Inflammatory bowel disease

13 Inflammatory bowel disease





Key points













Aetiology


The causative agents of IBD are largely unknown, although a number of factors are thought to play a role.



Environmental







Drugs


Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac have been reported to exacerbate IBD (Felder et al., 2000). It is thought this may result from direct inhibition of the synthesis of cytoprotective prostaglandins. Antibiotics may also precipitate a relapse in disease due to a change in the enteric microflora. The risk of developing Crohn’s disease is thought to be increased in women taking the oral contraceptive pill, possibly caused by vascular changes.




Appendicectomy


Appendicectomy has a protective effect in both Crohn’s disease and ulcerative colitis (Radford-Smith et al., 2002). It is unclear whether this protective effect is immunologically based or whether individuals who develop appendicitis and consequently have an appendicectomy are physiologically, genetically or immunologically distinct from the population that is predisposed to IBD.





Pathophysiology


In individuals with IBD, trigger factors typically cause a severe, prolonged and inappropriate inflammatory response in the gastro-intestinal tract and the ongoing inflammatory reaction leads to an alteration in the normal architecture of the digestive tract. Genetically susceptible individuals seem unable to downregulate immune or antigen non-specific inflammatory responses. It is thought that chronic inflammation is characterised by increased activity of effector lymphocytes and pro-inflammatory cytokines that override normal control mechanisms. Others, however, have suggested that IBD may result from a primary failure of regulatory lymphocytes and cytokines, such as interleukin-10 and transforming growth factor-β, to control inflammation and effector pathways. In Crohn’s disease, it is also thought that T-cells are resistant to apoptosis after inactivation. Non-pathogenic bowel flora appears to be an essential factor.



Disease location


The character and distribution, both macroscopic and microscopic, of chronic inflammation define and distinguish ulcerative colitis and Crohn’s disease. Table 13.1 shows the differences in location and distribution of ulcerative colitis and Crohn’s disease. Figure 13.1 details the histological differences.


Table 13.1 Location and distribution of ulcerative colitis and Crohn’s disease



































  Ulcerative colitis Crohn’s disease
Location Colon and rectum
40% proctitis
20% pancolitis
10–15% backwash ileitis
Entire gut (mouth to anus, rectal sparing)
45% ileocaecal disease
25% colitis only
20% terminal ileal disease
5% small bowel disease
5% anorectal, gastroduodenal, oral disease
Distribution Continuous, diffuse Often discontinuous and segmental ‘skip lesions’
  Full thickness (transmural)
No granulomas Granulomatous inflammation
Inflammation of mucosa  
Ulceration if fine and superficial Deep ulceration with mucosal extension
Fissures, fistulae and stricture Absent Common
Perianal disease Absent Present






Clinical manifestation


The clinical differences between Crohn’s disease and ulcerative colitis are described in Table 13.2.


Table 13.2 Clinical differences between ulcerative colitis and Crohn’s disease















































Symptom Ulcerative colitis Crohn’s disease
Prominent symptom Bloody diarrhoea Diarrhoea, abdominal pain, weight loss 30%, no gross bleeding
Fever ++ ++
Abdominal pain Variable ++
Diarrhoea +++ +++
Rectal bleeding +++ ++
Weight loss + ++
Sign of malnutrition + ++
Abdominal mass ++
Dehydration +++ ++
Iron-deficiency anaemia, raised CPR/ESR, hypoalbuminaemia ++ ++

CPR, C-reactive protein; ESR, erythrocyte sedimentation rate; +, the likelihood this symptom will be present; −, symptom absent in patient.



Crohn’s disease


The clinical features of Crohn’s disease depend largely on the site of the bowel affected, the extent, severity and the pathological process in each patient. Crohn’s disease tends to be more disabling than ulcerative colitis with 25% of patients unable to work 1 year after diagnosis. The predominant symptoms in Crohn’s disease are diarrhoea, abdominal pain and weight loss. Weight loss occurs in most patients, irrespective of disease location. Ten to twenty percent of patients will have weight loss greater than 20%. The main cause is decreased oral intake, although malnutrition is also common. There is a slight increase in mortality in patients with extensive Crohn’s disease.








Ulcerative colitis


Typical symptoms of ulcerative colitis include bloody diarrhoea (the most predominant symptom) with mucus, abdominal pain with fever, and weight loss in severe cases. The typical appearance of a patient diagnosed with Crohn’s disease is low BMI, malabasorption, weight loss and growth retardation. Frank blood loss is more common in ulcerative colitis than Crohn’s disease. The symptoms of ulcerative colitis are similar to Crohn’s colitis with patients being tachycardic, anaemic, febrile, fatigued, dehydrated and thin. Approximately 50% of patients with ulcerative colitis have some form of relapse each year, and severe attacks can be life-threatening. Up until the 1960s, one-third of ulcerative colitis patients died from the condition; with advances in medical and surgical treatment death is now extremely rare.







Extra-intestinal complications of IBD


Around 20–30% of patients with IBD will present with extra-intestinal manifestations. They are more commonly seen in patients where IBD affects the colon. Complications affect the joints, skin, bone, eyes, liver and biliary tree and are more common in active disease. Figure 13.3 highlights some of the extra-intestinal features of IBD.










Investigations


Radiological, pathological and clinical investigations help to confirm diagnosis, disease recurrence and response to treatment. Differential diagnoses of IBD include carcinoma, infection, drug-induced colitis, ischaemia, radiation damage, irritable bowel syndrome and diverticulitis.








Treatment of inflammatory bowel disease


At present there is no cure for IBD since the exact cause of the condition is unknown. A wide range of drugs and nutritional supplements are available to maintain the patient in long periods of remission in both Crohn’s disease and ulcerative colitis. However, surgical intervention will eventually become necessary when the patient relapses and fails to respond to drug therapy. Since the majority of people with IBD are diagnosed under the age of 30, effective treatment and avoidance of relapses is of paramount importance in this chronic long-term condition.



Nutritional therapy


Nutritional therapy can be considered as an adjunctive or primary treatment. Although a potential problem for all patients with IBD, patients with Crohn’s disease are at particular risk of becoming malnourished and developing a variety of nutritional deficiencies (Fig. 13.3). It is, therefore, important for patients to receive optimal nutrition and dietary manipulation as needed. Low-fibre diets help to reduce clinical symptoms of intestinal obstruction in Crohn’s disease (Fernandes-Banares et al., 1999). Functional and structural damage to the small bowel can cause malabsorption problems and occasionally patients may require a low-lactose diet. Patients with poor oral intake and loss of appetite often respond to supplemental enteral feeds. Enteral nutrition in the form of an elemental or polymeric diet can be used as primary therapy and is widely employed in paediatrics (Heuschkel and Walker-Smith, 1999).


Patients who have extensive small bowel resection may experience many nutritional deficiencies because of malabsorption. Iron depletion, hypoproteinaemia, deficiencies in water- and fat-soluble vitamins, trace elements and electrolytes may all occur and must be corrected using a suitable replacement regimen.


Where appropriate, and when enteral nutrition is not indicated or adequate, a total parenteral nutrition (TPN) regimen may be prescribed. Some patients receive concurrent enteral and parenteral feeding.



Drug treatment


The main goals of drug treatment are to treat acute attacks promptly and effectively, induce and maintain remission, limit drug toxicity, modify the pattern of disease, avoid and/or manage complications and select patients who will benefit from surgery. Morbidity and mortality can also be reduced by the prompt use of effective and appropriate drug therapy. The choice of drug and route of administration depends on the site, extent and severity of the disease together with the individual’s treatment history. Drug therapy is often required for many years and patient preference, acceptability and possible side effects not only affect choice but will impact on medication adherence. There is a need for therapeutic strategy and consistency in the management of patients with IBD.


Corticosteroids, aminosalicylates and immunosuppressive agents (immunomodulators) such as azathioprine are the mainstays of treatment. Immunomodulators are not licensed for use in IBD but are routinely used.


Modern advances in treatment, such as the use of humanised monoclonal antibody preparations and other biologic agents which modify the affected biochemical inflammatory pathways, now have a significant role in treatment of the disease. These are likely to be the main area of future development.


Other drugs such as antibiotics, for example, metronidazole, are helpful in some cases, while colestyramine, thalidomide, sodium cromoglicate, bismuth and arsenical salts, nicotine, lidocaine, sucralfate, new steroid entities, cytoprotective agents, aloe vera, probiotics and fish oils are rarely used. However, for some patients they provide alternative or supplemental therapy.


The choice of drug treatment is dependent on whether it is prescribed to induce remission or as maintenance therapy. The majority of patients are managed successfully as hospital outpatients or by their primary care doctor. Only severe extensive or fulminant disease requires hospitalisation and the use of parenteral therapy and/or surgical intervention. Oral medication can be given to most patients for maintenance of moderate disease.


The route of administration is a particularly important factor in IBD. In contrast to most other conditions, minimal systemic absorption and maximal intestinal wall drug levels are required with oral therapy. Several delivery strategies have been used to achieve this including the chemical modification of drug molecules, delayed and controlled-release formulations and the use of bioadhesive particles.


Disease confined to the anus, rectum or left side of the colon is more appropriately treated with rectally administered topical preparations where the drug is applied directly to the site of inflammation (Table 13.4).


Table 13.4 Comparison of commercially available preparations for rectal administration in inflammatory bowel disease















































Generic name (proprietary name) Formulation Site of release
Sulfasalazine (Salazopyrin®) Suppositories
Retention enema
Rectum
Transverse, descending colon and rectum
Mesalazine (Pentasa®, Salofalk®) Retention enema Transverse, descending colon and rectum
Mesalazine (Asacol®, Salofalk®) Foam enema Rectum and rectosigmoid colon
Mesalazine (Asacol©®, Pentasa®, Salofalk®) Suppositories Rectum
Prednisolone sodium phosphate (Predsol®) Retention enema
Suppositories
Transverse, descending colon and rectum
Rectum
Prednisolone sodium metasulphobenzoate (Predenema®) Retention enema Transverse and descending colon
Prednisolone sodium metasulphobenzoate (Predfoam®) Foam enema Rectum and rectosigmoid colon
Prednisolone sodium phosphate (Predsol®) Retention enema Transverse and descending colon
Hydrocortisone acetate (Colifoam®) Foam enema Rectum and rectosigmoid colon
Budesonide (Entocort©®) Retention enema Rectum and rectosigmoid colon

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Jun 18, 2016 | Posted by in PHARMACY | Comments Off on Inflammatory bowel disease

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