Inflammatory Bowel Disease

PRESENTED BYB.Avanthi.

PHARM.D IV YEAR,11421T0003.

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OVERVIEWDefinition

Epidemiology

Etiology

Pathophysiology

Clinical presentations

Extra intestinal manifestations

Complications

Investigations

Classification

Treatment

Prevention

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Inflammatory Bowel Disease (IBD) is commonly used to

describe 2 idiopathic diseases of GIT with closely related

presentations, these diseases are ULCERATIVE

COLITIS(UC) and CROHN’S DISEASE(CD)

Ulcerative colitis is a Chronic inflammation condition of

GIT mucosa and is primarily found in rectum and colon

where as Crohn’s Disease is a transmural inflammation

of GI mucosa and can be found throughout the GIT from

mouth to the anus and normally CD affects the small

bowel and colon

COMPREHENSIVE PHRARMACY REVIEW ,7TH EDITION , P g.no 1143

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IBD- Inflammatory Bowel Disease

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Epidemiology Ulcerative colitis

Age:15-40 yrs (Young adults)

Sex: No variation between men and women or

between socioeconomic group

High incidence areas: USA and northern-western

Europe

Clinical medicine, kumar and clarks

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contd..

CROHN’s disease

Age:1st peak 15-30 years of age, 2nd peak around 60

years

Sex Marginally more common in females

High incidence areas: North America, UK,northern

Europe

Clinical medicine, kumar and clarks

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etiology• DIET:

• Fat intake

• Fast food ingestion

• Milk and fibre consumption

• Total protein and energy intake

• DRUGS:

• NSAIDS: DICLOFENAC

• Antibiotics: may precipitate the relapse

• Oral contraceptives increase the risk of developing CD

• Smoking is protective against UC but increases the riskof CD

Clinical pharmacy and therapeutics, roger walker and cate whittlesea7

CONTD..GENETICS:

• If a patient has IBD, the lifetime risk that a first-degree relative will be affected is ~15%.

• If two parents have IBD, each child has a 36% chance of being affected.

• In twin studies , 58% of monozygotic twins are concordant for CD and 6% are concordant for UC, whereas 4% of dizygotic twins are concordant for CDand none are concordant for UC.

• Mutations of gene CARD15/NOD2 on chromosome 16 is associated with SI CD 2 other genes – OCTN1, DLG5

ETHNIC: Jews are more prone to IBD than non jews.

STRESS: Increase the relapse of IBD

Clinical pharmacy and therapeutics, roger walker and cate whittlesea8

CONTD..

INFECTION:

Mycobacterium paratuberculosis : CD

Diarrhoea :Ulcerative colitis

Clinical pharmacy and therapeutics, roger walker and cate whittlesea

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PATHOPHYSIOLOGY

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Davidson’s principle and practice of medicine12

Bacterial antigens are taken up by specialized M cells, passbetween leaky epithelial cells or enter the lamina propriathrough ulcerated mucosa

After processing they are presented on type 1 T-helper cells byantigen presenting cells (APC) in the lamina propria.

T-cell activation and differentiation results in Th1 T cellmediated cytokine response

With the secretion of cytokines including gamma interferon(IFNƴ)

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Further amplification of T cells perpetuates the inflammatoryprocess with activation of non immune cells and release of theimportant cytokines.

Eg: IL-12, IL-23, IL-1, IL-6 and tumor necrosis factor (TNF)

These pathways occur in all normal individual exposed toinflammatory insults and this is self limiting in healthy subjects

In genetically predisposed persons, dysregulation of innateimmunity may trigger inflammatory bowel disease.

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CLINICAL PRESENTATION OF IBD

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DISTINGUISHING CHARACTERISTICS OF CROHN’s disease AND Ulcerative colitis

Characteristic Feature Ulcerative Colitis Crohn’s Disease

Abdominal tenderness May be present Common

Abdominal wall and internal fistulas Common Absent

Abdominal pain Uncommon Common

Fever , Malaise Uncommon Common

Bloody Diarrheoa Frequent Occasional

Location Only colon GIT

Anatomic distribution Continuous, begins distally Skip lesions

Weight loss Occasional Frequent

ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologic appraoch josepht. dipiro

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Characteristic Feature Ulcerative colitis Crohn’s disease

Palpable mass Rare Common

Intra-abdominal abscess Rare Common

Bowel Obstruction Rare Common

Antibiotic response Rare Frequent

Skip lesions Rare Frequent

Effect of smoking Often improves Often worsens

Serologic markers

ASCA +

P-ANCA +

15%

70%

65%

20%

Iron deficiency anaemia, raised

CPR/ ESR, hypoalbuminaemiaCommon Common

Recto vaginal fistula Rare Frequent

Perianal Fistula Rare Frequent

ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologic appraoch josepht. dipiro 19

PATHOLOGIC FEATURES OF CD AND UCCharacteristic feature Crohn’s disease Ulcerative colitis

Transmural Inflammation Common Uncommon

Granulomas Common Rare

Fissures Common Rare

Fibrosis Common No

Sub mucosal inflammation Common Uncommon

Rectal involvement Rare Common

Ileal involvement Very Common Rare

Strictures Common Rare

Crypt abcess Rare Very common

Linear clefts Common Rare

Cobblestone appearance Common Absent

ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologicappraoch josepht. dipiro

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RADIOLOGIC features of ibd

Crohn’s disease Ulcerative colitis

Nodularity

GranularityCollar button ulcers

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EXTRAINTESTINAL MANIFESTATIONS OF IBD

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stomatitis

Aphthous ulcers

MANIFESTATIONS OF IBD

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UVEITIS

EPISCLERITIS27

Cobblestone appearance

NEPHROLITIASIS

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Pyoderma grangenosum

ERYTHEMA NODOSUM

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SPONDYLITIS

OSTEOPOROSIS30

COMPLICATIONS OF IBD

COMPLICATIOS

Bleedings

Stricture

FistulaToxic

megacolon

Cancer

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INVESTIGATIONS

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INVESTIGATIONS

Endoscopy

Colonoscopy

Histopathology

Radiology

Hematological test

Microbiological stool

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INVESTIGATIONSCrohn’s disease Ulcerative colitis

Blood Test

•CP with morphology: Normocyticnormocromic anemia of CROHNic disease•Serum B12 level may be low.•Raised ESR, CRP and raised WBC count.•Hypo albuminaemia.•Blood culture in septicaemia.

•Fe deficiency anemia•Raised white cell and platelet count•Raised ESR, CRP•Hypo albuminaemia

Serological Test

• Saccharomyces cerevisiae antibody is usually present•P-ANCA negative

•P-ANCA may be positive

Stool culture

•Should always be performed in both to rule out infective cause

ComprEhensive pharmacy review –LEON shargel, practical medicine- alagappan37

CONTD..Crohn’s Disease Ulcerative Colitis

Radiography

Plain ABD. X-ray:•Loss of haustral markings and shortening of bowel Is seen in sever lession.

•Narrowing of bowel lumen is seen

Ultrasound:•Thickened small bowel loops and mesentery or abscess

•Thickening of colonic wall and presence of free fluid in abdominal cavity

Barium Enema (contraindicated in toxic megacolon)•Skip lesions•Rose thorn appearance•String appearance•Cobble stone appearance•Omega sign are also seen

•Ulcerations•Pseudopolyps•Loss of haustration•Shortening of bowel is seen


CONTD..Crohns disease Ulcerative colitis

Instant Barium enema•Patchy sup. Ulceration to wide spread deep•Cobble stone appearance and narrowing

•Superficial ulcers •Shortened and narrowed colon in long standing disease

Colonoscopy•Fissures and fistulae •Pseudopolyps

•Mucosal granularity and hyperemia

High resolution USG. And spiral CT•Radionuclide scan with gallium labeled polymorphs or indium or technetium labeled leucocytes •Capsule imaging of the gut.

•Radionuclide scan used to assess colonic inflammation

Stricture evaluation and dilationcomplicated Lesser complicated


BARIUM ENEMA

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COMB SIGN

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COBBLE STONE SIGN

CLASSIFICATION OF ulcerative colitis and CROHN’s disease

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Anatomical classification of ulcerative colitis and CROHN’s disease

ULCERATIVE COLITIS CROHNS DISEASE

Proctitis

Proctosigmoiditis

Left sided colitis

Pancolitis

Backwash ileitis

Gastro duodenal Crohn’s

disease( gastroduodenitis)

Jejunoileitis

Ileitis

Ileocolitis

Crohn’s (granulomatous)

colitis

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a.Gastroduodenal Crohn’s disease

( gastroduodenitis)

b.Jejunoileitis

c.Ileitis

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d. Ileocolitis

e.Crohn’s(granulomatous) colitis

truelove and witts criteria for assessing severity of ulcerative colitis

FEATURE Mild Moderate Severe

Stool frequency per

day

<4 4-6 >6 (mostly bloody)

Pulse (beats/min) Normal Intermediate >90bpm

Rectal bleeding Little Moderate Large amounts

Heamoglobin Normal Intermeidiate <10.5g/ dL

Weight Loss (%) None 1-10 >10

Temperature Apyrexial Intermediate 38.8 0C on 2 of 4 days

ESR <20 mm/h 20-30 mm/h >30mm/h

Albumin (g/dl) Normal 3-3.5 <3

Clinical pharmacy and therapeutics– roger walker48

Mild ulcerative colitis Gradual onset

Infrequent diarrhoea (<4movements/day)

Intermittent rectal bleeding

Stool may be formed or too loose in consistency

Fecal urgency ,tenesmus,left lower quadrant pain

relieved by defecation

NO significant abdominal tenderness


Moderate ulcerative colitis More severe diarrhoea with frequent bleeding

Abdominal pain & tenderness but not severe

Mild fever , anemia & hypoalbuminemia,

tachycardia.


Severe ulcerative colitis Severe diarrhoea with >6-10 bloody bowel

movements per day

Severe anemia , hypovolemia ,imparied nutrition &

hypoalbuminemi,ELEVATED esr

Abdominal pain & tenderness

FULMINANT COLITIS:

Subset of severe disease with rapidly worsening

symptoms & signs of toxicity


Classification of CROHN’s disease


TREATMENT Goals of therapy

Induce and maintain remission.

Ameliorate symptoms

Improve patients quality of life

Adequate nutrition

Prevent complication of both the disease and

medications


NON PHARMACOLOGICAL THERAPY

Nutrition and Diet Support :

Patients with moderate to severe IBD are often malnourished.

The nutritional needs of the majority of patients can be

adequately addressed with enteral supplementation. Patients who

have severe disease may require a course of parenteral nutrition.

Probiotic formulas have been effective in maintaining remission

in ulcerativecolitis.

Supplemental fat soluble vitamins,medium supplemental

triglycerides and parenteral vitamin B12

Avoid high fibre diet in presence of diarrhoea and dysentry.

Pathology and therapeutics for pharmacists-GREEN AND HARRIS,practical medicine-alagappan57

Surgery:

• For ulcerative colitis, colectomy may be performed whenthe patient has disease uncontrolled by maximummedical therapy or when there are complications of thedisease such as colonic perforation, toxic dilatation(megacolon), uncontrolled colonic hemorrhage, or colonicstrictures.

• The indications for surgery with Crohn’s disease are notas well established as they are for ulcerative colitis, andsurgery is usually reserved for the complications of thedisease. There is a high recurrence rate of Crohn’sdisease after surgery.

Pathology and therapeutics for pharmacists-GREEN AND HARRIS,practical medicine-alagappan58

Pharmacological therapy of ibdAgents used in IBD

• AMINOSALICYLATES

• STEROIDS

• AZATHIOPRINE & 6-MERCAPTOPURINE

• METHOTREXATE

• CYCLOSPORINE & TACROLIMUS

• BIOLOGIC AGENTS• ANTI TUMOUR NECROSIS FACTOR THERAPY

• ANTIBIOTICS• METONIDAZOLE AND CIPROFLOXACIN

• RIFAXIMIN

• PROBIOTIC AND PREBIOTIC THERAPY

• ANTI SPASMODICS AND ANTI DIARRHEALS

• ANTIDPRESSANTS AND ANXIOLYTICS

• ANALGESICS

SURGERY


Management of ibdAgents used in IBD

• AMINOSALICYLATES• STEROIDS• AZATHIOPRINE & 6-MERCAPTOPURINE• METHOTREXATE• CYCLOSPORINE & TACROLIMUS• BIOLOGIC AGENTS

• ANTI TUMOUR NECROSIS FACTOR THERAPY

• ANTIBIOTICS• METONIDAZOLE AND CIPROFLOXACIN• RIFAXIMIN

• PROBIOTIC AND PREBIOTIC THERAPY• ANTI SPASMODICS AND ANTI DIARRHEALS• ANTIDPRESSANTS AND ANXIOLYTICS• ANALGESICSSURGERY

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AMINOSALICYLATES SULFASALAZINE(Salazar,Salazopyrin)

MESALAZINE( Coolgut,Cosacol)

OLSALAZINE(Dipentum)

BALSALAZINE(Balacol, Colorex)

MECHANISM OF ACTION: Salicylic acid moiety released is absorbed and has anti-inflammatory action.

ADVERSE EFFECTS:

Nausea and vomiting

Headache

Rashes

Rarely bone marrow dyscrasias,

Liver dysfunction.RANG AND DALE pharmacology review, adverse drug reactions-grover

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STEROIDS HYDROCORTISONE (Ciplorin,Labocort)

PREDNISONE(Deltasone, Rayos)

BUDESONIDE(Buovent,Derinide)

METHYL PREDNISONE(Alred,Biolone)

MECHANISM OF ACTION :

ADVERSE EFFECTS:

Suppression of response to infection

Growth suppression in children

Osteoporosis

Iatrogenic cushing’s syndrome

RANG AND DALE pharmacology review, adverse drug reactions-grover62

IMMUNUSUPPRESANTS

AZATHIOPRINE(Azap)

CYCLOSPORINE(Graftin,Imusporin)

MERCAPTOPURINE(Empurine,6MP)

METHOTREXATE(Imutrex,Caditrex)

ADVERSE EFFECTS:

Leukopenia,

macrocytic anemia

Thrombocytopenia

alopecia ,

steatorrhea

hepatotoxicity

MECHANISM OF ACTION


Biologic agents: anti-tnf ADALIMUMAB (Humira)

INFLIXIMAB (Remicade)

CETUXIMAB(Erbitux)

NATALIZUMAB(Tysabri)

ETANERCEPT(Enbrel,Enbrol)

MOA: It is a monoclonal antibody against TNF-alpha that binds with TNF-alpha and prevents its interaction with cell surface receptors in inflammatory cells.

ADVERSE EFFECTS:

Upper respiratory tract infections with cough

Nausea and vomiting, reactivation of latent TB AND Hepatitis B etc.,.


antibiotics

• METRONIDAZOLE(Metrogyl)

• CIPROFLOXACIN (Ciptec,Ciproxin)

• RIFAXIMIN(Rcifax,Xifaxan)

ADVERSE EFFECTS:

GIT disturbances

Anorexia

Occasionally can cause Dizziness

Myalgia

Ataxia

Hepatitis

Blood dyscrasias

RANG AND DALE pharmacology review,adverse drug reactions-grover65

Treatment algorithm for CROHN’S DISEASE

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Pathology and therapeutics for pharmacists-GREEN AND HARRIS 67

Treatment algorithm for Ulcerative colitis

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Pathology and therapeutics for pharmacists-GREEN AND HARRIS69

Novel agents currently under investigation for treating inflammatory bowel disease

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PREVENTION OF IBD

Stop smoking

Do regular exercise

Healthy diet

Do not use NSAIDs without doctor’s advice

Do not use ANTIBIOTICS unless they have been

prescribed for you by a doctor

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Inflammatory Bowel Disease

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