Inflammatory Bowel Diseases
 
Under this name we group several diseases that share some similarities but also have very distinctive features.  The main two diseases in this group are Crohn’s disease and ulcerative colitis.  In addition to these two there are several other inflammatory processes of the colon called colitides. This includes: collagenous and lymphocytic colitis, colitis cystica profunda, diversion colitis and segmental colitis associated to diverticulitis.   The key feature of inflammatory bowel diseases is that there is an abnormal interaction of the immune system of the gut and intestinal bacteria. 
 
While these diseases have been called autoimmune diseases they really don’t meet the postulates of an autoimmune disease such as rheumatic fever.  There is no specific antigen or specific target like in rheumatic fever or lupus. 
 
Therefore, the underlying problem is thought to be an improper regulation of the gut immune system overreacting to intestinal bacteria.  Inflammatory bowel disease can be induced in animals but if animals are kept in a sterile environment since birth so that the gut never develops a flora the inciting stimuli for inflammatory bowel disease do not work.
 
It is known that inflammatory bowel diseases are more prevalent in some ethnic groups, such Ashkenazi Jews, and that there is a familial tendency to develop these diseases.  Over the past few years several gene abnormalities have been implicated in the development of inflammatory bowel disease. However, any of these gene abnormalities is found in only 30% to 40% of patients; therefore, there must be multiple ways of contracting these diseases. 
 
Contrary to other illnesses such as cancer where there are records of cases going back many centuries the first cases of inflammatory bowel diseases were described in the early 1900s and in industrialized countries. 
 
There have been multiple epidemiological studies linking inflammatory bowel disease to refined sugar, refrigerated food (the cold chain theory), food additives, toothpaste, microorganisms such as the mycobacteria avium paratuberculosis and the measles virus, and  the loss of helminthes (parasites) in the bowel.  Clearly something has come along with industrialization that has render the bowel to overreact to some type of intestinal bacteria.
 
Although Crohn’s disease and ulcerative colitis are the two most distinctive forms of inflammatory bowel disease there are multiple subtypes within each of these two diseases.  It is very possible that in the near future these two diseases will branch out into many others that will be characterized by genetic markers. 
 
Crohn’s disease:
 
The main distinctive feature of Crohn’s disease is that the inflammation in the bowel produces a typical lesion under the microscope called a noncaseating granuloma.  This is a granuloma is a nodule consisting of inflammatory and immune cells as well as extracellular matrix. 
 
Granulomas form when the immune system attempts to fend off and isolate an antigen. An important distinction of granulomas is whether they are caseating or not. Caseation (literally: turning to cheese) is a form of necrosis at the centre of a granuloma and is a feature of the granulomas of tuberculosis.  Crohn’s disease produces the noncaseating granulomas and these can be found anywhere in the gastrointestinal tract from the mouth to the anus.
 
Along with this inflammatory process of the bowel wall patients experience pain, symptoms of blockage, bleeding, abscesses from perforations of the intestine abnormal communications between hollow viscera and the skin or internally among themselves. In very rare cases patients with Crohn’s disease develop spontaneous, free perforations with peritonitis.
 
Traditionally, the preferred form of treatment for Crohn’s disease has been pharmacologic including corticosteroids (prednisone), aminosalicylic acid derivatives, and immune suppressive drugs: methotrexate, azathioprine and 6-mercaptopurine. More recently a new line of drugs has been introduced that are targeted against some mediators of inflammation. The mediator is Tumor Necrosis Factor (TNF), and the drugs are antibodies against TNF produced from either human or mice proteins. 
 
Surgery has been reserved for cases where the medications are no longer working or life threatening complications have developed that can only be corrected with surgery.  This approach of escalating drug therapy first and reserving surgery as a last resort is called the “step up approach”.  Several “markers” are been studies to select a specific therapy  for an individual patient.  This is done because it is recognized that in some patients the step up approach does not work and just delays the inevitable exposing the patient to unnecessary risks.
 
For instance, immune suppression makes surgery more risky in terms of infections and breakdown of wound from poor healing. If we could predict that a patient will need surgery regardless of how many drugs are tried it would make more sense to perform surgery early on and spare the patient from the delay and the risks associated with drug therapy. This approach is called “top down” and is gaining more acceptance as physicians are becoming more familiar using markers (blood tests) to grade bowel inflammation.
 
Historically, surgery for Crohn’s disease has been associated with several adverse outcomes. First, patients with Crohn’s disease seemed to have more complications than patients having similar surgeries for conditions other than Crohn’s disease. Second, many patients who undergo surgery after many years of Crohn’s disease begin having more frequent relapses after surgery as if surgery triggers more inflammation.  Lastly, surgery leads to more surgery and progressive loss of length of bowel until the patient becomes dependent on parenteral nutrition for survival. 
 
While these adverse outcomes are possible there are usually preventable.  Complications after surgery have been linked to two factors: long term use of corticosteroids and presence of infection in the abdomen prior to surgery.  This is way prednisone is no longer prescribed for maintenance in Crohn’s disease.  It is only used in short courses when everything else has failed.  Intrabdominal infection can be cleared before surgery by placement of drainage catheters in radiology before surgery. 
 
The issue of recurrence and need for reoperations goes back to the days when surgery was thought to be curative of Crohn’s disease. We now recognize that Crohn’s can be latent anywhere in the gut aside from the segments grossly affected on which surgery is done. Therefore, all patients continue to receive medication after surgery even if the surgeon removes all visible disease.  With the introduction of these measures surgery for Crohn’s disease is as safe and effective as for other diseases: ulcerative colitis or diverticulitis.
 
Ulcerative colitis:
 
The distinctive feature of ulcerative colitis is that it only affects the colon and not the small bowel.  Also, it begins from the rectum up without skipping any areas (a pretty common feature of Crohn’s disease).  Finally, ulcerative colitis affect the inner layer of the colon or mucosa where it produces inflammation, it is not unusual to look at the bowel from its outside during surgery and think that is quite healthy because the outer layer is not affected.  Crohn’s disease is called transmural because it progresses through all layers of the intestinal wall.
 
The chief symptom of ulcerative colitis is bloody diarrhea. Pain, obstruction and perforation are extremely rare in ulcerative colitis. The inflammation of the rectum also produces a constant urge to defecate not relieved by bowel movements, and incontinence. In severe case the bowel becomes distended and the body can start absorbing toxic substances contained in the colon, this entity is called toxic megacolon and requires immediate surgical intervention.
 
Some patients go on to resolve their symptoms by taking medication.  In spite of no longer having symptoms all patients with ulcerative colitis need to have colonoscopies.  The likelihood of colon cancer is significantly increased when a patient has had ulcerative colitis and this likelihood is greater in patients who have had ulcerative colitis for more than 20 years and have involvement of the entire colon (pancolitis or universal colitis).   Therefore, multiple biopsies are obtained with each colonoscopy and pathologists study them for changes in cellular architecture of the mucosa. 
 
From either a normal architecture or a background of chronic inflammation the mucosa may change to dysplasia which is a precancerous condition.  Patients with dysplasia are referred for surgery even if they have no signs or symptoms of inflammation.
 
The majority of patients referred for surgery are neither suffering a toxic megacolon or dysplasia.  Some have coped with the disease for many years with multiple medications and they begin having reactions or side effects to the medications. Others have chronic anemia and fatigue from persistent blood loss.  Another group of patients develop extraintestinal manifestations of ulcerative colitis in the form of arthritis, sacroilietis, ankylosing spondylitis, erythema nodosum and slerosing cholangitis.  With the exception of sclerosing cholangitis all others tend to regress when the colon is removed.
 
Undeterminate Colitis:
 
When considering surgery, the distinction between Crohn’s disease and ulcerative colitis is very important.  The best surgical option for ulcerative colitis is the restorative proctocolectomy which means removal of the colon and rectum with the creation of an internal pouch made out of the end of the small intestine (ileum) cionceted to the anus: ileoanal pullthrough or ileal pouch anal anastomosis.  
 
While this operation works very well in patients with ulcerative colitis (and also in those with familial adenomatous polyposis)  it usually fails in patients with Crohn’s disease.  Unfortunately, there is a group of patients with features of ulcerative colitis but also some features of Crohn’s disease and nothing definitive to indicate which one it really is.  Most of these patients are ttreated as if they have ulcerative colitis and do well with a pouch operation. A small number of them may lose to the pouch later on to Crohn’s disease.

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