Crohn’s disease

Crohn’s disease is a type of inflammatory bowel disease (IBD). As the name implies, IBDs are characterised by chronic intestinal inflammation (swelling due to cellular processes). The other major IBD is ulcerative colitis.

Introduction

In Crohn’s disease the characteristic feature is inflammation of the bowel mucosa or lining. It most commonly affects the lower small intestine (ileum) and the large intestine (colon), but may involve any part of the digestive tract from the mouth to the anus. The inflammation extends through the entire thickness of the intestine. Patients of Crohn’s disease experience abdominal pain, diarrhea and a range of other symptoms including fever and weight loss.

The disease occurs about equally in men and women and usually appears for the first time in people of less than 30 years old mostly in those aged 14-24 years. A smaller proportion of people between the ages of 50 and 70 years also develop Crohn’s disease but the disease can occur in people of any age.

Causes

The cause of Crohn’s disease is unknown, although people with a family history of IBD are at an increased risk of developing the disease. About 20% of people with Crohn’s disease seem to have a blood relative (especially a sibling and sometimes a parent or child) with some form of IBD. Cigarette smoking has also been shown to contribute to the development or exacerbation of the disease.

The inflammation in Crohn’s disease has in the past been thought to be related due to autoimmunity. The immune system is a defence system of the body composed of cells and proteins that normally protect the body from harmful infections and foreign bodies. When there is introduction of a foreign body or microbe or pathogen the immune system recognises them and mounts a retaliatory response through mobilization of specialized cells which attack the alien cells or proteins and try to destroy and expel them. During this stage there is inflammation in the related cells and tissues. The immune system is usually able to differentiate between food, beneficial bacteria and other normal bowel components and pathogens, microbes, foreign bodies etc. In people with Crohn’s disease however, the immune system seems to be overreacting to substances and bacteria in the intestine. As in a normal immune response white blood cells invade the intestinal lining and produce inflammatory toxins causing chronic tissue swelling, injury and ulceration. The precise cause of this abnormal immune response is unknown although the existence of a specific infectious agent has not been disproved. Apart from genetic predisposition certain chromosomal markers have been found in the DNA of patients with Crohn’s disease.

Infection research

For years, research has been undergoing to find an infectious cause for Crohn’s disease. A growing body of evidence suggests that a bacterium called Mycobacterium avium subspecies paratuberculosis (MAP) may infect a genetically susceptible subgroup of the population resulting in Crohn’s disease. Researchers here at the Centre for Digestive Diseases have been instrumental in revealing this possibility and remain at the frontline of international research in this area.

Symptoms

The most common symptoms associated with Crohn’s disease include abdominal pain, often in the right lower area, and diarrhea. Rectal bleeding, loss of appetite, fever and weight-loss may also occur. Bleeding may be long-term and cause anaemia. Being a chronic disease, patients with Crohn’s disease experience bouts of Crohn’s disease intermixed with periods of remission. Other non-specific symptoms like fatigue, joint pain and skin problems may also be experienced. Some bouts may be severe and some may be mild and it also differs between different individuals. Children with Crohn’s disease may suffer delayed development and stunted growth.

Some bouts may be severe and some may be mild and it also differs between different individuals. Children with Crohn’s disease may suffer delayed development and stunted growth.

People with Crohn’s disease may feel well and be free of symptoms for substantial periods of time when their disease is not active. Despite the need to take medication for long periods of time and occasional hospitalizations, most people with Crohn’s disease are able to hold jobs, raise families, and function successfully at home and in society.

Complications

Complications in Crohn’s disease are usually due to the chronic inflammation. These usually manifest only in severe disease. Frequent inflammation of the intestinal walls leads to stiffening and narrowing of the bowel lumen causing intestinal obstruction, further resulting in constipation and poor absorption of nutrients leading to malnutrition. Tears may develop in the lining of the anus resulting in anal fissures. In some cases, fistulas can develop. This is a connecting tunnel between two or more sections of the bowel or between bowel and other structures in the vicinity like bladder, vagina or the skin near the anus. The usual place for a fistula is near the anus known as perianal fistula.

Nutritional complications are common in Crohn’s disease, including deficiencies of certain proteins, calories and vitamins. Other complications associated with Crohn’s disease include arthritis, skin problems, inflammation of the eyes and mouth, kidney or gall stones and liver disease. These problems often resolve with appropriate management of the inflammatory process, but sometimes require separate treatment.

Diagnosis

Clinical diagnosis of Crohn’s disease can be challenging due to the similarity of its symptoms with other GI disorders such as ulcerative colitis and irritable bowel syndrome. Blood tests and laboratory tests can indicate anaemia, inflammation and malabsorption. After getting a preliminary diagnosis from the indicative medical history the gastroenterologist may order non-invasive investigations such as plain x-rays, barium x-rays, computed tomography (CT) scans and magnetic resonance imaging (MRI). Barium x-rays used to be the only modality a few decades back. The subject is made to swallow a chalky barium meal and x-rays are taken.

For a definitive diagnosis a colonoscopy is recommended and biopsies (tissue samples) of the polyp may be taken to confirm histopathologically. Histopathological examination involves examining a slice of the tissue sample after appropriate staining through a microscope for cellular level changes that is confirmatory of Crohn’s disease. Samples of luminal fluid may be taken for bacteriological examination and culture to look for secondary infection which may be causing the inflammation or aggravating it.

Treatment

Treatment for Crohn’s disease depends on the location and severity of disease, complications, and response to previous treatment. The goals of current treatment strategies are to control inflammation, relieve symptoms and correct nutritional deficiencies. At this time, treatment can help control the disease, but there is no cure. People with Crohn’s disease may need medical care for a long time with regular doctor visits to monitor the condition.

Anti-inflammatory agents

The class of drugs known as aminosalicylates (5-ASA) are used to treat mild to moderate inflammation in Crohn’s disease. By controlling inflammation, these drugs are generally effective at inducing and maintaining remission of disease. They include sulphasalazine, mesalazine, olsalazine and balsalazide. Possible side effects of 5-ASA preparations include nausea, vomiting, heartburn, diarrhoea and headache.

This type of drug has also been shown to have activity against MAP which is found to be present in a good proportion of patients with Crohn’s disease and is currently under further investigation. These drugs are usually combined with other drugs.

Omega-3 fatty acids are also anti-inflammatory agents which can be useful in therapy of IBD.

Immunosuppressive agents

Some patients take corticosteroids to control inflammation. These drugs non-specifically suppress the immune system and are used to treat moderate to severe Crohn’s disease. They treat the acute stages of disease by dramatically reducing fever and diarrhoea, relieving abdominal pain and tenderness, and improving appetite and general sense of well-being. They include prednisone in oral and rectal forms, I.V. hydrocortisone and budesonide, oral or enema.

Long-term corticosteroid therapy can induce serious side effects, most notably skin and bone changes and greater susceptibility to infection, and should be avoided if possible. Short term steroids can be very useful but long term steroids are now generally avoided.

Other immunosuppressive agents work by specifically blocking the immune reaction that contributes to the inflammation in Crohn’s disease. They work by specifically blocking immune reaction that contributes to inflammatory inflammation of Crohn’s disease and most of them have anti-MAP activity.

Azathioprine and 6‑mercaptopurine improve overall clinical status, decrease the need for corticosteroids and help to maintain remission. Their action may not take effect for 2-6 months however and their use must be closely monitored for side -effects such as nausea, vomiting, diarrhoea, allergy, decreased white blood cell count and pancreatitis.

Other immunomodifiers such as methotrexate, cyclosporine and infliximab are sometimes used to treat severe Crohn’s disease that is non-responsive to other forms of treatment.

Antibiotic agents

Koch’s postulates have now been fulfilled proving that in a subset of patients the mycobacterium MAP is involved in the development and persistence of inflammation in Crohn’s disease.

Antimycobacterial agents specifically targeting this causative pathogen have shown success in inducing remission in severe disease and may even prove to be able to cure the disease in a subset of patients.

The Centre for Digestive Diseases is a leader in this area of research and recently an Australia-wide trial has been completed against MAP, the results of which have shown that the highest reported remission can be achieved with anti-MAP therapy. However due to some limitations in the trial the long term maintenance part of the trial cannot be currently accepted as having any clinical significance.

Certain clinical trials have also shown that broad-spectrum antibiotics such as metronidazole and ciprofloxacin also have benefit in the treatment of Crohn’s disease but need to be taken long term as they have known anti-MAP activity.

Surgery

Patients with Crohn’s disease may eventually require surgery for its complications. Surgery is used to solve specific problems such as stricture, obstruction, fistulae or overwhelming disease with non-response. Surgery does not cure the disease, just relieves the major complications. The patient makes this decision after close consideration of information given by doctors, nurses, other patients and support groups.

Nutritional supplementation

Nutritional supplements may be recommended, especially in children with impeded growth and development. Special high calorie liquid formulas are sometimes used for this purpose. A small number of patients with absorption problems or malnutrition may require feeding by vein.

Further research

Many new drug modalities are being researched to provide longer periods of remission or to cure Crohn’s disease. The Centre for Digestive Diseases has in the past contributed to some of the key research areas in Crohn’s disease and is actively involved in research on this area. For further information please look into our research section or get in touch with us.

Further reading

http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/small_large_intestine/crohns_disease.pdf

http://www.aafp.org/afp/2011/1215/p1365.html