Current Concepts in Treatment of Inflammatory Bowel Diseases

INTRODUCTION:

Inflammatory Bowel Disease (IBD)include Ulcerative colitis and Crohn's disease. I am sure every (or the most) readers of this article will agree that sometimes they are very difficult to treat and maintain in remission. This paper deals with the treatment of IBD as we have known it in the past, the extra we know now and what advances are being made as we enter the new millennium.

Both are characterised by relapses and remissions. Colitis is a purely mucosal disease and in Crohn's the inflammation involves the full thickness of the bowel wall. In ulcerative colitis the disease process is restricted to the colon either in total or in parts, i.e., (proctits, proctosigmoiditis, left-sided colitis and so on). Crohn's disease can affect any part of the G.I. tract and is featured by skip lesions.

TREATMENT OF IBD:

AIM of treatment includes the following: Symptomatic relief, Healing of inflammation, Maintaining remission

Symptomatic treatment: Diarrhoea in colitis (U.C. or C.D.) can be mild, (<3stools/day) moderate (3-6/stools/day) or severe (>6 stools/day). Anti-diarrhoeals such as Loperamide and Codeine phosphate have a place in the control of symptoms in the mild and moderate disease. However in patients with severe disease, more especially if it is colonic, anti diarrhoeals should be discouraged as this can sometimes lead to toxic dilatation. Blood loss and anaemia are treated with oral iron if mild. Severe anemia requires hospitalization and blood transfusion. Abdominal pain can be severe, especially in Crohn's disease and generally settles with mild analgesia. Codeine is best avoided as it can constipate the patient especially in patients with right-sided colitis.

Specific treatment: When the patient presents with symptoms of diarrhoea with blood loss he or she has active relapse. The disease process needs to be assessed and classified as mild moderate or severe and drug therapy instituted described as follows:

Severe attack: The patient needs to be hospitalised and is invariably toxic, manifested as pyrexia, tachycardia, anaemia and dehydration with low serum albumin and electrolyte imbalance. Blood transfusion and intravenous fluids and electrolytes as appropriate should be administered. Intensive nursing care includes regular abdominal girth measurement, daily chart of blood loss and diarrhoea. Other investigations should include regular blood analysis for haemoglobin, WBC and differential count including platelet count, urea as well as ESR and C-reactive protein.

Drug therapy: Corticosteroids are the main stay therapy in the acute relapse of both diseases. In acute stage the drug is given i.v. as hydrocortisone in high doses, 100 mg six or eight hourly. At the same time steroids are also administered as enema. As the patient shows clinical improvement the drug is changed to oral prednisolone 40mg daily for a week and gradually reduced as the patient improves and stopped over several weeks. Corticosteroids have no role in the maintenance of remission. Recent clinical studies have conclusively proven the efficacy of the immunosuppressive drug Cyclosporin in patients who continue to deteriorate both clinically and biochemically. The drug is administered intravenously at a dose of 4mg/kg body weight. The drug needs to be used cautiously because of adverse effects like hypertension, renal failure, convulsion as well as pneumocystis infection. It is therefore mandatory to regularly monitor the patient with chest x-ray and blood cultures as indicated as well as serum magnesium and lipids ideally prior to cyclosporin therapy. Some patients respond remarkably and when well enough to be discharged should be continued on oral cyclosporin in a low dose or another immunosuppressive drug as Azathioprine. Those who fail to respond to such intensive treatment or those who develop complications as toxic dilatation or haemorrhage should be referred for surgery without delay.

Maintenance Therapy: 5-Amino Salicylic Acid compounds (5-ASA) have almost replaced Sulphasalazine in the treatment of colitis. The 5-ASA drugs in higher doses have been shown to be equally effective in mild to moderate disease activity in both U.C. and C.D

All these compounds are available for topical usage as retention enemas and foams as well as suppositories. These are very valuable as adjuncts with oral preparations for purely left sided and limited colonic disease.

IMMUNOSUPPRESSIVE DRUGS:

1. The value of cyclosporin in acute colitis has already been mentioned. The drug has not been shown to be effective in Crohn's disease or as topical enemas but further studies in this direction should be forth coming.

2. AZATHOPRINE: This is a very well tried drug in IBD. It is indicated in steroid dependency. The dose in IBD is2.5mg/Kg body weight. Weekly blood WCC and platelet count needs to be done. Once the patient is able to tolerate the drug it can be given as a maintenance drug but monthly monitoring of blood and platelet counts is essential. Azathioprine has no value in acute Crohn's disease but useful in perianal disease as well as in healing fistulous disease. Available studies have shown that the drug is capable for maintaining remission in UC for about three years.

3. ANTIBIOTICS: Initial trials with certain antibiotics did not show any effectiveness in ulcerative colitis. More recently controlled trails have shown that Ciprofloxacin is effective. Similarly in Crohn's disease Metronidazole and Ciprofloxacin in combination are used effectively in the control of acute symptoms.

RECENT THERAPEUTIC ADVANCES:

Budesonide: a steroid with rapid metabolic pathway through the liver. Its advantage is that its toxic side effects are significantly lower than prednisolone. This drug, manufactured as pH dependant, terminal ileal release capsules, has been shown to be very effective in terminal ileal Crohn's disease (dosage being 9mg daily for six weeks). The drug has not been shown to be effective for maintenance therapy. Similarly Budesonide enema is useful in left sided IBD, but has very little preferential advantages to other topical enemas

Both UC and Crohn's are now considered genetic diseases in as much they share several of the features of autoimmune disorders. The genetic predisposition of Crohn's is perhaps better established and is different from that of ulcerative colitis. The HLA region on chromosome 6 may contain ulcerative colitis gene and the region on chromosome 16 for Crohn's disease. Other implicated genes include chromosomes 2,3,7 and 12. It is therefore an encouragement to the gastroenterologists and the patients that gene therapy is a remote but a distinct possibility.

Future includes targeting therapy on inflammatory mediators i.e. pro-inflammatory antagonists as well as anti-inflammatory agonists. One such compound, tumor necrosis factro-aplha antagonist is found to be very promising in Crohn's Other areas of target would include luminal microflora, nutrition and diets and immune response in general. It is noteworthy that Crohn's improves by stopping smoking and ulcerative colitis is a non smoker's disease we have recently shown that nicotine, given as skin patches or enemas, has helped patients with colitis .In conclusion we are entering an era when an organised approach to the therapy of IBD is taking place. It will not be too long before we cure the disease. (I am an optimist!).