Inflammatory bowel disease - Standard Treatment Guidelines

Inflammatory bowel disease (IBD) represents a group of idiopathic chronic inflammatory intestinal conditions. The two main disease categories included are Crohn’s disease (CD) and ulcerative colitis (UC), with both overlapping and distinct clinical and pathological features. In addition the spectrum also comprises two categories ; IBD unclassified and indeterminate colitis. The pathogenesis of IBD is still under investigation. The most simplified view is that intestinal injury results due to aberrant immune response to commensal bacteria in a background of genetic predisposition.

Ministry of Health and Family Welfare has come out with the Standard Treatment Guidelines for Inflammatory bowel disease. Following are its major recommendations.

Case definition:

• Ulcerative colitis: Ulcerative colitis is a chronic disorder of unknown etiology in which a part or the whole of the mucosa of the colon becomes diffusely inflamed and ulcerated. Rectum is involved in a vast majority of the cases.


• Crohn’s Disease: A chronic granulomatous disease which can affect any part of GI tract in a discontinuous, asymmetric manner. Unlike Ulcerative colitis which is a mucosal disease, Crohn’s disease is a transmural disease.


• IBD unclassified: Categorization is not possible after clinical, radiological, endoscopic and histological features


• Indeterminate colitis: Categorization is not possible even after evaluation of resected specimen.

Incidence of The Condition In Our Country

The epidemiological studies from this region are being made available it is clear that the incidence and prevalence rates of IBD in Asia–Pacific region are low compared with Europe and North America. They are however, increasing rapidly.

There are substantial variations in the incidence and prevalence rates of IBD in various ethnic groups in Asia. The highest incidence rates are recorded from India, Japan and the Middle East and there exists a genetic predisposition of South Asians (Indians, Pakistanis and Bangladeshis) to ulcerative colitis (UC). In a study done in 2001 from Ludhiana in Punjab, the crude prevalence rate was 44.3/105 . The incidence was calculated after a second visit to the same area one year later. The crude incidence rate was 6.02/105 . The incidence rate of UC in India is higher than in Asian countries like Japan (1.95/105 ) and Korea (1.23/105 ). There is no population-based study on Crohn’s disease (CD) in India, however, the accepted perception is that the incidence of CD is rapidly rising in India. The peak age of incidence of CD is the third decade of life, with a decreasing incidence rate with age. The incidence rate in UC is quite stable between the third and seventh decades.

Differential Diagnosis

The main differential diagnosis of Ulcerative colitis and Crohn’s disease are :

Ulcerative colitis	Crohn’s disease
Acute self limiting colitis	Intestinal Tuberculosis
Amoebic colitis	Acute self limiting colitis
Crohn’s Disease	Amoebic colitis
HIV enteropathy	Ulcerative colitis
	Behcet’s disease
	NSAID enteropathy
	HIV enteropathy

Prevention And Counselling

IBD is an autoimmune disease, and environmental factors which can trigger an episode have not been identified, hence primary prevention strategy is not possible. There is a family history in 5% of IBD patients.

Optimal Diagnostic Criteria, Investigation, Treatment & Referral Criteria

*Situation 1: At Secondary Hospital/ Non-Metro situation: Optimal Standards of Treatment in Situations where technology and resources are limited

There is no gold standard test available to make a diagnosis of IBD. A diagnosis of ulcerative colitis or Crohn’s disease is made on the basis of compatible clinical history, examination, imaging, endoscopy and histology findings.

Clinical Diagnosis:

History

The most important features are the chronic duration of symptoms and the frequent remissions and relapses which characterize IBD and help in distinguishing from other infectious diseases affecting the large and small bowel.

Ulcerative colitis

1. Diarrhea : Large bowel diarrhea which is daytime or nocturnal

2. LGI bleed : Blood may be mixed with stool and at times separate from the stools

3. Rectal symptoms: tenesmus, urgency , frequency of stools

4. Abdominal pain and fever in case of severe disease

5. Symptoms are limited to large bowel

Crohn’s disease(CD)

Symptoms depend upon the site of involvement. In CD , any part of bowel from esophagus to anal canal may be involved .

Small Intestinal involvement / Ileocolonic involvement :

1. Abdominal Pain

2. Symptoms suggestive of recurrent partial intestinal obstruction may be present

3. Chronic diarrhea

4. Fever, anorexia, weight loss

Large bowel involvement :

1. Chronic diarrhea

2. Hematochezia

3. Peri anal disease

4. Fever, weight loss

5. Abdominal pain

Upper GI involvement

1. Dysphagia, odynophagia

2. Epigastric pain

3. Symptoms suggestive of gastric outlet obstruction

Extraintestinal manifestations (EIM) : Arthritis is the most common EIM and is observed in 15-20% of cases. Other extraintestinal complications include ankylosing spondylitis, pyodermagangrenosum, erythema nodosum, iritis, uveitis, episcleritis, and primary sclerosing cholangitis.

Complications include :

1. Hemorrhage: profuse bleeding from ulcers in UC. Bleeding is less common in CD. Massive bleeding in CD is more often seen from ileal ulceration than colitis.

2. Strictures, bowel perforation and Intra-abdominal abscesses in CD.

3. Fistulas and perianal disease in CD

4. Colorectal cancer: Significantly increased risk of colon cancer in UC after 8 years of diagnosis; the risk is lower in CD as compared to UC.

Investigations:

Primary and secondary care settings :

• Stool for ova and cysts


• Haemogram and Serum albumin


• Sigmoidoscopy (if available)


• Barium enema for ulcerative colitis


• In India, at present, a suspected case of Crohn’s disease should always be referred to a tertiary care hospital before initiating therapy. This is so as to rule out intestinal tuberculosis which closely mimics Crohn’s disease.

Referral Hospitals:

Stool examination:

i ) Parasites

ii)Clostridium difficile(should be considered even in absence of antecedent antibiotics).

Blood tests :

i) Haemoglobin, ESR , serum albumin , Human immunodeficiency virus (HIV)

ii) Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and antiSaccharomyces cerevisiae antibodies (ASCA): need not be done

iii) Celiac serology

• Monteux skin test


• Chest X ray


• Sigmoidoscopy / Colonoscopy An endoscopic examination is necessary

a) to establish the diagnosis

b) to assess severity of disease

c) to take targeted mucosal biopsies . In cases with severe activity, a full length colonoscopy is not indicated as there is a high risk of perforation.

Ulcerative colitis:

An ileocolonoscopy is indicated to establish the extent of disease

Crohn’s Disease: Endoscopic procedures required include : 1) ileocolonoscopy 2) UGI endoscopy ( especially in pediatric cases) 3)Capsule endoscopy/ double balloon enteroscopy if small bowel involvement suspected.

• Histology

Multiple mucosal biopsies should be taken from inflamed areas. Features suggestive of ulcerative colitis include crypt architectural destruction, crypt abscesses, goblet cell depletion, paneth cell metaplasia, basal plasmocytosis. In Crohn’s disease non caseating granulomas may be seen in 30% of cases

• Imaging

1. Abdominal X ray: In severe UC or CD where perforation or toxic mega colon is suspected. In CD, if intestinal obstruction is suspected.


2. Contrast enhanced computed tomography ( Enteroclysis/Enterography) : In cases with CD i) to evaluate small intestinal involvement ii) to differentiate from intestinal tuberculosis


3. Barium meal follow through: If facilities for CT (enteroclysis) are not present.

• These investigations not only help in diagnosing the disease but also help in determining the extent and severity of the disease . The tables below show the classification for extent and severity of UC and CD.

Table 1: Disease extent in Ulcerative colitis:

Extent	Disease	Description
E1	Ulcerative proctitis	Involvement limited to rectum
E2	Left sided UC (distal colitis)	Involvement distal to the splenic flexure
E3	Extensive UC (Pancolitis)	Involvement extends proximal to the splenic flexure

Table 2: Disease activity in Crohn’s Disease (ACG classification)

Mild ( corresponds to CDAI < 150)	Moderate ( corresponds to CDAI 150-220)	Severe ( corresponds to CDAI 150>450)
Ambulatory, eating <10% weight loss No features of Dehydration Obstruction, fever, Abdominal mass or Tenderness CRP > upper limit	Intermittent voming, Abdominal pain, > 10% Weight loss No feature of Dehydration Obstruction, fever, Abdominal mass or Tenderness CRP > upper limit	BMI < 18, cachexia, Dehydration Evidence of Obstruction or Abscess Persistent symtoms Despite intensive Rx

Table 3 : Montreal Classification of Crohn’s disease phenotype

Age	A1 : < 16 years A2 : 17-40 years A3 : > 40 years
Location	L1 : Ileal L2 : Colonic L3 : Isolated upper GI disease*
Behaviour	B1 : Non structuring non penetrating disease B2 : Structuring disease B3 : Penetrating disease P : perianal disease modifier #

In addition , these investigations also help in 1) differentiating Ulcerative colitis from Crohn’s disease 2) Intestinal tuberculosis from Crohn’s disease as shown in the tables below

Table 4 : Features for differentiating between ulcerative colitis (UC) and Crohn’s disease (CD) (adapted from World Gastroenterology Organisation Global Guidelines June 2009)

	Typical UC features	Typical UC features
Clinical	Frequent small-Volume diarrhea with urgency Predominantly bloody diarrhea	Diarrhea accompanied by abdominal pain and malnutrition Stomatitis Abdominal mass Perianal lesions
Endoscopic and radiological	Diffuse superficial colonic inflammation Involvement of rectum, but this can be patchy Shallow erosions and ulcers Spontaneous bleeding	Discontinuous transmural asymmetric lesions Mainly involving ileum and right sided colon Cobblestone appearance Longitudinal ulcer Deep fissures
Histopathological	Diffuse inflammation in mucosa or submucosa Crypt architecture distortion	Granulomatous inflammation Fissures or aphthous ulcers can be seen: often transmural inflammation

IBD management should be based on:

• UC vs. CD (although this is less important for early aspects of treatment)


• Disease location and phenotype


• Severity

The goals of treatment are to:

• Maintain steroid-free remissions (decreasing the frequency and severity of recurrences and reliance on steroids)


• Prevent complications hospitalization and surgery

Treatment include two phases

• Induction of remission


• Maintenance of remission

Ulcerative colitis :

Disease extent: Proctitis and Proctosigmoiditis

• Inducing Remission

Proctitis : 5ASA suppositories ; Optimal dose : 1gm/day

Proctosigmoiditis : 5ASA enemas : 2-4 gm/

If no response within 4 week

Use of topical glucocorticoids

If still no response :

Use of hydrocortisone rectal drip: 200mg/200ml/1-2 hrs

• Maintaining remission

Oral 5 ASA in a dose of 1600-2400 mg daily may be used with or without topical therapy

If disease extent is left sided colitis/pancolitis, then the treatment may be planned as in the table below:

A. For Induction of remission depending upon the severity of disease

Mild to Moderate:	Severe :	Fulminant :
SZA : 4-6 gm/day 5ASA : 4gm/day	Oral steroids	Hospitalization IV steroids Intensive Therapy Surgery
No clinical response: Perdnisolone : 40-60 mg/day	No response : Hospitalization IV steroids Intensive Therapy
Steroid tapering : Very gradual Over 3-4 months

B. For maintenance of remission : Use of 5 ASA alone or 5ASA and azathioprine in patients

who require frequent steroids

Management guidelines in Crohn’s Disease ( as in the table below)

Inflammatory CD ( B1 phenotype)	Mild to moderate	Induction regime SSZ : left colon Budesonide : ileocolon	Remission : Azathioprine Methotrexate
	Moderate with systemic Symptoms Severe Small bowel extensive disease	Induction regime Prednisolone IV Hydrocortisone	Remission : Azathioprine Methotrexate
	Introduction of Infliximab	Corticosteroid dependent Corticosteroid refractory 2 courses of steroids/year Risk factors for Top Down rx group	Remission : IFX + Azathioprine Not Methotrexate
Fistulizing Disease (B3 phenotype)	Perianal : Simple vs complex	Antibiotics, azathioprine Infliximab , Surgery
	Non perianal	Surgery
Stricturing Disease (B2 phenotype)		Steroids/balloon dilatation/surgery/? Infliximab

Referral criteria:

Criteria for surgery referral :

• Toxic megacolon


• Perforation peritonitis


• Severe bleed


• Refractory to medical therapy


• Stricturing Crohn’s disease

Standard Operating procedure

a. In Patient : Patients with severe disease not responding to oral steroids

b. Out Patient : Patients with mild to moderate disease or patients in remission on follow up

c. Day Care : Any patient requiring infliximab maintenance infusion

WHO DOES WHAT? and TIMELINES

a. Doctor: Diagnose and strategise therapy

b. Nurse : Assist in administering drugs

c. Technician : Assist in endoscopy and imaging investigations

Guidelines by The Ministry of Health and Family Welfare :

developed by Dr Vineet Ahuja Deptt of Gastroenterology, All India Institute of Medical Sciences, New Delhi