Crohn's & ColitisDrug treatment of ulcerative colitis aims to reduce inflammation, allowing the colon to function more normally. The Troubling Symptom You Can? Please enter a valid email address. Talk to your doctor about which ulcerative colitis medication is co,itis for you. Ulcerative colitis — Complementary and Alternative Medicine Guide. University of Maryland Medical Center.
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The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon.
Intravenous corticosteroids are the mainstay of therapy. Medical rescue therapies include intravenous cyclosporin and infliximab.
Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy. However these figures are for specialist centers and at peripheral centers the mortality figures may be higher. The objective of this review is to provide in depth information for what can be categorized as a gastrointestinal medical emergency with the hope that informed clinical practices may translate to superior patient care at tertiary as well as peripheral centers treating ulcerative colitis.
This review provides time bound framework, which looks at stepwise management of acute severe ulcerative colitis and explores the recent concepts of choice between biologics and cyclosporin colon rescue therapies in case of steroid refractory disease.
The term acute severe colitis is preferred over fulminant colitis because the term fulminant is not well defined. It was coined in when it meant that single attack of UC could lead to mortality within 1 year[ 4 ], which is no longer relevant today.
Toxic megacolon is presence of megacolon with signs of systemic toxicity fever, tachycardia, hypotension, leukocytosis. At least 3 stool samples for Clostridium difficile C. A plain abdominal X-ray should be done to exclude megacolon. Plain radiograph can also provide information about the extent of disease and can also predict response to treatment.
The distal distribution of fecal residue can provide a rough estimate of disease extent as it correlates with the proximal extent of disease[ 10 ]. The predictors of poor response to treatment on a plain abdominal radiograph are presence of mucosal islands which are small, circular opacities that represent residual mucosa isolated by surrounding ulceration, or presence of more than two gas-filled loops of small bowel[ 11 ].
Flexible unprepared sigmoidoscopy with minimal air insufflation should be performed to confirm the diagnosis and exclude superimposed infection, especially cytomegalovirus CMV colitis[ 12 ]. Endoscopic markers of severe disease activity include hemorrhagic mucosa with deep ulceration, mucosal detachment on the edge of these ulcerations, and well like ulcerations[ 13 ]. In addition to specific therapy these supportive measures are very important in the management of patients with acute severe UC.
Enteral nutrition is most appropriate and is preferred over parenteral nutrition as it is associated with significantly fewer complications than parenteral nutrition in acute colitis[ 14 ]. There is no evidence that bowel rest with parenteral nutrition alters the outcome[ 15 ]; 4 Flexible unprepared sigmoidoscopy and biopsy should be done to confirm the diagnosis of acute severe UC and exclude infections[ 16 ] such as CMV.
Presence of active CMV infection is indicated by presence of cytomegalovirus inclusion bodies on colonic biopsies. However inclusion bodies are not very frequent even in patients with active disease with a sensitivity as low as Special immunohistochemical staining against immediate early antigens of CMV increases the diagnostic sensitivity of histologic examination for CMV.
Presence of active CMV disease requires treatment with ganciclovir, especially if the patient is slow to respond to conventional therapy; 5 Stool analysis in atleast 3 stool samples to exclude co-existing C. Therefore prophylaxis with subcutaneous low molecular weight heparin is indicated to reduce the risk of thromboembolism; 7 Topical corticosteroids or mesalazine may be administered if patient can tolerate and is able to retain them, although there have been no systematic studies in acute severe colitis; 8 Antibiotics are indicated only if infection is suspected or immediately prior to surgery.
Corticosteroids are the mainstay of therapy for acute severe UC. Treatment duration is usually limited to 7 to 10 d; continuing corticosteroid treatment beyond that period carries no additional benefit[ 25 ]. Truelove and Jewell published the first clinical trial of intravenous corticosteroids for acute severe UC in [ 26 ]. In another prospective study by Lindgren et al[ 27 ] which included 97 episodes of severe UC, the following mathematical model was devised to predict colectomy: Algorithm for treatment decisions for patients with acute severe ulcerative colitis on intensive steroid therapy.
Therefore regular assessment of response to steroids is of paramount importance in treating patients with acute severe UC. In patients who respond to steroids, oral steroids should be started after d of intensive therapy. Ten year follow up of patients of Oxford cohort categorized at day 7 of intensive therapy.
There are several other studies which have predicted response to steroids in acute severe UC. In another study by Ananthakrishnan et al[ 30 ], anemia, malnutrition, need for blood transfusion and total parenteral nutrition would independently predict colectomy. Two controlled clinical trials established the efficacy of intravenous cyclosporin fungal calcineurin inhibitor as medical rescue therapy for acute severe UC not responding to intravenous corticosteroids. The trial was terminated early for ethical reasons because of marked response to cyclosporin.
Of nine placebo treated patients 5 patients were crossed over to cyclosporin and all five responded. Therefore cyclosporin monotherapy may be preferred over steroids in patients who have high chances of side-effects with steroids including patients with osteoporosis, poorly controlled diabetes and those who are susceptible to steroid-psychosis.
However, one of the major limitations associated with cyclosporin use is its side effect profile. The short-term side effects are a cause of concern because cyclosporin is generally used as bridge to immunomodulators. Cyclosporin therapy in UC is associated with a mortality rate of approximately 1. Therefore, following points should be considered before starting cyclosporin therapy.
Azathioprine should be started along with oral cyclosporin. Cyclosporin should be stopped after 3 mo. Algorithm for medical rescue therapy after failure of response to intravenous steroids. Infective complications with cyclosporin can be avoided by minimizing concomitant immunosuppressants and by using prophylactic antibiotics when indicated.
Immunomodulators when used with cyclosporin can decrease the colectomy rate, thus improving the long term efficacy of cyclosporin. In a study by Cohen et al[ 41 ] probability of avoiding colectomy at long-term follow-up 5.
Further studies in this regard have shown that in patients already on immunomodulators at the time of admission with acute severe UC, the likelihood of needing a colectomy following treatment with cyclosporin is higher than among those in whom immunomodulators are started after admission[ 40 ].
Long term response rates to cyclosporin[ 38 ]. In patients who are already on thiopurine at the time of admission, the outcome with cyclosporin would be less favourable and other medical options or surgery needs to be considered.
Infliximab the chimeric monoclonal antibody against tumor necrosis factor TNF alpha has been found to have a favorable response in patients with steroid refractory acute severe UC. Four out of these 6 patients were in long term remission at median follow up of 5. The maximum benefit of infliximab was seen in patients with moderately severe disease than in those with most severe disease. Prior exposure to thiopurines does not seem to affect the outcome of patients treated with infliximab[ 43 ].
Screening for infections and immunization history should be obtained prior to initiating infliximab therapy. Screening tests which need to be done include hepatitis B serology, HIV serology, chest radiograph and tuberculin skin test or Interferon gamma release assays for latent tuberculosis. Long term follow up data up to 3 years in infliximab treated severe UC patients are available.
However, there are few trials of adalimumab in moderate to severe active UC which showed efficacy of adalimumab over placebo. Reinisch et al[ 48 ] showed that adalimumab induced remission in In another study Sandborn et al[ 49 ], in a similar group of patients showed efficacy of adalimumab over placebo Before the landmark randomized trial CYSIF Cyclosporin With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis between cyclosporin and infliximab there was limited evidence to suggest any difference in efficacy of cyclosporin and infliximab.
In a retrospective review of two cohorts 43 treated with cyclosporin and 49 treated with infliximab there was lower short term colectomy rate in the cyclosporin group[ 50 ]. Patients who responded at day 7 received oral azathioprine and tapered steroids from day 8. There was no clear evidence of superiority of any one therapy over other. Therefore choosing between cyclosporin and infliximab depends upon physician and patient preferences as both appear to be equally efficacious in the setting of acute severe colitis.
In cases of non-response to infliximab or cyclosporin, switching to either therapy is associated with significant morbidity and mortality and is not recommended. In the largest study of 86 patients on this aspect, 65 patients were administered infliximab after cyclosporin and 21 patients had cyclosporin after infliximab. Tacrolimus is also a calcineurin inhibitor with mechanism of action similar to that of cyclosporin.
However, further case series have shown results similar to that of cyclosporin[ 54 , 55 ]. Toxic megacolon may be defined as colonic dilatation of more than 5. Risk factors include dyselectrolytemia, full bowel preparation and medications antidiarrheal, anticholinergic, and opiods [ 6 ].
Earlier identification of this condition, prompt institution of medical therapy nil per oral, intravenous broad spectrum antibiotics, fluid and electrolyte management, and intensive therapy and low threshold of surgery in cases of non-response to medical therapy within 48 h will decrease the morbidity and mortality of this condition. Other complications include perforation which is the most serious complication of severe UC.
Risk factors include inappropriate total colonoscopy and delaying treatment of toxic megacolon. Diagnosis of perforation can often be delayed as abdominal signs can be masked when patient is on steroids. Therefore, patients with severe UC should be monitored closely for abdominal signs and on the slightest suspicion abdominal radiographs should be obtained. Other complication includes severe hemorrhage. Surgery is the final option for patients with severe UC not responding to medical therapy.
Other indications for surgery include toxic megacolon, perforation and severe haemorrhage. The decision for surgery should not be delayed as this increases the morbidity and mortality of surgery. In another study from Oxford, higher surgical complication was noted if surgery was delayed beyond 8 d of medical therapy[ 28 ].
Therefore management of severe UC requires close collaboration between surgeon and gastroenterologist so that appropriate decisions can be taken without delay. Most centers advocate a 3 step surgery in emergency setting. The surgical procedure of choice in acute setting is sub-total colectomy and ileostomy, with the rectum left in situ. The whole of rectum and inferior mesenteric artery should be preserved, which facilitates further surgery.
Subtotal colectomy is a safe procedure even in critically ill patients[ 57 , 58 ] and will relieve the patient from burden of severe colitis, thus allowing the patient to normalise health and nutrition. Reconstructive surgery is best performed approximately 6 mo after primary surgery[ 59 ]. The second step consists of ileal pouch formation and defuctioning temporary ileostomy.
In the final step ileal pouch anal anastomosis IPAA is done restoring normal continuity. There appears to be a strong association of prolonged use of immunosuppression and poor wound healing after surgery which may manifest as wound dehiscence, infection following intestinal leak or a pelvic abscess following anastomotic leak. Long-term preoperative steroid use has been found to be a significant risk factor for anastomotic leak.
Immunosuppressive agents azathiopurine and 6-mercaptopurine have not been associated with increased postoperative complications. When used alone, cyclosporin has not been associated with increased postoperative complications. The use of infliximab IFX and its impact on postoperative course is debatable and is a subject of intense interest.
The first report came from Mayo Clinic[ 60 ] which included a retrospective survey of 47 patients who received preoperative IFX and who did not.