Inflammatory Bowel Disease
Transcript of Inflammatory Bowel Disease
PRESENTED BY
B.Avanthi.
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
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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
fistulasCommon Absent
Abdominal pain Uncommon Common
Fever , Malaise Uncommon Common
Bloody Diarrheoa Frequent Occasional
Location Only colon GIT
Anatomic distributionContinuous, begins
distallySkip lesions
Weight loss Occasional FrequentComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER,
pHARMACOTHERAPY a pathophysiologic appraoch josepht. dipiro18
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,
hypoalbuminaemia
Common 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 AbsentComprEhensive 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
ComprEhensive pharmacy review –LEON shargel, practical medicine- alagappan38
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
ComprEhensive pharmacy review –LEON shargel, practical medicine- alagappan39
BARIUM ENEMA
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COMB SIGN
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COBBLE STONE SIGN
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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
ComprEhensive pharmacy review –LEON shargel44
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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 colitisGradual 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
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Moderate ulcerative colitisMore severe diarrhoea with frequent bleeding
Abdominal pain & tenderness but not severe
Mild fever , anemia & hypoalbuminemia,
tachycardia.
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Severe ulcerative colitisSevere 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
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Classification of CROHN’s disease
ComprEhensive pharmacy review –LEON shargel52
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ComprEhensive pharmacy review –LEON shargel54
TREATMENTGoals of therapy
Induce and maintain remission.
Ameliorate symptoms
Improve patients quality of life
Adequate nutrition
Prevent complication of both the disease and
medications
ComprEhensive pharmacy review –LEON shargel55
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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
ComprEhensive pharmacy review –LEON shargel59
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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AMINOSALICYLATESSULFASALAZINE(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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STEROIDSHYDROCORTISONE (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
RANG AND DALE pharmacology review, adverse drug reactions-grover63
Biologic agents: anti-tnfADALIMUMAB (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.,.
RANG AND DALE pharmacology review, adverse drug reactions-grover64
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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