Refractory Inflammatory Bowel Disease - Causes, Symptoms, Diagnosis and Treatment

Introduction:

Refractory inflammatory bowel disease represents a group of disorders of the intestine that can cause prolonged inflammation in the digestive tract. It has two main subdivisions of disease: ulcerative colitis and Crohn's disease.

• Ulcerative Colitis: It is a disease that causes inflammation of the mucosa (inner lining of an organ like the stomach) and ulcerations in the inner lining of the large intestine (colon).

• Crohn's Disease: It is a disease that will be present over a long period in the gastrointestinal tract, tending to spread anywhere from mouth to anus.

What Are the Symptoms of Ulcerative Colitis?

• Diarrhea with blood or pus.

• Bleeding in the rectum.

• Abdominal pain and cramps.

• The urgency to defecate.

• Fatigue.

• Fever.

• Weight loss.

What Are the Types of Ulcerative Colitis?

It is classified based on the location:

• Ulcerative Colitis: The primary sign of this condition will be bleeding from the rectum. Inflammation is confined to the area closest to the anus, where the rectum is located.

• Proctosigmoiditis: The area of inflammation is at the rectum and the lower end of the colon, also called the sigmoid colon. The symptoms include abdominal cramps and pain, and a strain to move the bowels, but they will pass a small amount of stool. This condition is called tenesmus.

• Left-sided Colitis: Inflammation extending from the rectum to the sigmoid and the descending portions of the colon. Abdominal cramping and pain on the left side, bloody diarrhea, and an urgent feeling to defecate.

• Pancolitis or Extensive Colitis: It affects the entire colon and causes severe bloody diarrhea, abdominal cramps, and pain, fatigue, weight loss.

What Are the Causes of Ulcerative Colitis?

The causes include:

• One possible cause would be hereditary. If any of the family members have this disease, it may also affect the next generation.

• Another possible cause would be an irregular response of the immune system. When an invading microorganism enters the body, the body's own immune system tries and fight against it, but unfortunately, it might affect the healthy cells in the digestive tract also, which may predispose them to this condition.

What Are the Risk Factors for This Condition?

The risk factor of ulcerative colitis includes:

• Hereditary: If the patient has a close family member who has this disease, there is a high chance of the individual getting the disease because of that.

• Age: It can occur at any age but is most commonly found in adults above 30 years of age.

• Race: White people and individuals of Jewish origin are at a higher risk for this disease.

What Are the Possible Complications That May Occur if One Has This Condition?

The possible complications include

• Bone loss which is also called osteoporosis.

• Severe bleeding and dehydration.

• Perforated colon.

• Toxic megacolon, which might tend to swell rapidly.

• High incidence of blood clots in blood vessels.

What Are the Diagnostic Methods Used for This Condition?

The possible diagnostic methods include:

• Endoscopy for Tissue Biopsy: In this procedure, a flexible tube with a lens and a light source at the tip is inserted via the anal opening to get inside the digestive tract, in which tissues are taken for analysis and sent to the laboratory.

• Colonoscopy: This procedure aids in viewing the entire colon on the inside using an endoscope.

• Blood Test: Blood tests are taken to check the level of blood in the patient's body and to analyze whether the patient has anemia (a condition where there are not enough red blood cells to carry adequate oxygen to the tissues and organs in the body). It is also taken to check for infection.

• Flexible Sigmoidoscopy: An endoscopy is done by inserting the flexible tube with a lens and a light source through the anus to examine the rectum and sigmoid colon, which is the lower end of the colon.

• Stool Sample: Specific proteins or white blood cells in the stool can be an indicative factor for ulcerative colitis.

• X-Ray: If the patient is symptomatic, an X-ray of the abdomen can be recommended by the doctor.

• Computed Tomography (CT): A CT scan of the abdomen will be prescribed to view the inside of the colon and to check for any inflammation.

What Are the Treatment Options for This Disease?

• Anti-Inflammatory Medications: It is the first line of options in treating this condition.

• Corticosteroids: It is used in the treatment of mild to severe forms of ulcerative colitis. Drugs like Prednisone and Budesonide are used. Since these corticosteroids work by suppressing the immune system, it has more side effects. So their use is limited for a short period.

• 5 Aminosalicylates: Olsalazine, Mesalamine, and Sulfasalazine are some examples.

• Immunosuppressants: Azathioprine and Mercaptopurine are some examples of this category

• Orally Delivered Agents: These are also called small molecules. These include Ozanimod and Tofacitinib. These medications make the patient more prone to shingles infection and blood clots. The U.S. (United States) food and drug administration has given a warning that patients who are taking this drug (Tofacitinib) are more prone to heart-related illnesses and cancer.

• Tumor Necrosis Factor (TNF) Inhibitors: These drugs work by acting on target proteins that are made by the immune system. Infliximab, Adalimumab, Golimumab, and Vedolizumab are examples of this category.

Symptomatic Management of This Condition Includes:

• Analgesics: They are also called pain relievers. Acetaminophen (Tylenol) can be prescribed. Ibuprofen (Advil) and Naproxen sodium are contraindicated since they may increase the severity of the disease.

• Iron Supplementation: Iron supplements are necessary if the patient has had intestinal bleeding for a long time since they will have an increased tendency to develop iron deficiency anemia due to loss of blood.

• Antispasmodics: These will be prescribed if the patient has cramps.

• Surgery: This is the last option if the medications are not effective. A surgical procedure called ''proctocolectomy'' is done. In this procedure, two major organs of the intestine, namely the colon and the rectum, are surgically removed. Without these organs, the poop will not come out, so the surgeon will create a pouch connecting the ileum and the anus through a J-shaped pouch. Either an ileostomy or colostomy is needed.

Risk Of Cancer:

Suppose the disease involves more than one organ, like the rectum. In that case, the patient is at an increased risk of getting affected by cancer. Thus a procedure called colonoscopy (a flexible tube called the colonoscope is inserted into the digestive tract with a lens and light source fitted to it to examine the interior parts of the colon and the rectum) must be performed as a part of cancer surveillance every one to two years. This type of procedure can be initiated if the condition is present for eight years or more. If the disease involves only the rectum, which is otherwise called proctitis, then the risk of cancer is low.

Another criterion for surveillance of cancer would be if at least one-third of the colon is inflamed, then the individual is at an increased risk for colorectal cancer. Most of the lesions of this type are generally visible, which makes it easier for biopsies. Targeted lesions can be taken for biopsy. Chromoendoscopy (dyes are instilled into the digestive tract to perform an endoscopy (an instrument consisting of a flexible tube and lens with a light source attached to it). Endoscopic resection is mostly recommended, and surgery is advised only if complete resection is not possible endoscopically.

Advancements in this procedure denote the use of a virtual endoscope as a potential part of endoscopic screening.

General Food Habits to Be Followed for Patients with Ulcerative Colitis:

It is not proven that what the individual consumes actually causes this condition. But limiting certain foods can help in controlling the aggravation of symptoms and signs caused by the consumption of certain foods.

• Limitation of Dairy Products: Being lactose intolerant (an individual's body cannot digest milk sugar in dairy products) can worsen the symptoms. Lactaid can be used to reduce the symptoms. Some patients reported that other symptoms, such as diarrhea and abdominal pain, were reduced by limiting the intake of dairy products.

• Increase the Intake of Liquids: Have adequate amounts of water on a regular basis. Avoid the intake of alcohol and beverages because they contain high amounts of caffeine which aggravates the symptoms. Carbonated drinks produce gas.

• Regular Exercise: This will help in reducing stress and muscle fatigue. It also helps in easy digestion and regulating bowel function.

Crohn's Disease:

It causes inflammation and swelling in the digestive tract and can affect any part of the digestive tract. It most commonly affects the small intestine and colon.

What Are the Symptoms of Crohn's Disease?

The symptoms of Crohn's disease include:

• Cramps in the abdomen.

• Fever.

• Fatigue.

• Weight loss.

• Diarrhea.

• Bloody stool.

• Red tender bumps on the skin.

More severe symptoms as the disease progress include:

• Perianal fistula (a small tunnel that develops between the skin and the anus).

• Formation of ulcers anywhere between mouth and anus.

• Occurrence of anemia which causes general body weakness.

• Malnutrition is due to a lack of not getting the right amount of nutrients.

• Obstruction or blockage in the intestine.

What Are the Causes of This Condition?

The exact cause of this condition is unknown, but family history or autoimmune disease can be a cause.

According to Crohn's and Colitis Foundation (CCFA), 20 % of individuals having Crohn's disease also have a family history.

The autoimmune disease causes the body's own immune system to affect the cells in the body. Though one of the causes of Crohn's disease is autoimmune, it has not been proven, so this condition does not fall completely under the category of autoimmune disease.

How Can This Disease Be Diagnosed?

• A thorough medical history and family history

• A physical examination checking for bloating in the abdomen.

• Checking for abnormal sounds in the abdomen using a stethoscope.

• Tapping the abdomen to check for tenderness and pain and to check if the liver or spleen is enlarged.

• Stool test.

• Blood test.

• Colonoscopy: A long flexible tube with a lens and camera attached to it is inserted into the rectum to check for any changes inside it.

• Upper Gastrointestinal Tract Endoscopy: A tube is inserted with a lens and a light source to see inside the mouth, esophagus, stomach, and small intestine.

• Barium Swallow Test Along With X-Ray: This will help in visualizing the internal organs more clearly.

• Computerized Tomography: It helps in inspecting the inside of the bowel more clearly

• CT Enterography: This technique works by drinking a contrast liquid material and then taking a scan to view the bowel. This helps in providing more accurate images of the bowel and has even replaced barium X-rays in many healthcare centers.

• Magnetic Resonance Imaging: This technique uses magnetic fields and radio waves to create clear images of tissues and organs.

• Balloon-Assisted Enteroscopy: In this technique, a scope is used along with a device called the overtube (a sleeve-like instrument made of semi-rigid plastic). This is especially useful when normal endoscopes cannot go deep inside the bowel. This will also be useful when normal endoscopy shows abnormalities but cannot arrive at a definitive diagnosis.

• Capsule Endoscopy: A capsule with a camera is given to the patient and asked to swallow it. This little camera then would take pictures of the small intestine and send them to a recorder that would have got attached to a belt that the patient would wear. These captured images are then downloaded to a computer and viewed to check for any signs of the disease. The camera then exits the patient's body through the stool. This method is contraindicated if there is an obstruction in the bowel. An endoscopy and a biopsy are still needed to confirm the diagnosis of Crohn's disease.

What Are the Possible Treatments for This Condition?

There is no possible cure for Crohn's disease, but treating the symptoms will help in reducing the severity of the disease.

• Medications: Anti-inflammatory drugs containing 5 aminosalicylic acids like Sulfasalazine, Balsalazide, Mesalamine, and Olsalazine are the first line of drugs that are often used in the treatment of Crohn's disease.

• Corticosteroids: Drugs such as Prednisone and Budesonide can aid in reducing inflammation.

• Immunosuppressants: These drugs reduce inflammation by targeting the substances present in the immune system that cause inflammation. Sometimes a combination of these drugs works better than taking one drug at a time. Examples include Azathioprine and Mercaptopurine. Possible side effects of these drugs include lowered resistance to infection, inflammation of the liver, vomiting, and nausea. Methotrexate can be used if other drugs do not respond well.

• Antibiotics: Drugs such as Ciprofloxacin, Metronidazole work by reducing the harmful bacteria which may be causing inflammation in the intestine. This class of drugs also has the capacity to reduce the drainage from fistulas and abscesses, which can sometimes heal by using these drugs regularly.

• Tumor Necrotizing Factor (TNF) Inhibitors: Some examples of TNF include Infliximab, Adalimumab, and Certolizumab pegol.

• Vedolizumab: This drug works by stopping certain molecules called integrins which are present in the immune system, from binding to other cells present on the intestinal walls. This drug is a gut-specific agent and is an approved drug for use in patients suffering from Crohn's disease.

Other drugs can also be used to reduce the signs and symptoms of the disease.

These kinds of drugs include:

• Antidiarrheal drugs: Fiber supplements like psyllium powder (Metamucil), Methylcellulose can help in relieving mild to moderate diarrhea by adding volume to the stool. In cases of severe diarrhea, Loperamide can be used.

• Analgesics: Otherwise known as pain relievers. An example includes Acetaminophen (Tylenol) can be used to relieve pain. Drugs such as Ibuprofen (Advil, Motrin IB) are contraindicated because of their tendency to worsen the symptoms of this disease.

• Vitamins and Mineral Supplements: They can be prescribed if the patient has malnutrition.

• Nutrition therapy: The doctor can recommend a special diet that can be given by mouth or feeding tube or via veins (parental nutrition) if the patient has Crohn's disease. This can give rest for the bowel and improve overall nutrition. This therapy is specifically useful when combined with other medications like immunosuppressants. Parenteral nutrition is recommended prior to surgery or when other medications do not control the symptoms well.

• Low-Fiber Diet: The doctor can also prescribe a low-fiber diet to reduce the risk of blockage in the intestine if the patient has a narrow bowel.

• Surgery: Performing surgery does not completely cure this disease since it tends to recur after a while. Surgery is recommended when other methods like medications, lifestyle changes, and nutrition supplements do not work out. While doing the surgery, the infected portion of the digestive tract is generally cut off and reconnected to the healthy portion. This method is effective in closing abscesses (a painful collection of pus caused by an infection) and fistulas (an abnormal connection between two parts of the body). One good option would be taking medications along with surgery.

Conclusion:

Though the cause of inflammatory bowel disease remains unknown, the right modifications in diet and adopting a healthy lifestyle along with taking medications will positively impact reducing the severity of the disease. With recent advancements in technology, diagnosis of the disease has been made easy. Even though surgery cannot completely cure this disease, combining it with medications and proper nutrition supplements can help in reducing its recurrence.