1. I NFLAMMATORY B OWEL D ISEASE

2. There are two forms of idiopathic inflammatory bowel disease (IBD): (a) Ulcerative Colitis, a mucosal inflammatory condition confined to the rectum and colon; (b) Crohn’s disease, a transmural inflammation of the gastrointestinal tract that can affect any part, from the mouth to the anus.

3. E TIOLOGY Infectious agents Viruses (e.g., measles) L-Forms of bacteria Mycobacteria Chlamydia Genetics Metabolic defects Connective tissue disorders Environmental Factors Diet Smoking (Crohn’s disease)

4. Immune defects Altered host suceptibility Immune-mediated mucosal damage Psychologic factors Stress Emotional or physical trauma Occupation Etiology

5. INFECTIOUS FACTORS Microorganisms are a likely factor in the initiation of inflammation in IBD. Patients with inflammatory bowel diseases have increased numbers of surface-adherent and intracellular bacteria. Microbes may elaborate superantigens, which are capable of global T-lymphocyte stimulation and subsequent inflammatory response.

6. G ENETIC FACTORS Genetic factors predispose patients to inflammatory bowel diseases, particularly Crohn’s disease. In studies of monozygotic twins, there has been a high concordance rate, with both individuals of the pair having an IBD (particularly Crohn’s disease). Also, first-degree relatives of patients with IBD had a 13-fold increase in the risk of disease.

7. IMMUNOLOGIC MECHANISMS With Crohn’s disease, the bowel wall is infiltrated with lymphocytes, plasma cells, mast cells, macrophages, and neutrophils. Similar infiltration has been observed in the mucosal layer of the colon in patients with ulcerative colitis. Inflammation in IBDs is maintained by an influx of leukocytes from the vascular system into sites of active disease. Many of the systemic manifestations of IBD have an immunologic etiology (e.g., arthritis or uveitis). IBD is responsive to immunosuppressive drugs (e.g., corticosteroids and azathioprine).

8. Potential immunologic mechanisms include both autoimmune and nonautoimmune phenomena.

9. PSYCHOLOGICAL FACTORS Mental health changes appear to correlate with remissions and exacerbations, especially of ulcerative colitis, but are not thought to be an etiologic factor.

10. DIET, SMOKING, AND NSAID USE Studies of increased intake of refined sugars or chemical food additives and reduced fiber intake have provided conflicting results regarding risk for Crohn’s disease. Smoking plays an important but contrasting role in ulcerative colitis and Crohn’s disease. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) can trigger disease occurrence or lead to disease flares.

11. P ATHOPHYSIOLOGY Ulcerative colitis and Crohn’s disease differ in two general respects: anatomic sites and depth of involvement within the bowel wall. The inflammatory response seen in IBD has also been blamed for the systemic complications seen in both Crohn’s disease and ulcerative colitis.

12. U LCERATIVE COLITIS Ulcerative colitis is confined to the rectum and colon, and affects the mucosa and the submucosa. In some instances, a short segment of terminal ileum may be inflamed; this is referred to as backwash ileitis. Unlike Crohn’s disease, the deeper longitudinal muscular layers, serosa, and regional lymph nodes are not usually involved. Fistulas, perforation, or obstruction are uncommon because inflammation is usually confined to the mucosa and submucosa.

13. The primary lesion of ulcerative colitis occurs in the crypts of the mucosa (crypts of Lieberkuhn) in the form of a crypt abscess. Other typical ulceration patterns include a “collar- button ulcer,” which results from extensive submucosal undermining at the ulcer edge. Ulcerative colitis can be accompanied by complications that may be local (involving the colon or rectum) or systemic (not directly associated with the colon).

14. Colonic perforation, however, may occur with or without toxic megacolon and is a greater risk with the first attack. Another infrequent major local complication is massive colonic hemorrhage. Colonic stricture, sometimes with clinical obstruction, may also complicate long-standing ulcerative colitis

16. HEPATOBILIARY COMPLICATIONS Approximately 11% of patients with ulcerative colitis are reported to have hepatobiliary complications with frequencies ranging from 5% to 95% in IBD patients overall. Hepatic complications include fatty liver, pericholangitis, chronic active hepatitis, and cirrhosis. Biliary complications include sclerosing cholangitis, cholangiocarcinoma, and gallstones.

17. JOINT COMPLICATIONS Arthritis commonly occurs in IBD patients and is typically asymmetric (unlike rheumatoid arthritis) and migratory, involving one or a few usually large joints. The joints most often affected, in decreasing frequency, are the knees, hips, ankles, wrists, and elbows.

18. OCULAR COMPLICATIONS Ocular complications including iritis, uveitis, episcleritis, and conjunctivitis occur in up to 10% of patients with IBD. The most commonly reported symptoms with iritis and uveitis include blurred vision, eye pain, and photophobia.

19. DERMATOLOGIC AND MUCOSAL COMPLICATIONS Skin and mucosal lesions associated with IBD include erythema nodosum,pyoderma gangrenosum, and aphthous ulceration.

20. C ROHN ’ S D ISEASE Crohn’s disease is best characterized as a transmural inflammatory process. The terminal ileum is the most common site of the disorder, but it may occur in any part of the GI tract from mouth to anus. Fistula formation is common and occurs much more frequently than with ulcerative colitis. Fistulae often occur in the areas of worst inflammation, where loops of bowel have become matted together by fibrous adhesions.

21. C OMPLICATION Systemic complications of Crohn’s disease are common, and similar to those found with ulcerative colitis. Arthritis, iritis, skin lesions, and liver disease often accompany Crohn’s disease. Renal stones occur in up to 10% of patients with Crohn’s disease

23. C LINICAL P RESENTATION Mild —Fewer than four stools daily, with or without blood, with no systemic disturbance and a normal erythrocyte sedimentation rate (ESR). Moderate —More than four stools per day but with minimal systemic disturbance. Severe —More than six stools per day with blood, with evidence of systemic disturbance shown by fever, tachycardia, anemia, or ESR of > 30. It is also important to determine disease extent; that is, which part of the colon is involved— rectum, descending colon only, or the entire colon.

24. C LINICAL P RESENTATION OF U LCERATIVE C OLITIS Signs and symptoms Abdominal cramping Frequent bowel movements, often with blood in the stool Weight loss Fever and tachycardia in severe disease Blurred vision, eye pain, and photophobia with ocular involvement Arthritis Raised, red, tender nodules that vary in size from 1 cm to several cm

25. Physical examination Hemorrhoids, anal fissures, or perirectal abscesses may be present Iritis, uveitis, episcleritis, and conjunctivitis with ocular involvement Dermatologic findings with erythema nodosum, pyoderma gangrenosum, or aphthous ulceration Laboratory tests Decreased hematocrit/hemoglobin Increased erythrocyte sedimentation rate Leukocytosis and hypoalbuminemia with severe disease

26. C LINICAL P RESENTATION OF C ROHN ’ S D ISEASE Signs and symptoms Malaise and fever Abdominal pain Frequent bowel movements Hemotachezia Fistula Weight loss Arthritis Physical examination Abdominal mass and tenderness Perianal fissure or fistula Laboratory tests Increased white blood cell count and erythrocyte sedimentation rate

27. RXRX These goals may relate to resolution of acute inflammatory processes, resolution of attendant complications (e.g., fistulas and abscesses), alleviation of systemic manifestations (e.g., arthritis), maintenance of remission from acute inflammation, or surgical palliation or cure.

28. Proper nutritional support is an important aspect of the treatment of patients with IBD, not because specific types of diets are useful in alleviating the inflammatory conditions, but because patients with moderate to severe disease are often malnourished either because the inflammatory process results in significant malabsorption or maldigestion, or because of the catabolic effects of the disease process.

29. Parenteral nutrition is an important component of the treatment of severe Crohn’s disease or ulcerative colitis. The use of parenteral nutrition allows complete bowel rest in patients with severe ulcerative colitis, which may alter the need for proctocolectomy. Parenteral nutrition has also been valuable in Crohn’s disease, because remission may be achieved with parenteral nutrition in about 50% of patients

30. Probiotics involves the reestablishment of normal bacterial flora within the gut by oral administration of live bacteria such as nonpathogenic Escherichia coli, bifidobacteria, lactobacilli, or Streptococcus thermophilus. Probiotic formulations have been effective in maintaining remission in ulcerative colitis

31. Although surgery (proctocolectomy) is curative for ulcerative colitis, this is not the case for Crohn’s disease.. For ulcerative colitis, colectomy may be necessary when the patient has disease uncontrolled by maximum medical therapy or when there are complications of the disease such as colonic perforation, toxic dilatation (megacolon), uncontrolled colonic hemorrhage, or colonic strictures. Colectomy may be indicated in patients with longstanding disease (greater than 8 to 10 years), as a prophylactic measure against the development of cancer, and in patients with premalignant changes (severe dysplasia) on surveillance mucosal biopsies

32. The major types of drug therapy used in IBD include aminosalicylates, corticosteroids, immunosuppressive agents (azathioprine, mercaptopurine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit TNF-α (anti-TNF-α antibodies).

33. Sulfasalazine, an agent that combines a sulfonamide (sulfapyridine) antibiotic and mesalamine (5- aminosalicylic acid) in the same molecule, has been used for many years to treat IBD. The active component of sulfasalazine is mesalamine. Aminosalicylates may block production of prostaglandins and leukotrienes, inhibit bacterial peptide-induced neutrophil chemotaxis and adenosine-induced secretion, scavenge reactive oxygen metabolites, and inhibit activation of the nuclear regulatory factor NF-κB.

34. Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative colitis and Crohn’s disease, given parenterally, orally, or rectally. Corticosteroids are believed to modulate the immune system and inhibit production of cytokines and mediators

35. Azathioprine and mercaptopurine are effective for long-term treatment of Crohn’s disease and ulcerative colitis. These agents are generally reserved for patients who are refractory to steroids, and they may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity

37. DRUGSDOSEADR Prednisolone40 mg/day Reduse in 4 -6 week Moon face,sleep and mood disturbance,dyspepsia. Sulfasalazine2 -4g/day in div dose Nausea,vomiting,abdominal pain,metalic taste,heamolytic aneamia. Azathioprine Mercaptopurine Methotrexate 2-2.5 mg/kg/day 1-1.5mg/kg/day 15 -25 mg once weekly Flu like symptom,nausea, diarrhoea, leukopenia,pancreatitis Nausea,vomiting,stomatitis Ciclosporin2-5mg/kg/dayTremour,headache,gum hyperplasia, hirsutism Metronidazole0.6 -1.5g/dayMetalic taste, glossitis,paraesthesia,urticaria.