ULCERATIVE COLITIS

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A CASE OF BLOODY DIARRHOEA : 

A CASE OF BLOODY DIARRHOEA PRESENTED BY: MAJ MUKESH KUMAR MODERATOR:LT COL DEBABRATA BANERJEE 1

Patient particulars : 

32 yrs old lady, homemaker Educated till 12th std R/o Ghazipur(eastern UP) Patient particulars 2

Presenting complaints : 

Bloody diarrhea × 20 days Presenting complaints 3

History of present illness : 

Bloody diarrhea : Frequency:10-12 per day Small volume Containing blood & mucus h/o passage of blood clots at the end of defecation sense of incomplete evacuation after defecation Assoc with heaviness in lower abdomen Assoc with nausea, easy fatiguability and gen weakness History of present illness 4

History of present illness : 

Bloody diarrhea : Not foul smelling No recognizable food particles History of present illness 5

History of present illness : 

Denies h/o: Fever Severe abdominal pain or distension Wt loss Travel in recent past Food indiscretion Drug/laxative ingestion History of present illness 6

History of present illness : 

No h/o: Oral ulcer Joint pain/backache Redness of eyes Subcutaneous nodules History of present illness 7

Slide 8: 

Past history Denies h/o similar illness No h/o TB No h/s/o Appendicitis Family history No h/s/o chronic bloody diarrhea in family members 8

Personal history : 

Consumes mixed diet No drug consumption, no addiction Denies high risk behavior Normal bowel and bladder habits prior to the illness 9 Personal history

Treatment history : 

Recd treatment at MI Room, NSG, Manesar to no relief Norfloxacin × 5 days Tinidazole Treatment history 10

Summary : 

32 years old lady presented with bloody large bowel diarrhea of acute onset with no constitutional symptoms Summary 11

Causes of bloody diarrhea.. : 

Causes of bloody diarrhea.. 12

INFECTIOUS CAUSES : 

INFECTIOUS CAUSES Bacterial infection Shigella spp Salmonella spp Campylobacter jejuni Clostridium difficile Yersinia enterocolitica Listeria monocytogenes Escherichia coli Aeromonas hydrophila Neisseria gonorrhoeae Chlamydia spp         . Viral infection Cytomegalovirus     Herpes simplex virus  Parasitic infestation Entamoeba histolytica  Schistosomiasis 13

NONINFECTIOUS CAUSES : 

NONINFECTIOUS CAUSES IBD: Ulcerative colitis Crohn's disease Collagenous colitis Lymphocytic colitis Drugs : NSAIDs Penicillamine Gold Chemotherapy Others : Radiation colitis Solitary rectal ulcer syndrome Ischemic colitis Graft-versus-host disease Diversion colitis Diverticulitis 14

General examination : 

Temp: 98℉ Pulse:94/min, reg BP: 106/70 mm Hg RAS Resp rate: 14/min Pallor+ No icterus, cyanosis, clubbing, edema or LNE No subcutaneous nodules, redness of eyes General examination 15

Systemic examination : 

ABDOMEN: Not distended Soft Liver/spleen not palpable No tenderness No ascites Bowel sounds normal Systemic examination 16

Systemic examination : 

CVS: S1S2 heard No murmur RESP: Trachea central No adventitious sounds heard Systemic examination 17

Systemic examination : 

CNS: HMF normal No neurological deficit MUSCULOSKELETAL SYSTEM: No swelling/tenderness of peripheral/axial joints Systemic examination 18

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INVESTIGATIONS 19

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20

Stool tests : 

Stool ME – no ova or cysts Stool culture – no Shigella, Salmonella Stool tests 21

Colonoscopy(done in civil) : 

Mucosa from rectum till mid transverse colon and beyond showing contiguous superficial ulcers starting from just beyond the anal verge extending proximally loss of vascular pattern and friability with pseudo polyp Imp: Extensive colitis ? IBD - UC ? Infective colitis 22 Colonoscopy(done in civil)

Slide 23: 

23 Ulcerative colitis

Slide 24: 

24 Endoscopic Image of Ulcerative Colitis with Pseudopolyps

Rectal mucosal biopsy : 

Focal areas of ulceration+ Crypt abscesses+ Cryptitis+ Architectural distortion+ Branching of glands+ Lamina propria shows increased lymphocytes and plasma cells No dysplasia/granuloma Rectal mucosal biopsy 25

Slide 26: 

Abdomen x-ray: no evidence of megacolon/gas under diaphragm Chest X-ray: normal Ultrasound Abdomen: normal 26

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27

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28

DIAGNOSIS : 

IBD - ULCERATIVE COLITIS 1st PRESENTATION SEVERE DISEASE EXTENSIVE COLITIS NO EXTRA INTESTINAL MANIFESTATION 29 DIAGNOSIS

Slide 30: 

Ulcerative colitis (UC): is a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granuloma on biopsy, affecting the rectum and a variable extent of the colon in continuity, which is characterized by a relapsing and remitting course. Colitis yet to be classified: is the term best suited for the minority of cases where a definitive distinction between UC, Crohn's disease, or other cause of colitis cannot be made after the history, endoscopic appearances, histopathology of multiple mucosal biopsies and appropriate radiology have been taken into account. Indeterminate colitis is a term preserved for pathologists to describe a Colectomy specimen which has overlapping features of ulcerative colitis and Crohn's disease. 30

Disease extent : 

Disease extent 31

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32

Mayo score : 

Mayo score 33

Endoscopic Severity (Baron׳s classification) : 

SCORE : 0 Normal mucosa 1 Loss of vascular pattern 2 Granular, nonfriable mucosa 3 Friability on rubbing 4 Spontaneous bleeding, ulceration 34 Endoscopic Severity (Baron׳s classification)

Slide 35: 

Remission -is defined as complete resolution of symptoms and endoscopic mucosal healing Response -is defined as clinical and endoscopic improvement -depends on the activity index used (for the purpose of clinical trials) 35

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Relapse -a flare of symptoms in a patient with established UC who is in clinical remission, either spontaneously or after medical treatment Early relapse -An arbitrary, but clinically relevant period of 3 months after achieving remission on previous therapy Pattern of relapse -Infrequent (≤1/yr) -Frequent (≥2 relapses/yr) -Continuous (persistent symptoms of active UC without a period of remission) 36

Slide 37: 

Steroid-refractory colitis -Patients who have active disease despite prednisolone up to 0.75 mg/kg/day over a period of 4 weeks Steroid-dependent colitis -Patients who are either i) unable to reduce steroids below the equivalent of prednisolone10 mg/day within 3 months of starting steroids, without recurrent active disease, or ii) who have a relapse within 3 months of stopping steroids 37

Slide 38: 

Immunomodulator-refractory colitis -Patients who have active disease or relapse in spite of thiopurines at an appropriate dose for at least 3 months (i.e.azathioprine 2–2.5mg/kg/day or mercaptopurine 0.75–1mg/kg/day in the absence of leucopenia) Refractory distal colitis -persistent symptoms due to colonic inflammation confined to the rectum (proctitis), or left side of the colon (more commonly the rectosigmoid colon), despite treatment with oral and topical steroids for 6–8 weeks 38

Extraintestinal manifestations : 

Cutaneous/Oral   Angular stomatitis  Aphthous stomatitis  Erythema nodosum  Oral ulcerations  Psoriasis  Pyoderma gangrenosum  Pyostomatitis vegetans  Sweet's syndrome (acute febrile neutrophilic dermatosis) Extraintestinal manifestations 39

Extraintestinal manifestations : 

Ophthalmologic   Conjunctivitis  Episcleritis  Scleritis  Uveitis, iritis Musculoskeletal   Ankylosing spondylitis  Peripheral arthropathy  Sacroiliitis Osteoporosis Extraintestinal manifestations 40

Extraintestinal manifestations : 

Hepatobiliary     Primary sclerosing cholangitis  Hepatic steatosis Hematologic     Autoimmune hemolytic anemia  Hypercoagulable state Extraintestinal manifestations 41

Apthous stomatitis : 

Apthous stomatitis

Pyoderma gangrenosum : 

Pyoderma gangrenosum

Erythema nodosum : 

Erythema nodosum

Specific complications of Ulcerative colitis.. : 

Specific complications of Ulcerative colitis.. Toxic megacolon Colonic Perforation Massive hemorrhage Dysplasia and colorectal cancer Stricture

Life-threatening complication : 

Life-threatening complication Toxic megacolon with Colonic perforation Fulminant illness, esp. on corticosteroid/ immunosuppressant Massive hemorrhage

Toxic Megacolon : 

Toxic Megacolon Incidence: 5~7% 50% patient present megacolon as their first ulcerative colitis attack Fever, tachycardia, leukocytosis, abdominal distention and tenderness Mortality:15~30%(decline in recent years), usually due to delayed surgery or MODS

Slide 48: 

48 Toxic megacolon

Perforation : 

Perforation Incidence:3~5% with megacolon existence 1% without megacolon Most common at Sigmoid colon Most common cause of death Corticosteroid can mask fatal peritonitis

Treatment options for achieving remission : 

Treatment options for achieving remission Mild disease: oral and rectal 5-ASA compounds Moderate disease: oral and topical 5-ASA compounds oral steroids azathioprine, 6-MP Severe disease: IV steroids Infliximab Cyclosporine Azathioprine, 6-MP Colectomy

Slide 51: 

51 Treatment for mild to moderate active disease

Slide 52: 

52 management of severely active ulcerative colitis

Treatment Day 01-07: : 

NPO IV FLUIDS IV HYDROCORTISONE 100 MG 6 HRLY TAB MESACOL 800 MG 6 HRLY K⁺ REPLACEMENT BLOOD TXN IV ANTIBIOTICS IV MgSO₄ IV ALBUMIN TPN 53 Treatment Day 01-07:

Course…. : 

Despite adequate trial of intensive regimen : Stool frequency 6-8/d Progressive worsening of anemia despite Txn Progressive hypoalbuminemia Persistent Hypokalemia GI surgeons consulted for possible emergency total proctocolectomy 54 Course….

Surgical indication : 

Life threatening: Toxic megacolon Colonic perforation Massive uncontrollable hemorrhage Medical treatment related: Intolerable/unacceptable side effects Medically refractory disease Cancer-related : Colonic dysplasia/malignancy Surgical indication 55

Course…. : 

Day 08: IV INFLIXIMAB (5MG/KG BW IN 200 ML NORMAL SALINE OVER 2 HRS, WITH NO PREMEDICATION/ANPHYLAXIS EVENTS) Course…. 56

Slide 57: 

57 N ENG J MED353:28 WWW.NEJM.ORG DEC 8 2005

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58

Course after infliximab : 

Day 8-12: Stool frequency 2-3/d Scanty blood in stools Sense of general well being Course after infliximab 59

Course…. : 

Therapy continued: TAB PREDNISOLONE 60 MG OD TAB MESACOL 800 MG 6 HRLY K⁺ REPLACEMENT TAB PANTOPRAZOLE 40 MG OD HEMATINICS Course…. 60

At discharge…. : 

Day 15: VITALS NORMAL STOOLS: 2-3/DAY NO PAIN ABDOMEN At discharge…. 61

At follow up…. : 

Review in OPD after a week: Follow up: stool frequency: 2/day No blood in stools Sense of gen well being Same treatment continued Planned for gradual tapering of prednisolone over next 12 weeks At follow up…. 62

Biologics : 

Generally speaking, therapeutic or diagnostic products consisting of, or derived from, living organisms “ a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product which is applicable to the prevention, treatment, or cure” of a disease or condition of human beings 63 Biologics

Biologics : 

Therapeutic protein products Cytokines Interferons Enzymes Thrombolytics Monoclonal antibodies Immunoglobulin products Immunomodulators Somatic cells Human tissue and cellular products Gene therapy products Xenotransplantation products 64 Biologics

Monoclonal antibody : 

Initially produced in mice in 1984 using Hybridoma technique Among the most important class of drugs Produced from a single B cell clone Directed against a specific epitope Monoclonal antibody 65

International Nonproprietary Names (INN) Nomenclature : 

INN for monoclonal antibodies (mAbs) are composed of a prefix, a substem A, a substem B and a suffix. The common stem for mAbs is -mab, placed as a suffix The stem -mab is to be used for all products containing an immunoglobulin variable domain which binds to a defined target International Nonproprietary Names (INN) Nomenclature 66

Substem A indicates the target (molecule, cell, organ) class : 

Substem A indicates the target (molecule, cell, organ) class 67

Substem B indicates the species on which the immunoglobulin sequence of the mAb is based : 

Substem B indicates the species on which the immunoglobulin sequence of the mAb is based 68

Infliximab : 

Infliximab is a chimeric IgG₁ (human-murine) monoclonal antibody that binds to human tumor necrosis factor alpha (TNF- α), a pro-inflammatory mediator in multiple chronic inflammatory conditions 69 Infliximab

Infliximab : 

Binds to soluble and membrane-bound TNF- α, preventing binding of TNF- α to its receptor 70 Infliximab

Infliximab : 

Infliximab has been FDA-approved for use in: Crohn's disease Ulcerative colitis Rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis. 71 Infliximab

Rationale for use of Infliximab in Ulcerative colitis : 

Tumor necrosis factor-α, a key proinflammatory cytokine, is found in increased concentrations in the blood, colonic tissue, and stools of patients with ulcerative colitis. 1. Murch SH, Lamkin VA, Savage MO,Walker-Smith JA, MacDonald TT. Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 1991;32:913-7. 2.Murch SH, Braegger CP, Walker-Smith JA, MacDonald TT. Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut 1993;34:1705-9. 3. Braegger CP, Nicholls S, Murch SH, Stephens S, MacDonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992;339:89-91. 72 Rationale for use of Infliximab in Ulcerative colitis

Side Effects : 

Nausea, vomiting Anaphylaxis -like reactions Lupus like reaction Serious infections 73 Side Effects

OPD review on 14 Jan 201 : 

Rectal mucosal biopsy HPE report (BHDC) Biopsy no. B/3834/10 Mucosal ulceration, marked architectural distortion, shortening, budding and branching of glands Cryptitis+ Dense mixed inflammatory infiltrate in lamina propria with plasma cells & lymphocytes No dysplasia No CMV inclusion bodies Rectal mucosal biopsy for CMV PCR at AH(R&R) > 2 million copies/mL 74 OPD review on 14 Jan 201

Plan: : 

IV Ganciclovir over next 14 days wef 15 Jan 2011 75 Plan:

Thanks for your attention : 

MEDICAL DIVISION,BHDC Thanks for your attention

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