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Crohn’s Disease: It is not Just Another GI Disorder

Crohn’s disease is an inflammatory bowel disease that was first described by Dr. Burrill B. Crohn in 1932. Ulcerative colitis is another inflammatory and while the symptoms between the two are similar, it is important to make a distinction between the two.  Crohn’s Disease most commonly affects the ileum and proximal colon but can affect any portion of the GI tract, from the mouth to the colon. In contrast, ulcerative colitis affects exclusively the colon. In addition, ulcerative colitis affects the entire bowel wall thickness while Crohn’s disease affects the innermost layer and can skip areas, leaving normal intestine between affected areas.

In the US it is estimated  that there are 26-199 people out of every 100,000 who suffer from Crohn’s disease. It is observed more frequently in women, whereas ulcerative colitis is seen more in men. Inflammatory bowel disease (IBD) in general appears to affect Caucasian and Ashkenazic Jews more than other races although this difference appears to be narrowing.  Also, IBD is more prevalent on developed countries and there seems to be a north to south variation. Urban communities additionally have a higher rate of IBD than rural communities.

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Symptoms of Crohn’s disease can help classify the severity of the disease:

Mild to Moderate:

  • Frequent diarrhea
  • Abdominal pain that doesn’t affect ability to walk or eat
  • No signs of dehydration, high fever, tenderness of the abdomen, painful masses, obstruction or weight loss more than 10%

Moderate to Severe:

  • Frequent diarrhea
  • Abdominal pain or tenderness
  • Fever
  • Significant weight loss
  • Significant anemia

Very Severe:

  • Persistent symptoms despite appropriate therapy
  • High fever
  • Persistent vomiting
  • Intestinal obstruction or abscess
  • More severe weight loss

Symptoms can also occur outside the GI tract. In 5-20% of patients who are diagnosed with Crohn’s disease, joint pain may be observed. Some patients go on to develop arthritis similar to rheumatoid arthritis. Patients may also develop eye disorders, including corneal ulcerations,  inflammation of the iris, uveitis, or scleritis. Eye problems occur in up to 11% of Crohn’s patients. Approximately 10-20% of patients with Crohn’s disease will experience dermatolgic disorders. These include mouth ulcers or pyoderma gangrenosum.  Liver and gallbladder disorders are observed in 10-35% of patients. Low bone mass and osteoporosis is seen in 3-30% of patients, especially among those who have taken corticosteroids.

No one knows for sure what causes IBD.

There are two main theories regarding the etiology of IBD.  The first suggests that the mucosal immune system of the bowel wall becomes dysregulation resulting in an excessive immune response to normal gut microflora. The second theory postulates that alterations in the constitution of the gut microflora and/or derangements in the functioning of the epithelial barrier leading to pathologic reactions in the mucosal immune system.  Most subscribe to the view that there is dysfunction in the interaction between the gut microflora and the mucosal immune system.

There are many studies implicating Tumor Necrosis Factor (TNF) as playing a significant role in the dysfunction of the epithelial intestinal barrier which may possibly lead to Crohn’s.  One researcher suggests that this impairment leads to increased exposure to proinflammatory molecules. Breaks in the integrity of the epithelium allow these molecules to leak in and may be the precursor of the development of clinical disease. Interestingly, it was shown using various techniques that paracellular permeability is abnormal in 10-20% of first degree relatives of Crohn’s patients. An environmental factor is also suggested by the fact that this increased permeability was also found in 13-36% of spouses.  TNF levels have been shown to be elevated in patients with Crohn’s disease and there are now treatments targeted at reducing this using monoclonal antibodies.

Another study suggests that bacterial superagents are responsible for the initiation and/or severity of IBD, at least in some patients. Despite the fact that many have sought to locate the infective agent responsible, no one has yet found it.

There have been many genes implicated as predisposing individuals to IBD. However, the specific gene(s) is yet to be determined. One genetic location that is felt to play a role in IBD is the IBD1, located in the pericentromeric region on chromosome 16. Another study discovered a very significant association between Crohn’s disease and IL23R on chromosome 1p31. This chromosome encodes a subunit of the receptor for the proinflammatory cytokine, interleukin-23.  Additionally, the uncommon coding variant, rs11209026, c.1142G>A, p. Arg381G1n, seems to protect against the development of Crohn’s disease. We still do not know the specific genes responsible for IBD and more research is needed.

What tests can help to diagnose Crohn’s disease?

  • CBC: this is to determine if the patient has anemia. This aids in knowing the severity of the disease, an elevated WBC may indicate an infection.
  • Fecal occult blood
  • Colonsoscopy with biopsies
  • CT scan
  • Capsule endoscopy
  • Double-balloon endoscopy
  • Small bowel imaging

The use of barium swallows has largely fallen out of favor because of the radiation risk. CT scan can be especially helpful for isolating complications of Crohn’s Disease. The true gold standard of diagnosis is biopsy.

Crohn’s disease can be debilitating for patients. An important goal of treatment is to allow the patient to function as normally as possible. In children, an additional goal is to ensure adequate growth and nutrition. Over the past few years, treatment has changed with new therapies that can target specific GI tract locations as well as specific cytokines. This included the use of new biologic anti-TNF agents, which include infliximab, adalimumab, certolizumab pegol, and natalizumab. These medications have improved clinical remissions and maintenance of these remissions in moderate to severe disease. Surgery is often required in cases of obstruction, perforations, abscess formation and toxic megacolon. Surgical resection of the inflamed bowel may also be warranted if other treatments fail. Stem cell transplants have been tried experimentally and seem to offer good outcomes.

What medications are used in the treatment of Crohn’s Disease?

  • 5-Aminosalicyclic acid derivatives
  • Cortisosteroids
  • Immunosuppressive agents (eg, mercaptopurine, methotrexate, tacrolimus)
  • Monoclonal antibodies
  • Antibiotics
  • Anti-diarrheals
  • Bile acid sequestrants
  • Anticholinergic agents

Various surgical procedures may be required. These include resection of the inflamed sections of bowel, proximal loop ileostomy, drainage of any septic foci with later resection, strictureplasty, endoscopic stricture dilatation, or subtotal or total colectomy.

Various diets have been proposed to treat Crohn’s disease as well. But, there is no scientific evidence supporting the use of any specific diet plan. The best diet advice is to avoid the foods that trigger the symptoms. Additionally, the use of probiotics also remains controversial.

Patients with Crohn’s disease suffer terribly. It is not just another diarrheal disease. They remain misunderstood by the public at large. Many of them suffer symptoms or complications that interfere with their daily functioning. There remains much lack of knowledge in our understanding of Crohn’s disease and more study is clearly needed.

About the Author

Linda Girgis MD, FAAFP is a family physician practicing in South River, New Jersey. She was voted one of the top 5 healthcare bloggers in 2016. Follow her on twitter @DrLindaMD.

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