CROHN’S DISEASE (REGIONAL ENTERITIS)

Epidemiology

                       Most common in north america and northern europe, with incidence of 05 per 100,000. In the UK 56 per 100,000 is reported. It is slightly more common in women than men but most commonly diagnosed in the young patients between the age of 25 and 40 years.

Aetiology

Crohn’s disease has some features suggesting chronic infection, with no causative organism has ever been found. Focal ischaemia has also been postulated as a causative factor, possibly arising from vasculitis. Smoking increasing the risk three folds. Genetic factors are thought to play a part. About 10% of the patients have a first degree relatives with the disease. There is an association with ankylosing spondylitis. It mostly manifests in the ileum.

Pathogenesis

                      It is thought that an increase in the permeability of the mucous membrane. This leads to increase passage of antigen, which are thought to induce a cell mediated inflammatory response. This results in release of cytokine such as interleukine-2 and TNF which co-ordinate local and systemic response. It is thought that there is defect in supressor T-cells which usually act to prevent escalation of the inflamatory process.

Pathology

                 Ileal disease is the most common accounting for 60% of cases. 30% cases are limited to the large intestine and 10% are more proximal small intestine. Anal lesions are common. Resection  specimens show a fibrotic thickening of the intestinal wall with a narrow lumen. There is usually dilated gut just proximal to the stricture and in the strictured area there is  deep mucosal ulceration with linear or snake like pattern. The transmural inflamation leads to adhesions inflamatory masses with mesenteric abscess and fistula into the adjacent organs. The serosa is usually opaque. There is thickening in the mesentery and the mesenteric lymph nodes are enlarged. This condition is discontineous with inflamed areas seperated from normal intestine. So called skip lesion. Under the microscope there are focal areas of chronic inflamation involving all layers of the intestinal wall. There are non-caseating giant cell granuloma but these are found  in 60% of patients. They are most common in ano rectal disease. The earliest mucosal lesions are discrete aphthus ulcers.

Clinical features

                            Depends upon the area of involvement.

Acute crohn’s disease

                                   Acute crohn’s disease occurs in only 5% cases. Symptoms and signs resemble those of acute appendicitis but there is usually diarrhoea preceding the attack. Rarely there could be a free perforation of the small intestine resulting in a local or diffuse peritonitis. Acute colitis with or without mega colon can occur in crohn’s disease but less common than in ulcerative colitis.

Chronic crhohn’s disease

                                            Mild diarrhoea extending over many months occuring in bouts accompanied by intestinal colic. Patient may complain of pain, particularly in right iliac fossa a tender mass may be palpable. Intermittent fever, secondary anaemia and weight loss are common. A perianal abscess or fissure may be the first  presenting feature of crohn’s disease, the cause is often an infected anal crypt associated with concomittent diarrhoea.

   After months of repeated attack with acute inflamation, the affected area of the intestine begins to narrow with fibrosis causing obstructive symptoms.With progression of the disease, adhesions and transmural fissuring, intra-abdominal abscess and fistula tracts can develop.

1)           Entero-enteric fistula can occur with adjacent small gut loop or pelvic colon and entero-vesical fistula may cause repeated urinary tract infection and pneumaturia.

2)           Entero-cutaneous fistula- rarely occur spontaneously and usually follow previous surgery.

Anal disease

                     In presence of active disease, the perianal skin appears bluish. Superficial ulcer with undermined edges are relatively painless and can heal with bridging of epithelium. deep cavitating ulcers are usually found in upper anal canal, they are usually painful and can cause perianal abscess and fistula. The most distressing feature of anal disease is sepsis from secondary abscess and perianal fistula.

Investigations

                      Complete blood count to exclude anaemia, fall of albumin, magnesium, zinc, seleneum specially in active disease.

                    Endoscopy

                                       Sigmoidoscopy- Ulceration in anal canal is readily seen. AS a result of the dis contineous nature of CD, there will be area of normal colon or rectum. The earliest appearance are aphthoid like ulcers surrounded by a rim of erythematous mucosa. These become larger and deeper with increasing severity of disease.

                        Imaging

                                     Ba enema will show similar features to those of  colonoscopy in the colon. THe best investigation of the small intestine is small bowel enema.

                           

Treatment

   Medical therapy:-

1)       Steroids-

Steroids are the mainstay of  treatment. These are effective in inducing remision in moderate to severe disease in 70-80% of cases. Steroids can also be used as topical agents in rectum with reduced systemic bio availability but long term uses can  cause  adrenal suppression. Patients suffering a relapse are treated with upto 40mg of prednisolone orally daily, supplemented by 5- ASA compounds in those patients with colonic involvement.

2)      Anti-biotics:

  Those who have symptoms and signs of a mass or an abscess are also treated with anti biotics. Metronidazole is used  especially in perianal disease.

Immunomodulary agent

    Azathioprine is used for its additive and steroid sparing effect and is now standard maintanance therapy. It is a purine analogue, which is metabolized to 6, mercaptopurine and works by inhibiting cell mediated events.  Cyclosporine acts by inhibiting cell mediated immunity.

Monoclonal antibody:-    Infliximab, the  murine chimeric monoclonal antibody directed towards TNF-alpha, target patients with severe, active disease who are refractory to conventional treatment and who are at high risk of surgical interventions.

Nutritional support 

Nutritional support is essential. Severely malnourished people way require intra venous feeding regimens. Anaemia, hypo proteinaemia  and electrolytes, vitamins, and metabolic bone problems must all be addressed.

Indication for surgery                                                  

·         Recurrent intestinal obstruction.

·         Bleeding

·         Perforation

·         Failure to medical therapy

·         Intestinal fistula

·         Fulminant colitis

·         Malignant changes

·         perianal disease

Surgery

·         Ileocaecal resection

·         Segment resection

·         Colectomy and ileo rectal anaestomosis

·         Emergency colectomy

·         Laparoscopic surgery

·         Temporary loop ileostomy

·         Procto colectomy

·         Strictureplasty

·         Anal disease is usually treated conservatively by simple drainage of abscess.