Crohn's Disease

Crohn's disease is a chronic inflammatory disease of the digestive tract and it can involve any part of it, from the mouth to the anus. It typically affects the caecum and/or the terminal ileum as well as demarcated areas of large bowel, with other areas of the bowel being relatively unaffected. It is often associated with auto-immune disorders outside the bowel, such as aphthous stomatitis and rheumatoid arthritis.

Crohn's disease should not be confused with a non-progressive and non-degenerative digestive disorder called irritable bowel syndrome (IBS), which is not an autoimmune disease. Ulcerative colitis is a sibling autoimmune disease to Crohn's but only impacts the colon while Crohn's can impact any part of the digestive tract. Furthermore, Crohn's tends to affect multiple layers of the bowel lining, which can lead to many additional and hard-to-treat complications.

Symptoms

Crohn's patients typically suffer from abdominal pain, chronic diarrhea and disrupted digestion, which may make it difficult for sufferers, particularly in the acute phase of the disease, to eat and/or digest food. The inflammation can be extremely painful and debilitating. Other common complications of Crohn's include fistulas of the colon, hemorrhoids, lipid absorption problems, and anemia. Bleeding is seen in 20% cases, against 98% cases in ulcerative colitis. Rectal bleeding may be serious and persistent, leading to anemia. Bruising of the shins, varying fever symptoms, varying levels of pain, and psychological damage is seen in many cases. Children with Crohn's disease may suffer delayed development and stunted growth.

Causes

Barrier problem and autoimmunity to the luminal flora

The efficacy of immunosuppression, as well as scanty reports of complete disease resolution after bone marrow transplant, is highly suggestive of an autoimmune pathogenesis. A definite epitope to which the autoimmunity is directed is unknown, which also hampers the search for a virus or other pathogen that could induce molecular mimicry.

Present evidence suggests that there is not a single causative antigen but that the response of the mucosal immune system is polyclonal. It is mostly directed against a multitude of bacterial, not dietary, antigens. This overreaction to the normal bacteria of the intestinal flora may be due (1) to a barrier problem of the epithelial lining of the gut or (2) to a disturbed regulation of the mucosal immune system. Multiple lines of recent evidence suggest that the deficient epithelial barrier may be due to relative lack of defensins, i.e. endogenous peptide antibiotics secreted by the small and large intestinal epithelium. This lack would then allow a slow bacterial invasion with the consequence of a secondary immune response. This hypothesis also allows us to explain the frequent finding of M. paratuberculosis in the Crohn´s mucosa discussed below. A molecular mechanism for a potential dysregulation has not yet been identified.

Since Crohn's disease is often found in families, it is likely that it has a genetic component. Studies have identified a gene named CARD15 (or NOD2) which is suspected to participate in the inflammatory process at the heart of Crohn's disease. While mutations or polymorphisms (common variations) in this gene do not directly cause the disease, they may help determine who is affected or how serious one's symptoms are. One study reported that 50% of patients with Crohn's disease carried one or more mutations in CARD15. Some mutations were associated with more severe cases or earlier age or onset. While a number of independent studies have reported the association of CARD15 with Crohn's disease, some populations like the Japanese do not have these mutations. Mutations in NOD2 have been linked to low levels of alpha defensins in Paneth cells of the small intestine. Further studies are in progress to delineate the contribution of this gene.

Both Crohn's disease and ulcerative colitis are chronic, they affect men and women approximately equally, and they are most common in northern Europe and North America. Approximately 20 percent of individuals with Crohn's disease have a blood relative with some form of IBD. The onset of Crohn disease is usually between the ages of 15 and 30 with a second smaller peak of incidence between the ages of 50 and 70. Over the past decade, several reports have noted an increase in the prevalence of Crohn disease in various geographic regions. Although there are many theories concerning the cause of Crohn's disease and ulcerative colitis, none have been proven. Since many of the symptoms of Crohn's disease and ulcerative colitis are similar, diagnosis is often difficult, time consuming, and invasive. Approximately 10-12 percent of cases are not initially classifiable and are referred to as "indeterminate colitis." Over time, about half of these patients are eventually diagnosed with CD or UC.

Treatment

Medication

Acute treatment (Steroids)

Steroids are often necessary in initial stages and during flare-ups, although long-term steroid therapy is discouraged because of its well-known side effects. Traditionally, Corticosteroids such as prednisone are used because they have the longest medical history of anti-inflammatory use. However, their side-effects are also the most severe, causing insulin resistance and frank diabetes, hypertension (high blood pressure), glaucoma, osteoporosis, severe psychological issues, and many other problems after long-term use.

Chronic treatment (Steroid-sparing)

A well-established group of drugs, especially useful in mild-to-moderate disease, are salicylates - 5-ASA derivates - 5-aminosalicylic acid compounds such as sulfasalazine (Azulfidine ®, Salazopyrin ®), mesalamine (Pentasa®, Asacol®), olsalazine, and balsalazide. Immunomodulating drugs such as azathioprine, 6-mercaptopurine and methotrexate are given mainly in moderate-to-severe cases. Research trials are being conducted on treatment with drugs in the same family as thalidomide. Infliximab (brand name Remicade®) is given in patients with therapy-resistant or fistulating Crohn's. Adalimumab (brand name Humira®) has been used in patients who show allergic reaction or diminished response to infliximab.

Surgery

Surgery (resection of parts of the bowel) is avoided, as this does not cure the disease - it can recur at any site in the digestive tract. 50% of all Crohn's patients eventually undergo one or more resections to control highly active disease. Most often, this is of the terminal ileum. In some cases of wide-spread intractable Crohn's colitis, removal of the colon and rectum (protocolectomy) is required. In these cases, the patient is left with an ileostomy.

According to the Crohn's and Colitis Foundation of America, patients who have had a resection have a 20% chance of recurrence of Crohn's after two years, increasing to approximately 50% after five years. Patients who've had a proctocolectomy with ileostomy have a recurrence rate of less than 20%. Crohn's most commonly recurs at the site of the anastomosis or ileostomy.

Dietary

Paying close attention to diet can help reduce the number and severity of flare-ups for many sufferers. Patients are encouraged to follow a nutritious diet and limit any foods that seem to worsen symptoms. Individual reactions vary. Some foods commonly avoided by Crohn's patients are:

• Dairy foods. Some people are lactose intolerant (unable to digest the sugar lactose, found in milk products). Taking lactase tablets or specially prepared dairy products may help. Note: Many lactose-intolerant patients are still able to eat yogurt with active cultures, which may even be helpful
• Foods high in fiber, but because a high-fiber diet has other benefits, these foods might be avoided only during flare-ups.
• Foods associated with inflammation (alcohol, hot spices, and caffeine).
• Saturated fats, found in meat and dairy products. However some fats such as in fish oil may actually be helpful.
• Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
• Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
• Gas-producing foods such as cabbage family vegetables (broccoli, cabbage, cauliflower and brussels sprouts), dried peas and lentils, onions and chives, peppers and carbonated drinks
• Foods that may irritate the intestine (particularly the cabbage family vegetables).
• Simple sugars,
• Dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
• Sorbitol (an artificial sweetener)

And some foods may also be beneficial:

• Fluids to keep the body hydrated and prevent constipation
• Fruits may be protective
• A high protein diet with lean meats

Other advice:

• Trying small frequent meals may also help.
• There have also been some suggestions that prebiotics such as psyllium may help in the healing process. Furthermore, probiotics (live culture) may also be helpful in aiding recovery of the intestines.