INFLAMMATORY BOWEL DISEASES- CROHNS DISEASE AND ULCERATIVE COLITIS

               

                                                  INFLAMMATORY BOWEL DISEASES

                                                                                                                                    ( By Dr.S.Uma Devi.M.D.)

Basic concepts and importance of IBD

·         IBD is  idiopathic,chronic ,relapsing Inflammatory disorder of unknown etiology involving GI tract

·         Often it is a dignostic challenge

·          Etiology and pathogenesis is not known

·         There are no specific clinical or lab features to establish the diagnosis

·         Diagnosis of Ulcerative colitis and Crohns relies heavily on pathological interpretation of biopsy material

·         But  histologically Crohns and ulcerative colitis have varieties of  characteristic  but nonspecific pathological features-this poses diagnostic problems

·         So histological material should be evaluated in conjunction with ,clinical lab,radiological and scopy findings

·         Clinically also exceptions occur to the classical  picture which leads to diagnostic confusion

(e.g.Left sided Ulcerative colitis,Upper GI involvement of UC rectal sparing in UC)

-these  exceptions should not be misinterpreted as evidence against diagnosis)

·         In 5% a definite diagnosis cannot be established(with overlapping features)

Most of these Indeterminate type go for fulminant colitis

·         Crohns disease and UC have increase risk for dysplasia and carcinoma.

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Types of inflammatory Bowel Disease

 Major 2 types of IBD are

·         I.Chrons disease(CD)

·         II..Ulcerative colitis(UC)

         Ulcerative colitis is limited to the colon

         Chrons disease can involve any segment of the GI tract from mouth to anus.

·          IIIrd type .Intermediate type

A type of IBD in which distinguishing between UC and CD is impossible

Accounts for 10–15% of patients with colitis

                        

 Pathogenesis

As the ulcer heals, fibrosis leads to adhesions ,obstruction and abcess formation

Obstructive lymphatic edema is  atypical picture.

Lymph adenopathy is common

Types of pathology and associated clinical picture.:

Stricturing disease/penetrating disease/inflammatory disease.

Patterns of Involvement

3 major patterns

1.disease of ileum and ceacum

2.Disease confined to small intestine

3.Disease confined to colon

Clinical picture of Crohns disease

Onset may be with one of the following presentation

1.Right iliac fossa pain resembling appendicitis

Etiology:  of IBD

Not known

 What is known is IBD  it is immunologically mediated

Multiple etiologies proposed

1.      Immune response and Inflammatory mediators  play a role

Cytokines  from macrophages bind to various receptors         

Cytokines produce autocrine,paracrine and endocrine effects

They differentiate lymphocytes into different kinds of T cells

The immune response leads to chronic inflammatory process and disrupts intestinal mucosa

Other inflammatory mediators involved- Tnf-alpha

2.Genetic predisposition is found

3.Triggering event not known,

Certain microorganism (as yet unidentified)

 or some antigen and auto immune process

Normally in intestinal mucosa,inflammatory cells are present to protect from harmful

  luminal agents

Assumption- is in IBD inappropriate activation of mucosal immune system occurs

Immune response becoming excessive lead to profound tissue damage.

There is failure of body to turn off the normal immune response

IBD is treated as if it is auto immune disease but there is no consenses of opinion

 Research on genetics

Possibly linked to genes on chromosomes16, 5 and 6.

Triggering genes-Card15,  NOD2 /Card15

These genes may be just permissive  (allowIBD to occur)not causative .

First degree relatives have increased risk

Other factors implicated in IBD

·          As mentioned already -activation of immune system with inflammation of acute and chronic nature.

What activates this  still not known.

·         Environmental factors implicated(food, enteric microbes)

·         Smoking linked to Crohns ,not to UC

·         Appedicectomy in early age-protective for crohns disease

·         Psychological factors

Epidemiology; Rare in India

Peek incidence is between age 15 and 35;but onset may occur in any age

Children may be affcted

Male to female ratio equal in both Crohns and UC

Common in jewish population

Mortality

Frequent cause of death in IBD –

1.primary disease

Malignancy

Thromboembolic manifestations

Crohn’s disease

Synonyms for Chron’s disease
Regional enteritis,Terminal ileitis,granulomatous ileocolitis

Recurring episodes of  inflammation of any part of the bowel from mouth to anus

Commonly found in ileum

Pathology

Transmural inflammation

All coats of ileum involved

Mucosa-ulcerated

Submucosa-fibrosed

Muscular coat also involved

Result- linear ulceration,stricture, microperforation,fistulae

Skip lesions  characteristic  throughout bowel

(Affected area discontinuous-interspersed with normal area)

Ileum involved           

Histology

Transmural inflammation

Granulomas

Fissures

fistula

Fig 3.Crohn disease of the colon; a deep fissure extending into the muscle wall, a second, shallow ulcer (on the upper right), and relative preservation of the intervening mucosa. Abundant lymphocyte aggregates are present, evident as dense blue patches of cells at the interface between mucosa and submucosa

Pathogenesis:

 As ulcer the heals Fibrosis leads to adhesions and obstruction,abscess formation

Obstructive lymphatic edema is a typical feature

Lymphadenopathy is common

Types of pathology and associated clinical pattern

Stricturing disease,penetrating disease or inflammatory disease

Pattern of Involvement

3 major patterns

1. Disease of ileum and cecum

2. Disease confined to small intestine

3. Disease confined to colon

          

Clinical picture of Crohns disease

Onset may be with one of following presentation

1.      Right iliac fossa pain resembling appendicitis

2.      Recurrent episodes of sub acute  small bowel obstruction

3.      Diarrhoea

4.      Fistula either internal to intestine or external to abdominal wall.

Symptoms

1 General

Loss of weight,fever,anemia,anorexia

2. Pain; Severe continuous or colicky pain in the right iliac fossa or the lower abdomen

3. Diarrhoea: common, steatorrhoea may be present

4,Fistulae—

1. internal between loops of intestine(therby aggrevating or precipitating diarrhea)

.or between bowel and bladder(with frequency of micturition,dysurea,pneumaturia)

2.External-usually follows surgical intervention.

 Signs

 General:signs

 Fever,anemia,raised ESR

 Late stages-

cachexia,can be also iotrogenic  from  extensive resection or bypass procedures.

Abdominal signs

Distended

Palpable inflammatory mass often in rt iliac fossa

Signs of obstruction like abdominal distension,visible peristalsis,/ visible distended loops of small intestine

Course
Periods of active disease alternate with periods of remission     

Complications

Stricutre

Fistula

Anemia(from bleeding ulcers)

Infections

Compare Crohn’s disease and ulcerative colitis

Fig4.Comparison of the distribution patterns of Crohn disease and

ulcerative colitis, as well as the different conformations of the ulcers

 and wall thickenings

Investigations

1.Sigmoidoscopy/coloscopy

2Upper GI and small bowel series

Shows nodularity,rigidity

Ulcers –deep  and longtitudinal

Cobble stoning ,skip areas

Stricures,fistula

Small intestinal.distended loops,

.String sign- along narrow length of the bowel lumen is narrowed-usually in terminal ileum

(Refer fig 4).

           ULCERATIVE COLITIS                   

Similarities between Crohns disease and Ulcerative colitis

Certain aspects of treatment are common

Certain extra intestinal manifestations are common

Waxing and waning clinical course in both.(flare and remissions)

Note: Sometimes degree of inflammation need not correlate with severity of symptoms

So before medication, ascertain degree of disease activity objectively

Pathology:                                                      

Early stage-congestion and edema of mucosa

Histology

1.Inflammatory cell infiltrates with classical crypt abscesses

2. Next –Ulceration irregular

Edges of ulcer s infiltrated,not undermined

The intervening mucosa is inflamed(NO Skip lesions)

3.Eventually diffuse fibrosis of submucosa occurs

This converts the colon intonarrow fibrous tube.

4.Rectum is almost always involved.

Clinical features

Varies in

Severity

Course

And site of involvement

Classical type

Symptoms

Rectal bleeding

Diarrhea

Tenesmus

Abdominal pain fever, anorexia , and weight loss.

Site of involvement

1. Starts in

Recto sigmoid region and

 extends to other parts of the large intestine.

2. Localised  

At times it may remain localized to rectum or recto sigmoid

3.Other parts of colon

May start in other parts of colon and spread or remain localized

4 In some –retrograde ileal involvement occurs (Backlash ileitis)

Duration of attack

4-18 wks

Usually –remissions and exacerbations

Remission –lasts from 1-5 yrs

 Conditions precipitating remissions

Emotional tension,URI or other infections,surgery,antibiotics,cathartics

And dietary indiscretion

Clinical  varieties

1.Recurrent type

2.Continuous type

3.Single attack

4. Acute fulminant type

Complications

Severe anemia

Perianal abscess

Perforation of colon

Peritonitis

Toxic megacolon

Stricture formsation

Polyposis

·         Cancer risk

Related to extent of lesion and duration of colitis preceding

Dysplasia detected by surveillance colonoscopic biopsies

Complications due to chronic diarrhoea

Anemia –due to loss of blood and mucus

Hypoprotenemia

Wight loss

Gross vitamin deficiency

Hypokalemia –loss of K in stools

 Plus Extra intestinal manifestation mentioned below

Toxic megacolon. Complete cessation of colon neuromuscular activity has led to massive dilatation of the colon and black-green discoloration signifying gangrene and impending rupture

 Common differential diagnosis

Acute/chronic amebiasis,acute bacillary dysentry

Investigations

·         Sigmoidoscopy or colonoscopy

  Shows –mucosal erythema,granularity,friability,exudates,hemorrhage,ulcers

Pseudo polyps (regenerating mucosa)

·         Barium enema

Shows-loss of haustrations,mucosal irregularity,ulcerations
Ulcerative colitis. Ulcerated hemorrhagic

 surface with knobby pseudopolyps

• Xray

·         Ultra sound

·         MRI scan

·          

Other differential diagnosis for ulcerative colitis

1.Infectious enterocolitis-Typhoid,tuberculosis,amoebic and others

2.Others. Ischemic bowel disease,diverticulitis,radiation enterocolitis,

3Bleeding colonic lesions(e.g.Neoplasms) irritable bowel syndrome(no bleeding)

Fig6.Ulcerative colitis. Low-power micrograph showing marked chronic inflammation of the mucosa with atrophy of colonic glands, moderate submucosal fibrosis, and a normal muscle wall

Fig7.Ulcerative colitis. Microscopic view of the mucosa, showing diffuse active inflammation with crypt abscess and glandular architectural distortion

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Extra intestinal manifestations of  IBD (UC and CD)               

1.Joint: Peripheral arthritis-parallels activity of bowel disease,ankylosing spondylitis,and sacroilitis(activity independent of bowel disease)

2.Skin-Erythema nodosum,aphthous ulcers,pyodermagangrenosum,cutaneous crohns disease

3.Eye: Episcleritis,iritis,uveitis

4.Liver: Fatty liver,pericholangitis(intra hepatic sclerosing cholangitis,)cholangio carcinoma,chronic hepatitis

5.Others:Auto immune hemolytic anemia,phlebitis,pulmonary embolus

Investigations of ulcerative colitis-Details

1.Sigmoidoscopy

In acute stage

Mucosa – diffusely hyperemic.odematous,friable,superficially ulcerated

                Blood stained purulent discharge  on the surface

Sub acute stage-

Mucosa-granular.easily bleeds.edema masks normal vascular pattern

Healed stage or during remission

Mucosa may be normal (no granular appearance,no bleeding)

Close sigmoidoscopic DD

Acute bacillary dysentery differentiate by Swab or culture exam

2.Barium picture
1.May be normal but it does not rule out UC

2.Acute stage:

Loss of normal haustral pattern, ragged appearance decreased distesibility of colon and rectum

Chronic healed stage

Loss of normal haustral markings,smooth outline of bowel,decrease in lumen size nd length of bowel.Pseudo polypoid change in mucosa

Occasionally this picture may occur in normal descending and sigmoid colon.

Carcinomatous changes of rectum or sigmoid have to be looked into carefully with biopsy

 Common reasons for making a diagnosis of indeterminate colitis

Summary of the causes of unusual patterns of disease in Ulcerative colitis
1..treatment effect
                       2.low grade disease in remission
                 3.Appendiaceal involvement
                                                               4.Cecum /ascending colon inflammation inleft sided colitis
                            5.pediaric UC in (initial presentation
6.Back wash ileitis
          7.Rare UGI involvement
8.Fulminant colitis

TREATMENT OF IBD

                  There is no specific or curative treatment;Medical treatment is symptomatic.

                                                             

1.Rest in acute stages,hospitalization as  required   

2. Diet

Avoid high fiber diet in presence of diarrhea/dysentery

Avoid milk if sensitive to milk.

Nutritious diet prescribed

Supplement fat soluble vitamins,medium chain triglycerides,

Parenteral viatminB12.minerals

Eating smaller ,ore frequent meals

Very severe cases-nil oral,parenteral nutrion or defined enteral formulae

 This is effective inCD,but relapse  occurs fast when oral feeding is resumed

Advised in pre op preparation of malnourished patient

Drug should not replace drug therapy

Life style changes

Quitting smoking

Exercise

Stress reduction

Taking adequate rest

Supportive therapy                                                          

 Antidiarrheal agent in mild cases(loperamide)

Pain reliever-acetaminophen

Severe-IV hydration;Blood transfusion

DRUG THERAPY

Elimination of secondary infection

Antibiotic and chemotherapeutics

Metroniadazole

Ciprofloxacin

Try to avoid broad spectrum antibiotic –may induce diarrhea

For abscesses and skin infections

Metronidazole toxicity-peripheral neuropathy, ?carcinogenecity ,thrombophlebitis

Metronidazole  -effective in colonic CD requires 4-8 mths trial period

                         Dose 200mg qid

Antibiotics indicated also in toxic megacolon and severeUC

Aminosalicylates

Sulpha salazine

Mesalazine

Balsalazide

Olsalazine

Oral /rectal preparation

·         Sulfa salazine

Active component is 5Aminosalycilic acid(5-ASA)

Useful in  mild or moderate colonic disease  1gm oral qid                    

Useful for maintaining remission(only inUC)

May reduce risk of colorectal cancer

Side effects-hypersensitivity,pancreatitis,nausea,headache,

Caution in –pregnancy,breast feeding,renal impairement

(Toxicity  is due to sulfa pyridine component)

Idiosynchrosy-fever,rash,hepatitis,neutropenia

Alternative drug

·         Mesalazine  5ASA linked to other carriers

In slow release form or as enema

Gluco corticoids

Help in producing remission

Useful in severe case

Ileal or ileocecal CD

Prednisolone 40-60 mg od  and then taper

IV hydrocortisone 100 mg tid in hospitalized patient

IV ACTH  drip 120 U per day preferred in 1^st attack of UC

For  proctosigmoiditis nightly hydrocortisone retension enema.

 Toxicity –immunosuppression,pancreatitis ? carcinogenicity

Immuno suppressive agents       

Interefere with inflammatory pathway

Steriod sparing drugs or steroids not effective

Azathioprine 50-100 mg per day

6-mercaptopurine

Methotrxate if above 2 not effetive

Cyclosporin in active and chronic  disease

Must do periodic blood count and platelete count

Biological therapy

Infliximab

 It is Anti tnf-a monoclonal antibody

Infliximab prevents cytokines from binding to its receptors

Indication:severe activeCD intolerant to steroids or imuno suppresents

 Side effects-infusion rx,sepsis,activation of TB

Surgical therapy

 In crohns disease

Resection for

 fixed obstruction or stricturoplasty

abscesses

persistant symptomatic fistula

intractability

In Ulcerative colitis

Colectomy (curative for intractability)

Toxic mega colon if no improvement withwith aggressive medical therapyin 24-48 hrs

Cancer

Severe dysplasia

Ileal pouch anal anastamosis(IPAA)

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