.

It is essential to educate patients about the nature of their disease. Patients should be screened for colon cancer whether or not they are receiving biological treatment.