Crohn’s Disease Diagnosis, Treatment, Prevention

Crohn’s Disease Diagnosis/Crohn’s disease is a chronic long-term type condition of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus. It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. Crohn’s disease, also called ileitis or enteritis, can affect any part of the gut, from the mouth all the way down to the anal.

Crohn disease (CD) and ulcerative colitis (UC) are two conditions commonly referred to as inflammatory bowel disease (IBD). They are immunologically mediated inflammatory diseases of the gastrointestinal tract. In CD, the inflammation extends through the entire thickness of the bowel wall from the mucosa to the serosa. The disease runs a relapsing and remitting course. With multiple relapses, the CD can progress from an initially mild to moderate inflammatory conditions to severe penetrating (fistulization) and/or stricturing disease.[rx][rx][rx][rx]

Types of Crohn’s Disease

The following are five types of Crohn’s disease,

Ileocolitis

• The most common form of Crohn’s, ileocolitis affects the end of the small intestine (the ileum) and the large intestine (the colon). Symptoms include diarrhea and cramping or pain in the right lower part or middle of the abdomen. This type is often accompanied by significant weight loss.

Ileitis

• This type affects only the ileum. Symptoms are the same as ileocolitis. In severe cases, complications may include fistulas or inflammatory abscess in the right lower quadrant of the abdomen.

Gastroduodenal Crohn’s disease

• This type affects the stomach and the beginning of the small intestine(the duodenum). Symptoms include loss of appetite, weight loss, nausea, and vomiting.

Jejunoileitis

• This type is characterized by patchy areas of inflammation in the upper half of the small intestine (the jejunum). Symptoms include mild to intense abdominal pain and cramps following meals, as well as diarrhea. In severe cases or after prolonged periods, fistulas may form.

Crohn’s (granulomatous) colitis

• This type affects the colon only. Symptoms include diarrhea, rectal bleeding, and disease around the anus (abscess, fistulas, ulcers). Skin lesions and joint pains are more common in this form of Crohn’s than in others.

Causes of Crohn’s Disease

• Immune system – It’s possible that a virus or bacterium may trigger Crohn’s disease. When your immune system tries to fight off the invading microorganism, an abnormal immune response causes the immune system to attack the cells in the digestive tract, too.
• Heredity –  Crohn’s is more common in people who have family members with the disease, so genes may play a role in making people more susceptible. However, most people with Crohn’s disease don’t have a family history of the disease.
• Age – Crohn’s disease can occur at any age, but you’re likely to develop the condition when you’re young. Most people who develop Crohn’s disease are diagnosed before they’re around 30 years old.
• Ethnicity – Although Crohn’s disease can affect any ethnic group, whites and people of Eastern European Jewish descent have the highest risk. However, the incidence of Crohn’s disease is increasing among blacks who live in North America and the United Kingdom.
• Family history – You’re at higher risk if you have a close relative, such as a parent, sibling or child, with the disease. As many as 1 in 5 people with Crohn’s disease has a family member with the disease.
• Cigarette smoking – Cigarette smoking is the most important controllable risk factor for developing Crohn’s disease. Smoking also leads to more severe disease and a greater risk of having surgery. If you smoke, it’s important to stop.
• Nonsteroidal anti-inflammatory medications – These include ibuprofen, naproxen sodium, diclofenac sodium, and others. While they do not cause Crohn’s disease, they can lead to inflammation of the bowel that makes Crohn’s disease worse.

Foods that may cause problems include

• Fatty or fried foods
• genetic factors
• The individual’s immune system
• Smoking
• Previous infection
• Environmental factors
• Spicy foods
• Dairy
• High-fiber foods
• Raw or dried fruit and vegetables
• Seeds
• Nuts

Symptoms of Crohn’s Disease

• Ulcers are raw areas in the gut that may bleed. If they do bleed, the patient might notice blood in their stools.
• Mouth ulcers – these are a common symptom.
• Diarrhea – that can be range from mild to severe. Sometimes there may be mucus, blood, or pus. The patient may get the urge to go but find nothing comes out.
• Fatigue – individuals often feel extremely tired. Fever is also possible during fatigue.
• Altered appetite– may be the time when the appetite is very low.
• Inflammation of the skin, eyes, and joints
• Inflammation of the liver or bile ducts
• Abdominal pain and cramping
• Blood in your stool
• Mouth sores
• Reduced appetite and weight loss
• Pain or drainage near or around the anus due to inflammation from a tunnel into the skin
• Anemia due to – loss of blood can lead to anemia.
• Rectal bleeding and anal fissures – the skin of the anus become cracked, leading to pain and bleeding.
• Persistent Diarrhea
• Rectal bleeding
• Urgent need to move bowels
• Abdominal cramps and pain
• The sensation of incomplete evacuation
• Constipation (can lead to bowel obstruction)
• uveitis (eye inflammation)
• skin rash and inflammation
• liver or bile duct inflammation
• delayed growth or sexual development, in children
• Fever
• Loss of appetite
• Weight Loss
• Night Sweats

Diagnosis of Crohn’s Disease

Crohn’s disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn’s disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn’s disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). [rx]

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History and Physical

Patients with flare-ups of Crohn’s disease typically presents with abdominal pain (right lower quadrant), flatulence/bloating, diarrhea (can include mucus and blood), fever, weight loss, anemia.

In severe cases, perianal abscess, perianal Crohn’s disease, and cutaneous fistulas can be seen.

Crohn’s disease is associated with extraintestinal manifestations including episcleritis, uveitis, stomatitis, aphthous ulcers, liver steatosis, gallstones, cholangitis, primary sclerosing cholangitis, nephrolithiasis, hydronephrosis, urinary tract infections, arthritis (spine – sacral, knee, ankles, hips, wrist, elbows), ankylosing spondylitis, erythema nodosum, and pyoderma gangrenosum.

Treatment of Crohn’s Disease 

The medical treatment is broadly grouped into two classes

• Mild to moderate disease – can be treated by oral mesalamine, immunomodulators such as thiopurines (mercaptopurines, azathioprine), methotrexate, and steroids.
• Moderate to severe disease – (including fistulizing disease) will be best treated using a combination of immunomodulators and biologics (infliximab, adalimumab, golimumab, vedolizumab) or biologics alone.
• Antibiotics – may be used when infections—such as abscesses—occur in Crohn’s disease. They can also be helpful with fistulas around the anal canal and vagina.  Antibiotics used to treat bacterial infection in the GI tract include metronidazole, ampicillin, ciprofloxacin, fistulas, strictures, or prior surgery may cause bacterial overgrowth. Doctors will generally treat this by prescribing ampicillin, sulfonamide, cephalosporin, tetracycline, or metronidazole others.[5]
• Anti-inflammation drugs – the doctor will most likely start with mesalamine (Sulfasalazine), which helps control inflammation.
• Corticosteroids – Prednisone and methylprednisolone help treat the inflammation in moderate or severe Crohn’s disease by helping to suppress the body’s immune system. Because they can trigger both short- and long-term effects, people shouldn’t use them continuously.
• Immunosuppressant drugs – these drugs reduce the patient’s immune response. The doctor may prescribe 6-mercaptopurine or a related drug, azathioprine. Side effects include vomiting, nausea, and a weaker resistance to infection.
• Cyclosporine for treatment of active Crohn’s disease – The results of this review demonstrate that low dose oral cyclosporine is not effective for the treatment of active Crohn’s disease. Studies indicate that Crohn’s patients treated with a low dose (5 mg/kg/day) oral cyclosporine could experience side effects including kidney problems. Therefore the use of this medication for the treatment of chronic active Crohn’s disease is not advisable. Higher oral doses and injections of cyclosporine have not been sufficiently evaluated. Larger doses of cyclosporine are not likely to be useful for the long‐term management of Crohn’s disease due to the risk of kidney damage and the availability of other proven medications.
• Thalidomide for induction of remission in Crohn’s disease – Crohn’s disease is a chronic inflammatory disorder of the bowel. Thalidomide may help to reduce inflammation in the gut and might be effective for the treatment of Crohn’s disease. One randomized controlled trial on the use of thalidomide for the treatment of active Crohn’s disease (and ulcerative colitis) in children is in progress and should be completed in 2011.
• One randomized controlled trial using lenalidomide –  a drug similar to thalidomide, was identified. This relatively small but well-designed study did not demonstrate a benefit for lenalidomide treatment of active Crohn’s disease. Patients treated with high dose lenalidomide (25 mg/day) were more likely than patients receiving placebo (fake drug) to experience side effects. Side effects in the study included a headache, rash, and nausea. Known side effects of thalidomide include severe birth defects. The use of thalidomide or lenalidomide for the treatment of active Crohn’s disease is not recommended.
• Interleukin 10 (IL‐10) for induction of remission in Crohn’s disease – Crohn’s disease is an inflammatory condition of unknown origin that can affect any portion of the gastrointestinal
• Mercaptopurine  & Azathioprine –  shown here in tablet form, is a first line steroid-sparing immunosuppressant
• Azathioprine and 6-mercaptopurine (6-MP) – are the most commonly used immunosuppressants for maintenance therapy of Crohn’s disease. They are purine anti-metabolites, meaning that they interfere with the synthesis of purines required for inflammatory cells. They have a duration of action of months (slow-acting). Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses.
• Aminosalicylates (5-ASA) – Usually prescribed for people with a mild or moderate type of Crohn’s, these medications—which include sulfasalazine, mesalamine, olsalazine, and balsalazide— work by decreasing inflammation in the lining of the GI tract. Although they aren’t specifically approved by the Food and Drug Administration (FDA) to treat Crohn’s, they can help prevent a flare-up, according to the Crohn’s & Colitis Foundation.
• Immunomodulators – If aminosalicylates and corticosteroids haven’t helped quell the inflammation, doctors may prescribe immunomodulators, including 6-mercaptopurine (6-MP), azathioprine, cyclosporine, and methotrexate. These medications also work by suppressing the immune system and may take several weeks or months to start working.
• Biologics – For people who haven’t responded to other forms of Crohn’s disease treatment, doctors may prescribe newer medications called biologics, which target certain inflammation-causing proteins in the body. These drugs include certolizumab, & are following
• Adalimumab – Adalimumab, like infliximab, is an antibody that targets tumor necrosis factor. It has been shown to reduce the signs and symptoms of and is approved for the treatment of, moderate to severe Crohn’s disease in adults who have not responded well to conventional treatments and who have lost response to or are unable to tolerate infliximab
• Natalizumab – Natalizumab is an anti-integrin monoclonal antibody that has shown utility as induction and maintenance treatment for moderate to severe Crohn’s disease. Natalizumab may be appropriate in patients who do not respond to medications that block tumor necrosis factor-alpha, such as infliximab.
• Ustekinumab – Ustekinumab is a monoclonal antibody that suppresses cytokines IL-12 and IL-23. Originally designed to treat psoriasis, Ustekinumab was FDA approved for the treatment of Crohn’s Disease in 2016. Evidence from four quality randomized control trials suggest that Ustekinumab is effective for induction of clinical remission and clinical improvement in patients with moderate to severe Crohn’s Disease
• Infliximab – Infliximab is a mouse-human chimeric antibody that targets tumor necrosis factor-alpha (TNFα), a cytokine in the inflammatory response. It is a monoclonal antibody that inhibits the pro-inflammatory cytokine TNFα. It is administered intravenously and dosed per weight starting at 5 mg/kg and increasing according to the character of the disease.
• Aminosalicylates – 5-ASA compounds, such as mesalazine and sulfasalazine, have shown to be of very little efficacy in the treatment of Crohn’s disease, either for induction or for maintenance of remission. Current guidelines do not advise the use of 5-ASA compounds in Crohn’s disease.
• Disease-modifying agents – such as and adalimumab are used in the treatment of active moderate-to-severe Crohn’s disease that has not responded to other medications. These medications act by disrupting the inflammatory process. Their use is somewhat restricted because they are expensive.
• Small bowel resection – People with severe Crohn’s or those who develop an obstruction in the small intestine (from, for example, the accumulation of scar tissue) may need to undergo small bowel resection surgery to remove part of the intestine.
• Anti-diarrheal and fluid replacements – when the inflammation subsides, diarrhea usually becomes less of a problem. However, sometimes the patient may need something for diarrhea and abdominal pain.
• Methotrexate – is a folate anti-metabolite drug that is also used for chemotherapy. It is useful in the maintenance of remission for those no longer taking corticosteroids.
• Thalidomide – has shown efficacy in reversing endoscopic evidence of disease.
• Cannabis – may be used to treat Crohn’s disease because of its anti-inflammatory properties. Cannabis and cannabis-derived drugs may also help to heal the gut lining and may reduce the need for surgery and other medications.
• Non-steroidal anti-inflammatory drugs (NSAIDs) –  such as ibuprofen and naproxen, can cause flares of inflammatory bowel disease in approximately 25% of patients. These flares tend to occur within one week after starting regular use of the NSAID.
• Iron supplements – If you have chronic intestinal bleeding, you may develop iron deficiency anemia and need to take iron supplements.
• Vitamin B-12 shots –  Crohn’s disease can cause vitamin B-12 deficiency. Vitamin B-12 helps prevent anemia, promotes normal growth and development, and is essential for proper nerve function.
• Calcium and vitamin D supplements – Crohn’s disease and steroids used to treat it can increase your risk of osteoporosis, so you may need to take a calcium supplement with added vitamin D.
• Consider multivitamins – Because Crohn’s disease can interfere with your ability to absorb nutrients and because your diet may be limited, multivitamin and mineral supplements are often helpful. Check with your doctor before taking any vitamins or supplements.
• Helminthic therapy – In an experimental idea called helminthic therapy, moderate hookworm infections have been demonstrated to have beneficial effects on hosts suffering from diseases linked to overactive immune systems. This may be explained by the hygiene hypothesis. Hookworm therapy is currently in the trial stage at the University of Nottingham. Due to the unconventional nature of this therapy, it is not widely used.
• In contrast – acetaminophen (paracetamol) and aspirin appear to be safe. Celecoxib, a cox-2 inhibitor, also appears to be safe, at least in short-term studies of patients in remission and on medication for their Crohn’s disease.

Surgical Management

• The majority of patients diagnosed with CD will have a surgical resection within 10 years of their diagnosis [rx]. Surgical treatment is required for failed medical therapy, recurrent intestinal obstruction, malnutrition and for septic complications such as perforations and abscesses.
• It has a role in limiting other complications including complex perianal disease and internal fistulas [rx] as well as improving quality of life.
• However, the underlying pathology still persists resulting in high recurrence of disease, ranging from 28 to 45% at 5 years and 36 to 61% at 10 years [rx]. Surgical admissions account for more than half of all hospitalizations and account for almost 40% of total financial costs to patients [rx].
• Laparoscopy has been widely accepted in gastrointestinal surgery over open surgery in CD [rx]. Whilst laparoscopy offers certain advantages of smaller abdominal wounds, lower risk of a hernia and decreased rate of small bowel obstruction, there are concerns that occult segments of disease and severe strictures can be missed due to limited tactile ability [rx].
• However, a meta-analysis on perioperative complications and long-term outcomes between open surgery and laparoscopic surgery found a nonsignificant difference in rate of surgical recurrence and a decreased risk of perioperative complications in the laparoscopic group compared to the open surgery group (12% to 18%, RR = 0.71 CI = 0.58–0.86, p = 0.001) [rx]. The overall cost including hospital stay costs and costs associated with lost working days between laparoscopic-assisted bowel resection and open surgery was no different [rx].

The lifestyle of Crohn’s Disease

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