24th July 2023

Inflammatory Bowel Disease

Crohn’s disease and ulcerative colitis

Crohn’s disease and ulcerative colitis are coined under the umbrella term of Inflammatory Bowel Disease (IBD). They have many similarities, which can make differentiating them difficult. Some of the key differences used to distinguish the two conditions are summarised in the table below.

Table 1: Key differences between Crohn’s disease and ulcerative colitis

Investigations and diagnosis

Basic investigations for a patient presenting with suspected IBD include the following:

• Blood tests – FBC, U&Es, CRP, ESR, LFTs, haematinics, vitamin D
• Coeliac serology (for exclusion)
• Faecal calprotectin (may be raised in inflammatory bowel disease)
• Stool microscopy, culture and sensitivity

Further investigations consist of imaging and colonoscopy (with subsequent histology).
Crohn’s disease is associated with the following findings:

• Radiological:
  • Barium swallows demonstrate narrowing of lumen, features of ulceration and nodularity, and can give a “string sign” appearance in advanced disease
  • MRI with small bowel enterography (MRE) and CT with small bowel enterography (CTE) are also used
• Colonoscopy:
  • Macroscopic findings include skip lesions, cobblestone mucosa, and rectal sparing (will appear normal)
  • Microscopic findings include granulomas, focal inflammation of the lamina propria, crypt distortion

Ulcerative colitis is associated with the following findings:

• Radiological:
  • Abdominal x-ray shows proximal constipation, mucosal thickening, “thumbprinting” sign, and colonic dilation in severe disease
  • Barium enema is used to show shortening of the colon, and loss of haustra to give characteristic “lead pipe colon” appearance
  • CT and MRI show nonspecific thickening of the bowel wall, and are less sensitive compared to barium enemas for early disease
• Colonoscopy:
  • Macroscopically disease is confined to the colon and rectum, with continuous inflammation, pseudopolyps may be present
  • Microscopic findings include crypt atrophy, villous mucosa, mucin depletion and plasmacytosis

Management (Crohn’s disease)

There are two focuses of treatment for IBD – inducing remission to control acute flares of symptoms and then maintaining remission by continuing treatment to establish good symptom control.

Assessment of severity

When a patient with Crohn’s disease presents with new or worsening symptoms, it is important to assess the severity, in order to guide management.
One method used to help determine this is the Crohn’s Disease Activity Index (CDAI), which can be found in the table below.

Table 2: Crohn’s Disease Activity Index (CDAI). See References.

Interpretation:

CDAI < 150 = clinical remission

CDAI 150-220 = mild Crohn’s disease

CDAI 220-450 = moderate to severe Crohn’s disease

CDAI > 450 = severe-fulminant disease

Mild-moderate disease

Inducing remission

The treatments differ for ileal and proximal disease, or diffuse colitis/disease involving the left colon. Budesonide is used as the first line for proximal disease, with prednisolone as an alternative.

Prednisolone is instead the first line for diffuse/left colonic disease, with aminosalicylates (5-ASAs) agents such as sulfasalazine considered as an alternative.

Maintenance

If steroids have successfully induced remission, then these should be tapered down, with a follow up colonoscopy in six to twelve months for monitoring.

For those treated with 5-ASA agents, these are recommended to be continued as long term maintenance, with a follow up colonoscopy.

Moderate-severe disease

Inducing remission

Corticosteroids still play an important role in short term induction and provide rapid symptom relief.

Patients with high risk features such as stricturating or perianal fistulating disease may warrant early consideration of biologics.

First line biologics can include anti-TNF agents such as infliximab, which may be given with an immunomodulator, e.g. 6-mercaptopurine (6-MP), azathioprine or methotrexate (TPMT genotype testing is recommended prior to commencement of therapy with azathioprine or 6-MP.)

Alternative first line biologics include ustekinumab, an anti-IL-12/23 monoclonal antibody, which is indicated for patients who are biologic naive or refractory to standard therapy such as glucocorticoids, immunosuppressive agents, or anti-TNF agents. Vedolizumab is an anti-alpha-4-beta-7 (α4β7) integrin, and can be used for patients over the age of 60 or patients with a history of malignancy or infectious complications. Natalizumab is a humanised monoclonal antibody directed against alpha-4 integrin, but has limited use due to the potential for serious adverse events with particular concern for progressive multifocal leukoencephalopathy (PML).

Maintenance 

Immunomodulator therapy is a mainstay of maintenance therapy. This includes thiopurine therapy, Methotrexate and Mesalazine. There is also a role for anti-TNF, such as Infliximab and Adalimumab. Other biologic therapies include Vedolizumab, Ustekinumab

Severe-fulminant disease

Severe-fulminant Crohn’s disease is considered when symptoms are refractory to conventional therapy, or when complications such as intestinal obstruction, peritonitis or intra-abdominal abscess arise. Hospitalisation should be urgently arranged with prompt abdominal imaging and surgical consultation, if indicated.

In the context of an intraabdominal abscess, intravenous antibiotics, along with surgical or radiologically guided drainage, will be required.

If refractory to corticosteroid therapy or maintenance immunomodulatory therapy, biologic agents are considered.

Surgical management of Crohn’s disease

Failure to respond to medical treatment, severe acute disease, or complications may require surgical intervention – with key indications summarised below.

• Persistent inflammation causing intractable symptoms – may require surgical resection
• Bowel perforation
• Enteric fistula
• Intra-abdominal, retroperitoneal or abdominal wall abscesses – may require percutaneous or surgical drainage, with surgical excision of affected bowel segment
• Bowel obstruction – likely secondary to fibrosis or strictures, can be managed with endoscopic dilation, strictureplasty or surgical resection
• Enteric fistula refractory to medical management
• Small or large bowel cancer secondary to Crohn’s disease – requiring surgical excision or resection

Management (ulcerative colitis)

Assessment of severity

Tools used to assess the severity of acute ulcerative colitis include the Truelove and Witts severity index.

Table 3: Truelove and Witts severity index. See References

The severity of disease can also be measured by the extent of the disease, i.e. how far throughout the colon the inflammation has spread.

• Ulcerative proctitis = disease within 18cm of the anal verge and distal to the rectosigmoid junction
• Ulcerative proctosigmoiditis = disease limited to the rectum and sigmoid colon with no involvement of the descending colon
• Left-sided colitis = disease present beyond the sigmoid colon and extending as far as the splenic flexure
• Extensive colitis = continuous inflammation that starts at the rectum and extends beyond the splenic flexure

Mild-moderate disease

Induction of remission 

Topical mesalamine (suppository of enema) is used as the first line for proctitis or proctosigmoiditis, with topical steroids or oral 5-ASA agents as alternatives.

Left-sided or extensive colitis is treated with combination oral and rectal 5-ASA agents. Topical or oral steroids can be added if disease does not initially respond.

Maintenance

For proctitis or proctosigmoiditis, topical mesalamine is also first line, and oral 5-ASA is used if these drugs were required to induce remission.

For left-sided or extensive colitis, topical mesalamine is generally effective for maintenance therapy.

Moderate-severe disease

Induction of remission

Remission can be induced with anti-TNF therapy with or without immunomodulators. Systemic glucocorticoids (intravenous or oral) can be used but should be avoided as part of long-term therapy due to the extensive side effect profile. Failure of a clinical and biochemical response after 3 days of intravenous steroid therapy should prompt an assessment regarding medical rescue therapy or surgical management.

Medical rescue therapy can be administered with either ciclosporin or infliximab. Contraindications to ciclosporin therapy include abnormal renal function, uncontrolled hypertension, uncontrolled infections, malignancy, low serum magnesium, and failure to comply with dosing/monitoring. Contraindications to infliximab include active uncontrolled infection, latent (untreated) TB, demyelinating disease, heart failure, and malignancy.

Maintenance

Maintenance therapy depends on the initial agent required for remission. For example, if an anti-TNF was used to induce remission, then this can be continued. There should be an aim to withdraw immunomodulator therapy based on response to biologic therapy. If glucocorticoids were used for induction, then a thiopurine may be used for maintenance therapy.

Fulminant ulcerative colitis

Typically managed in critical care – treatment is similar to that of acute severe ulcerative colitis, but with more intensive monitoring and the potential for organ support.

Surgical management of ulcerative colitis

May be indicated for patients with acute severe disease, which is refractory to systemic steroids and immunosuppressants. Interventions include total abdominal colectomy with end ileostomy.

Complications such as bowel perforation or toxic megacolon (see below) also necessitate surgical intervention.