Treatment of active ulcerative colitis
Treatment is determined by:
• the extent of disease
• the severity of the attack.
Knowledge of the extent of disease is particularly important in relation to the feasibility of effective topical therapy, while the severity of the attack defines not only the optimal type and route of therapy, but also whether the patient can be safely treated as an outpatient or needs urgent hospital admission.
Who needs hospital admission? Immediate admission is required for those with acute severe attacks of ulcerative colitis, defined primarily by clinical features (see Chapter 2). These include six or more bloody diarrheal stools daily, pyrexia and tachycardia (more than 90 beats/minute). Such patients will usually be systemically unwell, may be anemic and may have lost weight; very ill patients may have abdominal tenderness and/or distension.
The decision to admit does not usually depend on the results of blood or other tests of disease severity, though these will often be abnormal (see ‘Blood tests’, pages 44–6).
It is also advisable to admit less sick patients who have not responded as outpatients to 2 weeks’ treatment with oral prednisolone (see ‘Active left-sided or extensive ulcerative colitis’, pages 99–100). Since the initial attack of ulcerative colitis is more dangerous than subsequent ones, the threshold for admission should be lowered in those presenting for the first time with bloody diarrhea.
Inpatient management of acute severe ulcerative colitis
General measures. These patients should be admitted immediately to a gastroenterology ward for close joint medical, surgical and nursing care (Table 7.1). Early involvement of the nutrition team and of a stoma therapist in those who may need surgery is important. All patients undergoing a severe attack of ulcerative colitis need to be kept fully informed of their treatment and its likely outcome; they need to be aware from the outset that they have a 1 in 4 chance of needing an urgent colectomy during their admission.
TABLE 7.1 Principles of inpatient management of acute severe ulcerative colitis |
General measures Explanation, psychosocial support • physicians, specialist nurses • patient support groups Specialist multidisciplinary care • physicians, surgeons, nutrition team, nurses, stoma therapist, counselor |
Establishing the diagnosis, extent and severity Clinical evaluation Complete blood cell count, C-reactive protein, albumin, liver function tests, magnesium, cholesterol, amebic serology, CMV IgG Stool microscopy, culture, Clostridium difficile toxin Flexible sigmoidoscopy and biopsy Plain abdominal X-ray |
Monitoring progress Daily clinical assessment • abdominal examination (twice daily) • stool chart • 4-hourly temperature, pulse Daily complete blood cell count, C-reactive protein, urea and electrolytes, albumin Daily plain abdominal X-ray |
Supportive treatment Intravenous fluids, electrolytes, blood transfusion Nutritional supplementation Subcutaneous heparin Avoid antidiarrheals (codeine, loperamide, diphenoxylate), opiates, NSAIDs |
Specific treatments Medical • intravenous (hydrocortisone or methylprednisolone) then oral corticosteroids (prednisolone) • continue with oral 5-ASA in patients already taking it; otherwise start when improvement begins • antibiotics for very sick febrile patients, or when infection is suspected • for patients not responding to steroids at 4–7 days, consider: – intravenous then oral ciclosporin (cyclosporine) (with trimethoprim–sulfamethoxazole prophylaxis) or – infliximab Surgical (for non-responders at 5–7 days, acute colonic dilatation, perforation, massive hemorrhage) • panproctocolectomy with ileoanal pouch or permanent ileostomy • subtotal colectomy with ileorectal anastomosis (rarely) |
5-ASA, 5-aminosalicylate; CMV, cytomegalovirus; Ig, immunoglobulin; NSAIDs, non-steroidal anti-inflammatory drugs. |
Establishing the diagnosis, extent of disease and its severity requires a carefully targeted history and appropriate investigations (see Chapter 4) in those presenting for the first time. In patients with established ulcerative colitis, these procedures are required to exclude infection and to assess disease extent (if not already known) and severity.
Clinical evaluation. In patients with established ulcerative colitis, direct questions about stool frequency, consistency and urgency, overt blood content, abdominal pain, malaise, fever and weight loss indicate the severity of the attack. External examination should include assessment of general health, pulse rate and temperature, as well as a check for anemia, fluid depletion, weight loss, and abdominal tenderness or distension.
The differential diagnosis may also need evaluation in those presenting with bloody diarrhea for the first time (see Table 4.1). Abrupt onset with fever, vomiting, epidemic or contact history and/or recent foreign travel suggests infective colitis, even in those with pre-existing ulcerative colitis. Cytomegalovirus (CMV) should be considered, particularly in patients known to be immunosuppressed. Clostridium difficile infection is a mimic as well as a common concomitant of attacks of ulcerative colitis, with or without previous antibiotic exposure, while non-steroidal anti-inflammatory drugs (NSAIDs) may cause either a relapse of established IBD or de novo colitis (which usually remits rapidly on NSAID withdrawal).
In patients presenting for the first time, non-smoking or recent cessation of smoking increases the likelihood of ulcerative colitis, while previous abdominal or pelvic irradiation make radiation colitis a strong possibility. Ischemic colitis usually shows sudden onset in older people with other features of vascular disease, and often causes marked abdominal pain as well as bloody diarrhea. The very rare Behçet’s enterocolitis may be suggested by a history of cyclic oral and genital ulceration, uveitis, erythema nodosum, pathergy (the formation of pustules at the site of minor trauma, such as venepuncture) and/or arthropathy.
Blood tests are better for establishing the activity of ulcerative colitis than for making the diagnosis or identifying its extent (see Chapter 4). The best laboratory measures of disease activity in ulcerative colitis are hemoglobin, platelet count, C-reactive protein and serum albumin. For recent travellers, serology as well as stool samples should be requested (for amebiasis, strongyloidiasis and schistosomiasis). It is helpful to check CMV (immunoglobulin [Ig]G) serology on admission: if this is negative, CMV-induced colitis need not be considered if the patient fails to respond to steroid therapy. Serum magnesium and cholesterol should be checked in case ciclosporin (cyclosporine) is needed (see Chapter 5).
Sigmoidoscopy and rectal biopsy. Cautious rigid or flexible sigmoidoscopy and biopsy in the unprepared patient, and without excessive air insufflation, provides immediate confirmation of active colitis. Full colonoscopy may cause colonic perforation and dilation and should be avoided in acute severe ulcerative colitis.
Monitoring progress. Progress is monitored by twice-daily clinical assessment, including:
• abdominal examination, particularly by percussion, for gaseous distension, loss of hepatic dullness (which may indicate free gas in the peritoneal cavity) and peritoneal irritation
• stool chart (recording frequency, consistency, presence of overt blood and urgency)
• 4-hourly measurement of temperature and pulse.
Blood count, C-reactive protein, routine biochemistry and plain abdominal X-ray should be undertaken daily in sick patients (see Table 7.1).
Intravenous fluids and blood. Most patients require intravenous fluids and electrolytes, particularly potassium, to replace diarrheal losses. The serum potassium concentration should be maintained at or above 4 mmol/L (4 mEq/L), since hypokalemia may predispose to colonic dilatation. Blood transfusion is usually recommended if the hemoglobin level falls below 6.2 mmol/L (10 g/dL).
Nutritional support. Patients can usually eat normally, with liquid protein and calorie supplements if necessary. Very sick patients, many of whom will undergo surgery, may need enteral or parenteral nutrition.
Anticoagulation. Because active ulcerative colitis is associated with a high risk of venous and arterial thromboembolism, patients should be given prophylactic subcutaneous heparin (e.g. low-molecular-weight heparin, 3000–5000 units daily). Heparin does not appear to increase rectal blood loss, even when given intravenously.
Drugs to avoid are antidiarrheal (codeine phosphate, loperamide, diphenoxylate), opioid analgesic, antispasmodic and anticholinergic drugs, as well as NSAIDs. If mild pain relief is needed, oral paracetamol (acetaminophen) appears to be well tolerated, while severe pain suggests colonic dilatation or perforation needing urgent evaluation and/or intervention.
Drug therapy. A possible management pathway is shown in Figure 7.1. Corticosteroids remain the cornerstone of specific medical treatment for acute severe ulcerative colitis. Aminosalicylates and antibiotics have minor roles. Ciclosporin or infliximab are useful in steroid-refractory patients. However, oral azathioprine and mercaptopurine (MP) are too slow to work in those with severe steroid-refractory attacks.
Corticosteroids. Hydrocortisone, 300–400 mg/day, or methylprednisolone, 40–60 mg/day, are given intravenously. There is no advantage in giving higher doses, although continuous infusion may be more effective than once- or twice-daily boluses. Corticosteroid drip enemas (e.g. prednisolone, 20 mg, or hydrocortisone, 100 mg in 100–200 mL water given rectally via a soft catheter twice daily with the patient in the left lateral position) are sometimes given in addition to intravenous steroids, but their value is unproven.
Every patient’s progress needs careful daily evaluation by an experienced clinician able to institute any necessary management changes promptly. About 70% of patients who receive corticosteroids improve substantially in 5–7 days. They are then switched to oral prednisolone, 40–60 mg/day, the dose being tapered to zero over 2–3 months. However, those patients not showing a clear reduction in stool frequency and C-reactive protein after 3 days of intravenous corticosteroids need rescue therapy with ciclosporin or infliximab (see below) or urgent colectomy (see Chapter 9).
Figure 7.1 General principles of managing acute severe ulcerative colitis. In practice, each step will depend on detailed daily evaluation of the patient (see text) and discussion of the options under consideration. 5-ASA, 5-aminosalicylate; CMV, cytomegalovirus; IV, intravenous; MP, mercaptopurine; UC, ulcerative colitis.
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