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Inflammatory Bowel Disease.

Dr.Barin Bose MS, FACRSI.
Jabalpur Hospital and Research Centre
Jabalpur (M.P.)

It is a nonspecific inflammatory disease of unknown aetiology, affecting the bowel. A number of other conditions which are associated with inflammation of the bowel are -

¢ Bacterial Colitis.
¢ Parasitic Colitis.
¢ Radiation Colitis.
¢ Ischemic Colitis.

Until the causes of Ulcerative Colitis and Crohn's disease are identified, the term inflammatory bowel disease serves a useful purpose to distinguish these conditions from other bowel disorders. It is most commonly seen in the age group of 15 to 25 years, however a second peak in the incidence of IBD is seen at 60 to 70 years age. About 15 % of patients suffering from IBD have a close relative who also have IBD.

Ulcerative Colitis

It is a nonspecific inflammatory disease of unknown aetiology affecting the large bowel. It is seen in both sexes and at any age but mostly affecting the second to fourth decades of life. Auto immunity, allergy to milk protein and genetic factors mostly predisposes to aetiological factors.

Clinical Features - The severity vares from mild inflammation of mucosa to fulminating ulceration of colonic mucosa. The disease shows exacerbation and remission of varying intervals. It affects the variable part of large bowel, as proctitis, proctosigmoiditis, left sided colitis and pancolitis. The disease does not involve the small intestine but at times reactionary inflammatory changes are seen in terminal ileum which is called as back-wash ilitis. In mild case it may present with increased frequency of stools. In severe cases massive diarrhoea, bleeding PR, tenesmus, abdominal cramps and fever are present. The predominant symptoms are bloody stools and diarrhoea. The severity of bleeding is in proportion to the stage of the disease, and nocturnal diarrhoea is frequent. Signs are minimal and nonspecific in mild cases. In severe cases abdominal tenderness, abdominal distension, fever, tachycardia, raised TLC are present. Bad prognosis is indicated by (1) A sudden and severe initial attack (2) Disease involving the whole of colon (3) Increasing age especially after 60 years. Prognosis is good if disease involve the left half of colon.

Pathology- Microscopically acute and chronic inflammatory response is seen in the mucosa and submucosa with ulceration and regeneration. Multiple crypt abscesses are seen. During remission phase acute response is absent. The mucosa is atrophic, reduced goblet cells, crypts are distorted, submucosa thickened. Other coats are not involved and the inflammatory lesions are limited to mucosa and submucosa. The mucosa become swollen, friable, which leads to ulceration, which involves the full thickness of mucosa. In early stage small ulcers are present on mucosa,which later coalesces to give extensive denudation. Secondary infection occurs on these denuded areas. In chronic stage the disease starts in rectum leading to proctitis, later it extends proximally to involve the sigmoid colon, descending colon - proctosigmoiditis - left half colitis. In severe cases pancolitis results. The episode of ulceration leaves behind island of mucosa which regenerates in chronic case to form polyp like structures which are called pseudopolyps. In severe fulminating cases the wall of colon becomes thinned out, specially seen in transverse colon, which become dilated leading to toxic megacolon, at this stage the colon may perforates, resulting in perforation peritonitis.

Malignant changes - Frequency of malignant change in ulcerative colitis is high. The high risk factors includes (1) Childhood onset. (2) Pancolitis. (3) Duration of disease is more than 10 years.
Investigations - (1) Proctoscopy - Loss of normal vascular pattern of mucosa due to mucosal edema. Mucosa shows edematous, inflamed, granularity and friability. Ulceration and bleeding points.Fine granularity is seen in acute cases and coarse granularity is seen in chronic disease. Biopsy in acute stage shows nonspecific inflammatory changes and is not diagnostic.
(2) Colonoscopy and Biopsy -Is done to -
(1) Establish the extent of disease.
(2) Distinwish between Ulcerative Colitis and Crohn's Disease.
(3) Monitor the response of treatment.
(4)Multiple biopsies are taken to know the dysplastic changes in diseases which are more than 10 years duration.
(3) Barium Enema - Shows -
(1) Loss of haustrations especially in distal colon.
(2) Mucosal changes due to granularity.
(3) Pseudopolyps.
(4) In chronic cases a narrow and contracted colon.
(5) In Chronic cases colonic stricture may be seen. (Colonic stricture in Ulcerative colitis should be taken as malignancy unless proved otherwise.)
If the disease is more than 10 years old annual colonoscopy is to be done even if the disease is quiescent to rule out malignant changes.
Extraintestinal Manifestation -(1) Arthritis (2) Skin lesions - Pyoderma gangrenosa.
(3) Clubbing of fingers. (4) Iritis. (5) Liver disease - Sclerosing Cholangitis. (6) Bile duct malignancy.


Medical Treatment

(1) Diet and Nutrition : Patients with mild attack of IBD are able to take food orally. Fibres are restricted during active symptoms. Patient with Crohn's Disease have terminal ileal involvement and steatorrhoea. These patient with Crohn's disease require fat soluble vitamin supplementation. Parenteral B12 supplementation. Iron replacement. In severe IBD patient are nil by mouth and require TPN.
(2) Drugs : Sulphasalazine and aminosalicylates are the most commonly used drugs in IBD It has been shown to be effective in the treatment of active as well as remitted case of ulcerative colitis and Crohn's disease, when colon is involved.The drug sulfasalazine consists of two drugs, a Supfapyridine and a 5 Aminosalicylic acid (5 ASA) which are linked by azobond. Intestinal bacteria breaks the azobond and release the 2 components. The sulfapyridine is systemically absorbed and is excreted in the urine. The active component 5 ASA is not absorbed and remains in the gut lumen in contact with the mucosa and is excreated with the stools.. Side effect - Abdominal discomfort , it is due to the effect of salicylates on the upper GI tract. This problem can be minimized by giving Supfasalazine with meals. Sulfasalazine competes with folates for absorption so patients become folate deficient. Other side effect are skin eruption, bone marrow depression is due to sulfapyridine part. Dosage : The initial daily dose is low (1 Gm) to minimize GI side effects . A therapeutic dose of 3 to 4 Gms per is appropriate. CBC and liver chemistry is done every 3 months initially then every 6 months in the long term treatment. Maintenance treatment of 2 to 3 Gms per day in divided dose has been shown to reduce the frequency of exacerbations of ulcerative colitis.
Other 5 ASA Preparations- The side effect of sulfasalazine is due to the Sulfapyridine part of the drug. So the interest is to develop a drug which has the salicylate part but not the sulfapyridine part. Several oral 5ASA preparations are available, Olsalazine which consists of two 5ASA molecules joined by an azobond and which require bacterial degradation in the colon to release the 2 molicules of 5ASA. Asacol and Pentasa are controlled release tablets of 5ASA . Balsalazine is a newer 5ASA preparation which is effective in the treatmrnt of IBD involving left sided colon. Topical 5ASA preparations are Mesacol enema and Mesacol suppositories. 5ASA preparations are also recommended in patients with Crohn's disease to prevent post operative recurrence.
Corticosteroids- Corticosteroids has been used in the treatment of severe ulcerative colitis and Crohn's disease to reduce remission. IV Hydrocortisone 100 to 200 Mgs 6 hourly is used. Or Methylprednisolone in the dose of 10 to 20 Mgs IV 6 hourly are usually used in such patients. When patients can take oral medicines, prednisolone tablets in a dose of 40 to 60 Mgs per day usually given for 3 to 4 weeks. When symptoms improves the drug is tapered off in several months. Steroids are not recommended for maintenance therapy of Ulcerative colitis and Crohn's disease because steroids do not prevent relapse of UC and Crohn's disease and they have major side effects. Many patient become Steroid dependent when recurrence of symptoms occur when dose of steroids are reduced. In such cases one strategy is to use immunomodulators such as Azathioprim, 6 Mercaptopurine, Methotrixate, Cyclosporin, in steroid dependent patients to help tapper the dose of steroids, second option is Surgery. Corticosteroid enemas are also available for the treatment of proctitis and distal colitis.
Antibiotics - Most patients with mild to moderate IBD are successfully treated by Sulfasalazine or 5ASA and occasionally may require systemic or topical steroids therapy to treat disease relapse. However 20 to 30 % of patients with Ulcerative colitis and 30% of patients with Crohn's disease require additional therapy for refractory disease. Bacteria are known to play an important role in the pathogenesis of Crohn's disease and Ulcerative colitis. In Crohn's disease antibiotics are used to treat perianal abscesses and fistula, microperforation, localized peritonitis, bacterial overgrowth in chronic stricture. Antibiotics should be considered in patients not responding to 5ASA preparations prior to initiating steroid therapy. (a) Metronidazole - Has been shown to be effective in patients with Crohn's disease of the colon of combined small bowel and large bowel disease, and in perirectal and fistulizing Crohn's, some patient with Ulcerative colitis also responds to Metronidazole.
(b) Ciprofloxacine- Useful in patients with colonic Crohn's and in perirectal and fistilising Crohn. (c) Combination of Metronidazole and Ciprofloxacine.
Indications of Immunomodulator Drugs.

Crohn's disease. Ulcerative Colitis.

(1) Refractory Crohn's. Refractory Ulcerative colitis.
(2) Steroid Dependent. Steroid Dependent.
(3) Remission &maintenance of Crohn's Remission &maintenance of UC.
(4) Fistulizing Crohn's.
(5)Prevention of Post operative recurrence.

They are -(1) Azathioprim (2) 6 Merkaptopurine. (3) Cyclosporin. (4) Methotrixate.
(5) Infliximab - It is an antibody against Human Tumour Necrosis Factor -2. which play an important role in pathogenesis of Crohn's disease. Infliximab is effective in the treatment of moderate to severe active Crohn's disease and fistulising Crohn's. It may also be beneficial in severe active UC. Further studies are underway to see the long term use of Infliximab in IBD. It is advisable to continue the use of 5ASA, antibiotics, steroids and immunomodulator drugs, during and after the infusion of Infliximab.
Nicotine -In enema form has been shown beneficial in Ulcerative colitis.
Antidiarrhoeal Drugs - If diarrhoea does not improve with the above mentioned medical therapy the antidiarrhoeal drugs can be used. Codine is most effective. Imodium and Lomotil is used in mild to moderate IBD. Insevere IBD they should not be used as they tend to precipitate toxic megacolon.
Bile acid binding resins - Because of patients with Crohn's disease have involvement of terminal ileum which results in bile acid malabsorption, diarrhoea, steatorrhoea. Treatment with bile acid binding resins are indicated such as Cholestyramine.

Surgical Management -

Indication for Surgery - Risk of colectomy is 20% in overall ranging from 5% in those patients with only proctitis to 50 % in those patients with severe attack of pancolitis.
(1) Severe fulminating disease failing to respond to medical therapy for 7 days.
(2) Chronic disease with anemia.
(3) Steroid dependent disease - Here the disease is not severe but remission cannot be maintained without substantial dose of steroids.
(5) Severe haemorrhage, stenosis, obstruction, perforation.
(6) Extraintestinal manifestations.
Operations - (1) Total abdominal colectomy with end ileostomy , is done in emergency situation as a first aid procedure. The restorative surgery is done at a later date ;when the patient is no longer on steroid and in optimal nutritional condition -Ileorectal or ileoanal anastomosis.
(2) Proctocolectomy with ileostomy.
(3) Restorative protocolectomy with an ileoanal pouch anastomosis. J Pouch, S Pouch,
W Pouch.
(4) Colectomy with ileorectal anastomosis when the rectum is minimally involved.

Toxic Megacolon and severe IBD - Toxic megacolon ia a condition in which the colon becomes atonic and dilated because of transmural inflammation. It is mostly associated with severe ulcerative colitis,but it may be associated with any severe inflammatory condition of the bowel.
- Crohn's disease.
- Bacterial colitis.
- Parasitic colitis.
- Pseudomembranous colitis.
- Ischemic colitis.
- Radiation colitis.
Some patient with severe ulcerative colitis do not have toxic megacolon but they require intensive treatment, because at any time toxic megacolon can be precipitated. Patient with toxic megacolon are seriously ill. They have fever, techycardia, raised TLC,bloody diarrhoea and sepsis.
Pathogenesis - In most instances of colitis inflammatory process is confined to the mucosa and submucosa. Toxic megacolon develops as a result of the extension of the inflammatory process to the muscularis mucosa and serosa , leading to peritonitis and some times perforation. Several factors predisposes to the development of toxic megacolon -
(1) Reduction in the medication of IBD.
(2) Hypokalemia causing paralytic ileus.
(3) Narcotics.
(4) Anticholenergic drugs.
(5) Drugs which dimnish bowel movements.
(6) Cessation of smoaking in patient with Ulcerative Colitis.
Bowel stasis facilitates extension of inflammatory process. The sign and symptoms are - At initial stages there is worsening of diarrhoea (more than 6 stools per day), fever , tachycardia , abdominal tenderness, abdominal distension. As the disease progress the stool frequency diminish and the colon become atonic and dilated. Physical examination shows -
- Patient appear severely ill.
- Sign of systemic toxicity. Fever, tachycardia, change in mental status.
- Abdomen is diffusely tender.
- Abdomen is distended.
- Bowel sounds are absent .
- Sign of peritonitis.
- P/R shows bloody stools.
Severe case of ulcerative colitis are regarded as medical emergency and should be treated in hospital. Patient should be examined twice a day for signs of peritonitis. Abdominal girth is measured . Scout film abdomen is done daily to (a) see the diameter of transverse colon, a diameter more than 6 Cms are regarded as abnormal. (b) Perforation is common in toxic megacolon thus upright or lateral decubitus films should be taken to rule out free gas.
Ba enema and Colonoscopy is contraindicated.
Sigmoidoscopy - Limited sigmoidoscopy by an experienced endoscopist is safe and indicated. The examination should be limited to rectum and distal sigmoid. The severity of mucosal injury is assessed. To know the other causes of severe colitis - Crohn's disease,
Ischaemic colitis, pseudomembranous colitis, parasitic colitis.
Management of Toxic Megacolon - (1) General Management -
- Nil by mouth.
- IV Fluids.
- RT aspiration.
- Opiates and anticholenergics should be stopped.
- Correct electrolyte imbalance.
- Correct anemia by blood transfusion.
(2) Antibiotics - Should be treated with broad spectrum antibiotics, giving a good anarobic coverage.
(3) Corticosteroids - Hydrocortisone given IV in the dose of 100 to 200 Mgs 6 hourly.
(4) Cyclosporin and Azathioprim or 6 Merkeptopurine are started.
(5) Surgery - Patients with severe Ulcerative Colitis or toxic megacolon should be treated by a surgeon early in the course of the disease. The indications of surgery are -
(1) Perforation.
(2) Unremitted colonic haemorrhage.
(3) Failure of the clinical status to improve even after intensive treatment with IV Steroid in combination with Cyclosporin.If the patient does not improve within 7 days of this regimen
should be subjected to surgery. Surgery is subtotal colectomy with ileostomy, is considered the conservative procedure of choice in patients with systemic toxicity.
But in patients without systemic toxicity - Total proctocolectomy with ileoanal pouch anastomosis is possible.

Crohn's Disease

- It was first reported by Crohns in 1932. It can affect any part of gastrointestinal tract, from mouth to anal margin.but ileocoecal involvement is the most common presentation. It is slightly more common in females than in males. It is seen in young patients of the age group of 25 to 40 years. But another peak of incidence is seen around the age group of 17 years. Although the Crohn's disease has some features suggestive of chronic infection but no definite causative organisms has been found till now. It differs from the Ulcerative colitis by its segmental involvement and it can affect any part of the gut.
Aetiology - (1) Similarities between Crohn's disease and tuberculosis has focused attention on mycobacterium. (2) Penetration of bowel mucosa by E.Coli was thought to set the inflammatory process. (3)Hereditary seems to play a strong role. Ulcerative colitis can affect the relatives of patients with Crohn's disease but not vise versa. About 10% of the patient with Crohn's disease have a first degree relative suffering with the disease. (4) Focal ischaemia has been postulated as the causative factor, possibly originating from vasculitis arising from immunological process. (5) Smoking increase the risk by 3 folds. (6) Cell mediated immune function is defective in patients with Crohn's disease, but it is not known that it is due to the consequence of the disease or it is the effect of malnutrition and medical treatment. Crohn's disease can predispose to cancer although the incidence of malignant change is not so high as in ulcerative colitis.
Pathology - Ileal disease is most common, accounting for 60% of the cases, 30% of the cases are limited to large bowel.. Anal lesions are common, but Crohn's disease of the mouth, oesophagus, stomach and duodenum are uncommon. Resected specimen shows fibrotic thickening of small bowel wall with narrowed lumen. The bowel proximal to the stricture is dilated. The mucosa shows linear or snake like deep musosal ulcers. Oedema of the mucosa between the ulcers give a cobble stone appearance. There is transmural extension of the inflammation giving rise to adhesion, mesenteric abscesses, fistula, into the adjacent organs. Serosa is opaque and mesentery is thickened with enlarged mesenteric lymph nodes. Similar lesions may be present proximally but the condition is discontinuous with the other inflamed area being separated with normal intestine. These are called as skip lesion. Microscopically - there are focal areas of chronic inflammation involving all the layers of the intestinal wall. There are noncaseating giant cell granulomas most commonly seen in the lesions of anorectal disease. The earliest mucosal lesions are the aphthous ulcers. Recent studies have shown multifocal arterial occlusion in muscularis propia.
Clinical Features -Presentation depend on the area of involvement. The disease has an insidious onset of pain in abdomen , anemia, hypoprotenemia. Acute Crohn's disease occurs in 5% of cases. Sign and symptoms resembles that of Acute Appendicitis. But there is diarrhoea preceding the attack. Rarely there is perforation of small intestine resulting in local or deffused peritonitis. Acute colitis with or without toxic megacolon can occur in Crohn's disease but it is less common than in ulcerative colitis. In chronic Crohn's disease there is often history of mild diarrhoea which is accompanied by intestinal colic since many months. Patient complains of pain in right iliac fossa, there may be tender mass palpable. Intermittent fever, anemia, hypoproteinemia, weight loss are common. Perianal abscess and fissure may be the first presentating feature in Crohn's disease. The cause is infected anal crypts due to diarrhoea. As the disease become chronic fistulae develops due to Crohn's disease itself.(1) Entero-enteric Fistula.(2) Entero-colic Fistula (3) Entero-vesical Fistula which may cause recurrent urinary tract infection and pneumaturia.(4) Entero-cutaneous Fistula is rare but may develop following surgery.
Investigations - (1) Sigmoidoscopic Examination - It is normal but ulceration in anal canal may be seen. (2) Colonoscopy - Rectal mucosa is normal in patients who have Crohn's disease without rectal involvement. Rectal Crohns shows patchy involvement. The mucosal edema,deep leniar ulcers and fibrosis are the features of chronic disease. A rare variety with involvement of colon and rectum in continuity with granular and friable mucosa is extremely difficult to differentiate from Ulcerative colitis, unless Histopathological examination is done which shows giant cells in Crohn's disease. (3) Radiology - Ba meal and follow through , the characteristic features are - (a) Skip lesion. (b) Ironed out Valvulae Conniventis. (c)Absence of peristalsis and lead pipe like segments.(d) Longitudinal and transverse fissures projecting outside in the bowel wall giving cobble stone mucosal pattern. (e) Constriction of terminal ileum, narrow stricture.When longer length of ileum is involved then string sign of Kantor is seen. (f) Dilatation of proximal ileum. Sinogram- In enterocutaneous fistula. CT Scan for intraabdominal abscesses.
Differentiation from Ulcerative Colitis.- The following features differentiate Crohn's disease from UC -
(1) Severity of pain, intestinal colicy pain of Crohn's disease.
(2) Absence of blood in stools.
(3) Palpable mass.
(4) Intestinal Obstruction.
(5) Small bowel involvement.
(6) Fistulae and perianal abscess in rectal and anal involvement.
(7) Segmental pattern of involvement.
(8) Aphthous leniar ulcers.
(9) Full thickness involvement of bowel wall.
(10) Sarcoid type of giant cells in H P R.
Preoperative differentiation is important as Total Proctocolectomy , .as done in ulcerative colitis will not eradicate the disease.

Medical therapy - Mild to moderate type of cases are treated on outpatient basis. But severe symptomatic cases require hospitalisation. (1) The drug of choice is Sulfasalazine. Starting with 1Gm daily and increasing to 4 Gms daily until total remission is achieved then the drug is tapered off. (2) Low dose Metronidazole is also effective. (3) Prednisolone at a dose of 60 Mgs per day in 3 to 4 divided dose for 10 to 14 days then tapered off. (4) Immunosuppressive agents - Azathioprim, 6 Merkaptopurine.
Surgical therapy - It is indicated in (a) Recurrent Obstruction. (b) Perforation. (c) Adhesion and obstruction. (d) Intestinal fistula. (e) Perianal disease. (f) Failure of medical treatment. (g) Malignant changes. Surgical resection will not cure the Crohn's Disease. So surgery should be limited to treatment of complication of the disease. Because by removing a segment of diseased bowel does not cure the patient of Crohn's disease as proctocolectomy cures a patient of Ulcerative Colitis.The aim of the surgical treatment is to remove as little bowel as it is necessary to correct the problem. Patients with single, short segment of Crohn's disease responds best to surgery. Ileocoecal anastomosis of a patient having had previous ileocaecal resection for Crohn's disease, recurrent disease is seen on the ileal side of the anastomosis. Stricturoplasty is the surgical option in stricturing Crohn disease. Recurrence rate after surgery is high- 30% after 5 Years, 50% after 10 Years and 70% after 15 Years. The aim of surgery is to remove grossly diseased bowel and to preserve as much normal appearing bowel as possible. If terminal ileun is removed patient should be investigated for B 12 deficiency every 6 months. Most patient will require B 12 injection every month.

Differentiation of Ulcerative Colitis From Crohn's Disease.
Ulcerative Colitis. Crohn's Disease.
Site of disease. Colon only. Any part of GI Tract.
Distribution. Diffused. Focal (Segmental) skip areas
Anatomical plane. Mucosa and Submucosa. Transmural.
Colonic appearance. Diffused friability. Focal / Apthous ulcers Cobble stone appearance. Linear ulcers with normal surrounding mucosa.
Crypt architecture. Distorted (crypt abscess.) Normal or focally distorted.
Inflammation. Acute and Chronic. Normal or acute/chronic
Epithelioid granulomas. Never. Present.
Complications. Internal fistulae/abscess never or rarely occurs. Fistulae and abscess can occur.
Strictures. Uncommon. Common.
Cancer risk after long standing disease. + + + + + +