CASE PRESENTATIONDr. M. Qasim Khan,

PGR West Medical Ward,

Mayo Hospital, Lahore.

SIMPLICITY

“Simplicity is the ultimate sophistication.”

Leonardo da Vinci

“There's something really appealing about the simplicity of black-and-white images”

Joseph Gordon-Levitt

“Elegance is achieved when all that is superfluous has been discarded and the human being discovers simplicity and concentration: the simpler and more sober the posture, the more beautiful it will be.”

Paulo Coelho

Patient’s Biodata

Name: Nazir Ahmed Age: 35 YearsSex: MaleOccupation: GardenerAddress: Gullian Chak No 9, PattokiD.O.D: 4/8/14M.O.D: Emergency DepartmentEthnicity: PunjabiLanguage: Punjabi, Urdu Religion: Islam

Presenting complaintsBleeding per rectum 6monthsloose motions 2 monthsweight loss 2 monthsAbdominal Pain 20 days.fever 1 monthHistory of presenting illness:My patient normotensive and normoglycemic was in USOH 6 months back when he started noticing streaks of fresh blood along with stools . Stools were soft in consistency 1 to 2 episodes per day not associated with abdominal or per rectal pain. He took medicine (not known) from a local doctor for 1 month and noted improvement but not total resolution . Then he took medicine from a hakeem for 15 days and complained of loose stools 3-4 episodes soft to watery in consistency yellow to brown in color not associated with abdominal pain or blood. He changed the medicine from other hakeem but noted relapse of stools with fresh blood . –PTO-

For 2 months he has been complaining of loose stools initially 3 -4 episodes per day , watery in consistency dark brown in color, with mixed fresh blood and also complained of occasional watery discharge (mucus) per rectum mixed with fresh blood . He came to Lahore and diagnosed as hemorrhoids for with hemorroidectomy was done 20 days back. After that loose stools increased to 10 to 12 episodes per day associated with tenesmus and abdominal pain pain. Pain was on the lower abdomen, not radiating, increased before defecation and decreased after. He also complained of fever for 1 month remitting relapsing high grade mostly at night associated with chills that relieved on medication for 1 month. H/O anorexia and weight loss for 2 months his weight been decreased from 72 to 51 kg in 3 months . Not associated nausea, vomiting, joint pain.

Past History:A frequent history of lower leg swelling of veins for 10 years. H/O RTA 5 years back.No H/O surgery, allergies or psychiatric illness.Drug History:History of occasional use of hakeem medication since childhood. H/O azathioprine 100mg daily for 2 weeks, H/O mesalamine 2400 mg daily and sulfasalazine tabs 1500mg daily for 2 weeks. IV and oral steroids . Family History:H/O Hepatitis C in motherDiabetes in Father . Hemorrhoids in brother.

Personal History :He is married for 10 years with two children . Currently unemployed . Non smoker, No h/o TB, DM or hypertension.Socioeconomic History : He belongs to poor class . Lives in a joint family of 12 persons in a 10 Marla house .

Systemic Review General : H/O weight loss for 2 months. Anorexia for 2 months, H/O on and off fever high grade associated with chills for 1 month, H/O fatigue and inability to work for 2 months . The patient is using Diaper for 20 days.Skin: H/O Rash, redness and itching of posterior scrotal skin for 5 days. HEENT: No H/O headache or head trauma.Eyes: No H/O Eye pain redness, dryness or recent changes in vision.Ears: No H/O hearing loss, discharge, dizziness or ringing in ear.Nose: No recent H/O runny nose, stuffy nose or nose bleeds.Throat: H/O white & yellow coating of tongue & oral mucosa for 5 days that doesn’t come off on scratching. H/O Brownish-yellow patches on teeth for 10 yrs. No recent H/O sore throat or oral ulcers.

Neck: No H/O soreness, stiffness , enlarged nodes or lumps on neck.Heart: No known H/O of heart problems, hypertension, high cholesterol, chest pain, palpitations, SOB, orthopnea, PND or lower extremity edema.LUNGS: No H/O lung disease, asthma, TB or TB contact, pneumonia. NO recent H/O cough, sputum, wheezing, SOB .GI: H/O bleeding per rectum for 6 months, Loose motion for 2 months, Abdominal pain and tenderness 20 days H/O hemmorhoids for which hemorrhoidectomy was done 20 days back (Discussed in detail in HOPI). No H/O constipation, nausea, vomiting, heart burn or difficulty swallowing.

Urinary: No H/O change in frequency, burning or painful urination and other lower urinary tract symptoms.Genital: Sexually inactive for 3 months . H/O Rash, redness and itching of posterior scrotal skin for 5 days. No H/O penile sores, discharge, testicular pain or enlargement.Peripheral vascular: A frequent history of lower leg swelling of veins for 10 years that come and goes .Musculoskeletal: No H/O muscle or joint pain, cramps or stiffnessNeurologic: No H/O seizures, loss of consciousness, numbness, tingling, shooting pain or tremors

Hematological: H/O fatigue and pallor for last 4 months . H/O 3 blood transfusions in last month.Endocrine: No H/O diabetes, thyroid problems, increased thirst, urination, heat or cold intolerance.Psychiatric: H/O mild depression for last 2 months, No h/o suicidal ideation mood swings, memory problems, personality changes, nervousness or anxiety.

SummaryA 35 year old male presented with C/O fresh bleeding per rectum for 6 months, Loose stools for 2 months that increased from 3-4 to 10-12 episodes per day in last 20 days , H/O weight loss from 72 to 51 kg in last 2 months and associated anorexia, C/O high grade fever remitting and relapsing relieving on medication and mostly at night for 1 month .C/O non radiating Lower abdominal pain and tenderness and tenesmus for 1 month . H/O hemorrhoidectomy 20 days back, C/O oral thrush and jock itch for 5 days.

Differential Diagnosis:Inflammatory Bowel DiseaseIntestinal TBInfective enterocolitis (Chronic schistosomiasis, Amebiasis, Cytomegalovirus colitis, salmonellosis ETC ) Cathartic ColonIschemic colitisChronic DiverticulitisToxic megacolonNSAID enteropathyMalignancy

PHYSICAL EXAMINATION

General Survey:The patient is a normal build, young adult Indo-Aryan male who appears his stated age of 35 and is in mild distress. He is alert and oriented to person,place and time. Patient is lying down but can ambulate without difficulty and moves freely. He appears well-groomed, clean, and is dressed in a shalwarqameez. Patient talks freely and is cooperative but appears to be somewhat anxious.HR: 90/mint, BP: 130/80,RR:17/mit, Temp: 99 FPain: Mild abdominal painHeight: 5‘6“, wt: 51 kg

SKIN:Pallor +veJaundice –veCyanosis –vePalmar erythema -veSmooth Texture of skin, slightly warm, humid, normal turgor, . No apparent Skin Lesion in the exposed area from waist upwards and feet.NAILS: Clubbing –veCapillary refill 3 secondsNo Nails deformity or pathology in both hands and feet.

Head - normocephalic, no masses /lesions, cicatrices, malar flushing .Eyes - visual fields intact, PERRLA , conjunctiva palor, sclera white, anicteric, EOMI, no ptosis, Fundoscopy not done.( Normal Fundoscopy: red reflex present. discs flat w sharp margins,vessels present w/o crossing defects, retinal hemorrhages)Ears – Hearing appears Normal. Otoscopy not done (Normal otoscopy: TM's non-injected, good light reflex, no protrusion or retraction; Normal hearing tests: Webermidline, Rinne ac>bc, Whisper test 3:3)Nose - nares patent, no deformity, septal deviation or perforation.

Throat – Pharanx normal, palate rises symmetrically, gag present.MOUTH - Buccal mucosa, moist and intact, creamy-white curdlike patches with yellow crusted coating on tongue that doesn't remove on scratching (Oral Thrush), tonsils present, dentition intact, Brownish-yellow patches and scales on teeth, tongue midline w/o fasciculations.Neck & Axilla - no LAD ,masses,or thyromegaly/focal lump,carotid pulses 2+ & = (B), no bruits, neck supple full ROM, trachea midline.

Back, Thorax & Lungs - Chest expansion symmetric, Clear to A&P, Normal vesicular breathing, eupnoea, no adventitioussoundsCardiovascular – JVP at 450 not raised, carotid arteries nl

upstroke & amplitude bilaterally, Inspection: no lifts or heaves, PMI not visible. Palpation: no palpable

parasternal impulses, heaves or thrills .PMI palpable in 5th ICS, MCL, nl size.Auscultation: S1- heard best at apex, nl intensity S2- heard best at base, nl splitting, A2 > P2 no m/r/g

ABDOMENObservation: Normal boat shaped abdomen, umbilicus inverted and situated centrally, no stria, scar marks.Auscultation: bowel sounds 2 cycles/min, no bruits Palpation: Superficial- tenderness in Left lower quadrant, hypogastrium and right lower quadrant, guarding –ve, no masses. Deep- Tenderness more in left lower quadrant, then hypogastrium and right lower quadrant, rebound tenderness

negative, Liver Palpation- liver edge not palpablePercussion - Size-12 cm in R midclavicular line Spleen not palpable, B/L Kidneys not palpableFemoral Pulses: 4 / 4 bil equal, no bruit

musculoskeletal - gait normal, able to tandem walk, no Rhomberg's sign; joints and muscles symmetric, noswelling, masses, deformity or tenderness to palpation; no heat or swelling of joints; full ROM; musclestrength 5/5- able to flex against resistance & w/o tenderness.genitalia/rectum - Rash, redness and itching of posterior scrotal skin and groin folds. no lesions, inflammation or discharge from penis, mucous discharge mixed with blood apparent from anus:No fistula or lesions in perianal area. PR not done. Stool dark brown watery mixed with blood, guaiac +ve .

Nervous - CN II-XII grossly intact, alert oriented, cooperative, sensory - pinprick, light touch & vibration intact; proprioception normal, motor - no atrophy, weakness, tremors or clonus; RAM, finger-to-nose/heel-to-shin intact; Rhomberg negative .DTR's - all 2+ & = (B); Babinski; toes downgoing. Naming & repetition intact; memory 3:3; (B) Pronator drift nl, gaze normal; extinguishesL side to direct sen. stim.Cranial Nerves:All cranial nerves are Intact

Summary:A 35 year old normal build, young adult Indo-Aryan male with following Vitals HR:90/mint, BP: 130/80,RR:17/mit,Temp: 99 F Pain: Mild abdominal pain.He is Pallor, has Abdominal tenderness; more in the left lower quadrant then hypogastrium and right lower quadrant. Has mucous discharge mixed with blood apparent from anus & diaper filled with dark brown watery stool mixed with blood. Has oral thrush and jock itch .

Differential Diagnosis:Inflammatory Bowel DiseaseIntestinal TBInfective enterocolitis (Chronic schistosomiasis, Amebiasis, Cytomegalovirus colitis, salmonellosis ETC ) Cathartic ColonIschemic colitisChronic DiverticulitisToxic megacolonNSAID enteropathyMalignancy

LABORATORY FINDINGS

CBC:wbc 6.2*103/ ulHb 8.2 mg/dlHCT 28.4 %MCV 92.2 fLMCH 26 pgMCHC 28.9 g/dlPLT 259 *103/ ulLymp 7.5 %Neut 90.4 %RDW 70.6 fLPDW 9.1 fL

LFT’s:Ast: 58ALT: 54Bil: 0.9T.P: 6.5Alb: 2.8RFT’S:urea: 34Creat: 1.2S/E :Na+ : 133K+ : 3.3Cl- : 97

TFT’sT3: 97 ng/dL (NR : 58-159)T4: 89 nmol/L (NR : 66-181) TSH: 1.6 mIU/L (NR : 0.27-4.2)U/E : unremarkableCxray: NormalUltrasound Abdomen : NormalStool Cytology: WBC numerous, RBC Numerous, No Ova, Cyst or Parasite seenStool Culture: No Growth of Salmonella, Shigella or vibrio species after 48 hours incubation at 370 C

PR Proctoscopy :2nd degree hemorrhoids at 3,7 and 11 ‘o Clock .There is also altered blood from higher Up.COLONOSCOPY:PR exam Blood stained. Colonoscopy seen uptosplenic flexure of Colon; Erythematous and friable mucosa with multiple ulcerations and pseudopolys. Multiple biopsies taken for histopathological exam.

Biopsy Report :Immunohistichemistry : Cytokeratin positive in epithelial cellsDiagnosis: Extensive ulcerations and inflamed granulation tissue. Focus of Large Bowel Mucosa Shows Reactive Changes.No definite Dysplasia or Malignancy Seen

Final DiagnosisSevere Ulcerative Colitis

Treatment Given in the ward:Azathioprine 50mg BDmesalamine 800 mg TDSSulfasalazine tabs 500mg TDSMesalamine Enema BDInj Hydrocortisone 250 mg TDSInj CiprofloxacinInj MetronidazoleInj Omeprazole

Further Evaluation:pANCACT AbdomenBarium Enema ….

Ehhheewww .. Take a breath !!

Discussion

Inflammatory Bowel Disease

Overview

DefinitionsHistoryEpidemiology PathophysiologyClinical featuresDiagnosis with differentialsComplicationsManagement of disease Ongoing research

IBD

Inflammatory bowel disease is an idiopathic inflammatory intestinal disease resulting from an inappropriate immune activation to host intestinal microflora.

Types of IBD are

Ulcerative colitis

Crohn’s disease

Indeterminate colitis

History

Morgagni provided a description of intestinal inflammation characteristic of Crohn's disease in 1761.

After the identification of the tubercle bacillus by Koch in 1882 it was possible to describe persons with ileocecal disease similar to intestinal tuberculosis but lacking the organism.

In 1932, the landmark publication of Crohn, Ginzburg, and Oppenheimer called attention to “terminal ileitis” as a distinct entity and chronic disease.

History

The term “Regional enteritis” embraced the focal nature of the process, but failed to incorporate knowledge of the possibility of disparate sites of involvement within the GI tract and multisystemic nature.

The term “Granulomatous enterocolitis” lost acceptance when it became clear that granulomas were not a sine qua non of the diagnosis.

History

The name “Crohn's disease” has been adopted to encompass the many clinical presentations of this pathologic entity. But for the alphabetic priority these authors chose Crohn's disease.

IT might well have been Ginzburg's or Oppenheimer's disease.

Epidemiology

The incidence of UC is 3 times higher than that of CD. But recent data suggest that the incidence of CD is increasing.

The highest rates of IBD are seen in developed countries, and the lowest in the developing regions;

Racial, sexual, and age-related differences

Highest rates are seen in the Jewish populations

The M:F ratio is approximately 1:1 for UC and females having a slightly greater incidence in CD

The age distribution of newly diagnosed IBD cases has double peak, the 1st peak in people aged 15-40 years. A 2nd smaller peak in patients aged 55-65 years

Two major types of IBD

Crohn’s disease

Incidence – 5.8 per 100,000 persons

Prevalence - 116 per 100,000 persons

Ulcerative colitis

Incidence – 7.8 per 100,000 persons

Prevalence - 156 per 100,000 persons

Minnesota study, 2009

South Asia perspective

Probert CS and colleagues found out that the minimum incidence on CD is 0.14/1lakh persons-years,

Hindus have a much lower incidence of CD than Europeans

In Pakistan, there is much less extraintestinal disease in both UC and CD than is reported from the West (where up to 25% of patients have extraintestinalmanifestations if arthralgia's are included). In Pakistan, few patients have perianal or fistulizing disease.

Etiopathogenisis

Genetic susceptibility

Environmental factors

Host immunity

Genetics

Increased risk among first-degree relatives is 14 to 15 times higher than that of the general population

Jews are at a 2-4 fold higher risk of developing IBD than non-Jews of the same geographic location

Studies in twins suggest that genetics is a more powerful determinant of disease for CD(67%) than for UC(13%).

Genetics Crohn’s disease Ulcerative colitis

anti-OmpC ab is more common among healthy family members of CD probands

3 imp. pathways in pathogenesis of CD

NOD2/CARD15

Autophagy-related genes

Interleukin (IL)-23

MDR 1

HLA-DR1

HLA-DR3,DQ2

ENVIRONMENTAL FACTORS

Rising incidence of Crohn's disease

Associated with higher socioeconomic status

Breast-feeding to be protective for IBD

Increased risk among women who use OCPs

Increased intake of refined sugars and a paucity of fresh fruits and vegetables

ENVIRONMENTAL FACTORS

UC is more common among nonsmokers than current smokers, whereas CD is more prevalent among smokers

UC is more common in current light smokers than in heavy smokers

Several infectious organisms, including mycobacteria and viruses, have been implicated in the pathogenesis of IBD

Humoral Immunity

A marked increase in the number of plasma cells

Proportional increase occurs in immunoglobulin IgG synthesis

IgG synthesis in UC is in the IgG1 and IgG3 subclasses, whereas in CD it is IgG2

Autoantibody in UC patients is pANCA, whereas in CD, Anti-CBir1, Anti-OmpCor Anti I2 antibodies are seen.

Cellular Immunity

Bacteria prompt immune responses through PRRs

Activation of the PRRs results in downstream activation of NF-κB, which then stimulates the transcription of various proinflammatory cytokines

Based on the cytokines they produce, CD4+ T cells have been divided into three major immune phenotypes:

T helper 1 – CD (IL-12)

T helper 2 - UC

T helper 17 (IL-23)

Pathology of CD

Focal intestinal inflammation is the pathologic hallmark of CD

Characterised by presence of aphthae on a background uninvolved bowel

Minute superficial ulcers, ranging from barely visible to 3 mm, and are surrounded by a halo of erythema

Coalesce into Linear or serpiginous ulcers with a stellate appearance.

Cobblestoned appearance

Crohn’s Disease

Crohn’s Disease

Intestinal inflammation in CD is a transmural process

The location of disease,

35 – 50 % - both ileum and colon.

35 % - small intestine

15- 30% - isolated colonic disease

Large ulcers, sinus tracts, and strictures, adhesion of bowel loops are late features of CD

fat wrapping - creeping of mesenteric fat onto the serosal surface of the bowel.

Microscopic findings

Granulomas are highly characteristic of CD

Prevalence of granulomas in CD

15% in endoscopic series

70% in surgical series

Pyloric metaplasia

The presence of lymphoid aggregates in the submucosa and external to the muscularis propria is a reliable sign of CD even when granulomas are not seen

TNF is the key cytokine in the formation of granulomas.

Granuloma

Ulcerative colitis

At the time of initial presentation, approximately

45% -limited to the rectosigmoid,

35% - extending beyond the sigmoid

20% of patients have pancolitis

Continuous and symmetrical involvement

Mucosa appears hyperemic, edematous, and granular in mild disease becomes hemorrhagic, with visible punctate ulcers as it progresses.

•In long-standing UC.

Epithelial regeneration with recurrent attacks results in the formation of pseudopolyps

Atrophic and featureless colonic mucosa, associated with shortening and narrowing of the colon

Microscopy

Inflammation in UC characteristically is confined to the mucosa

Neutrophilic infiltration of colonic crypts leads to cryptitis & crypt abscesses

Cryptitis is associated with discharge of mucus from goblet cells. Results in the characteristic histopathology of goblet cell mucin depletion, formation of exudates, and epithelial cell necrosis.

Crypt architectural distortion or dropout of glands.

Clinical features

Manifestations of inflammatory bowel disease

Recurrent abdominal pain and diarrhoea.

Cramping

Irregular bowel habits, passage of mucus without blood or pus

Grossly bloody stools, occasionally with tenesmus: Typical of UC, less common in CD

Growth retardation and delayed or failed sexual maturation in children

Perianal disease in 50% of patients with CD

Patients with UC

Rectal bleeding

Frequent stools- Mucous discharge from the rectum

Tenesmus (occasionally)

Lower abdominal pain and severe dehydration from purulent rectal discharge (in severe cases, especially in the elderly)

WHO- symptoms suggestive of inflamed GIT

Diarrhea: mucus or blood may be present in the stool; can occur at night; incontinence may occur.

Constipation: this may be the primary symptom in UC limited to the rectum; obstipation may occur and may proceed to bowel obstruction

Bowel movement abnormalities: pain or rectal bleeding may be present, as well as severe urgency and tenesmus

Abdominal cramping and pain: commonly present in the right lower quadrant in CD; occur periumbilically or in the left lower quadrant in moderate to severe UC

Nausea and vomiting: occurs more often in CD than in UC

Systemic symptoms

Weight loss

Fever

Sweats

Malaise

Arthralgias

A low-grade fever may be the first warning sign of a flare.

Signs

Fever

Tachycardia

Dehydration

Toxicity

Pallor, anemia

Toxic megacolon: patients appear septic, high fever with chills tachycardia & increasing abdominal tenderness & distention

Mass in the right lower abdominal quadrant: May be present in CD

Perianal disease of CD

.1Skin lesions- include maceration, superficial ulcers, abscesses, and skin tags

type 1 (elephant ears) are typically soft and painless and large

type 2 are typically edematous, hard, and tender.

.2Anal canal lesions - fissures, ulcers, and stenosis

.3Perianal fistulas.

Unusual Presentations of CD

•Gastroduodenal - H-pylori-negative peptic ulcer disease, dyspepsia or epigastricpain as the primary symptoms

•Esophageal - < 2% of patients.

•Dysphagia, odynophagia, substernal chest pain, and heartburn

•Mouth ulcers

•Esophageal stricture and esophagobronchial fistula

•acute granulommatous appendicitis -

DISEASE BEHAVIOR IN CD

Aggressive fistulizing disease

anti-OMPC

pANCA

25% of pts present with an intra-abdominal abscess

Indolent cicatrizing disease

NOD2 variants

anti-CBir1

Anti I2

Aggressive fistulizing disease

Fistulas are manifestations of the transmural nature of CD

Perianal fistulas are common and occur in 15% to 35% of patients.

Enterovaginal fistulas occur in women

Enterovesicular - recurrent polymicrobial UTI or as frank pneumaturia and fecaluria.

Enterocutaneous fistula after appendectomy

Other types- enteroenteric, enterocolonic, and colocolonic fistulas

Stricture

Stricture is another characteristic complication of long-standing inflammation

Symptoms can include colicky, postprandial abdominal pain and bloating, punctuated by more-severe episodes, and often culminating in complete

obstruction.

String sign - markedly narrowed bowel segment amid widely spaced bowel loops

CDAI

In remission <150

Mild-moderate 150-220

Moderate-severe 220-450

Fulminant >450

Ulcerative Colitis: Disease Presentation

Mild Moderate Severe

Bowel movements <4/day 4-6/day >6/day

Blood in stools Small Moderate Severe

Tachycardia None <90/min >90/min

Fever None <99.5F >99.5F

Anemia Mild Moderate Severe

ESR <30 >30

Endoscopy Erythema, decreased vascular

pattern, fine granularity

Marked erythema, coarse granularity,

absent vascular markings, contact

bleeding, no ulcerations

Spontaneous bleeding,

ulcerations

EXTRAINTESTINAL MANIFESTATIONS

Musculoskeletal

Clubbing

Arthritic manifestations

Peripheral arthropathy - 16% to 20%

Pauciarticular arthropathy (type I, affecting four or fewer joints)

Polyarticular arthropathy (type II, with five or more joints affected)

Axial arthropathies - 3% to 10%

Metabolic bone disease

Granulomatous vasculitis, periostitis and amyloidosis.

Mucocutaneous

Pyoderma gangrenosum

Erythema nodosum

Granulomatous inflammation of the skin

Aphthous ulcers of the mouth

Angular cheilitis

Pyoderma Gangrenosum

ErythemaNodosum

Ocular

Occur in 6% of patients .

Episcleritis

Scleritis

Uveitis - the posterior segment

Keratopathy and night blindness

Hepatobiliary

Gallstones

Asymptomatic and mild elevations of liver biochemical tests

PSC more often is associated with UC

autoimmune hepatitis.

Vascular

venous thromboembolism

arterial thrombosis.

Renal and Genitourinary

Inflammatory entrapment of the ureter

Uric acid and oxalate stones.

Membranous nephropathy &Glomerulonephritis

Renal amyloidosis.

. Penile and vulvar edema

DIFFERENTIAL DIAGNOSIS

Intestinal tuberculosis

Irritable bowel syndrome

Anorexia Nervosa &Bulimia

Ischemic bowel disease

Neoplasia, including carcinoma and lymphoma

Infectious diarrheas & Clostridium Difficile Colitis

Celiac Sprue

Collagenous and Lymphocytic Colitis

Abdominal pain, gastrointestinal bleeding, and/or intestinal ulceration

Ischemic colitis

Intestinal tuberculosis

Radiation-induced colitis

Arteriovenous malformations

NSAID enteropathy

Behcet disease

Colorectal malignancy

Diarrhea

AIDS

Celiac disease

Microscopic colitis

Irritable bowel syndrome

Lactose intolerance

Functional diarrhea

Gastrointestinal infections

Behcet disease

Colorectal malignancy

Investigations

Investigations

CBC

Nutritional evaluation: Vitamin B12 , iron studies, folate & other nutritional markers

ESR and CRP levels

Fecal calprotectin level

Serologic studies: pANCA, ASCA, anti-CBir1

Stool studies: Stool R/M, C/S, evaluation for Clostridium difficile toxin

Imaging studies

Upright chest and abdominal radiography

Barium double-contrast enema radiographic studies

Abdominal ultrasonography

Abdominal/pelvic computed tomography scanning/magnetic resonance imaging with enterography

Colonoscopy, with biopsies of tissue/lesions

Upper gastrointestinal endoscopy

Capsule enteroscopy/double balloon enteroscopy

Plain radiograph

In severe disease, the luminal margin of the colon becomes edematous and irregular.

Thickening of the colonic wall often is apparent on a plain film

Plain films also are useful for detecting the presence of fecal material.

The presence of marked colonic dilatation suggests fulminant colitis or toxic megacolon.

Toxic megacolon

Barium studies

Aphthous ulcers, a coarse villus mucosal pattern, and thickened folds.

Pseudo sacculation of the antimesenteric border

Cobblestone appearance

Fistulas, sinus tracts, and fixed strictures

The earliest radiologic change of UC seen is fine mucosal granularity

Crohn’s colitis

String sign

lead-pipe or stove-pipe appearance

CT Enterography

The sensitivity - 82%

specificity - 89%

accuracy - 85%.

Mural enhancement

Mesenteric fat stranding

The comb sign

Pseudosacculations

Comb sign

MR enterography

Intestinal wall thickening, submucosal edema, vasa recta engorgement, and lymphadenopathy are signs of active diseas

FIESTA images can add information regarding the functional status of fibrotic segment

MRI images yield a diagnostic accuracy of 91%.

Enteroscopy

Aphthous ulcers

Mucosal edema

Cobblestoning

Luminal narrowing

Rectal sparing is more specific before treatment has been initiated.

Skip lesions - Crohn’s does not affect the intestinal mucosa in a continuous fashion

Colonoscopy

The hallmark of UC is continuous inflammation that begins in the rectum.

The earliest endoscopic sign of UC is a mucosal erythema and edema

As disease progresses, the mucosa becomes granular and friable.

In severe inflammation, the mucosa may be covered by yellow-brown mucopurulentexudates associated with mucosal ulcerations.

Ulcerative Colitis

Uses of colonoscopy

Determine the extent and severity of colitis

Provide tissue to assist in the diagnosis.

Therapeutic use is stricture dilation

Tablet Enteroscopy

Swallows encapsulated video camera

Transmits an image to a receiver outside the pt.

It is most commonly used for finding obscure sources of GI blood loss,

The images can find ulcerations associated with CD if endoscopy and colonoscopy are unrevealing

The major risk is the potential to get lodged at the point of a stricture

Complications of CD

Perforation

Abscess formation

Stricture & small bowel obstruction

Nutritional deficiencies

Cancer: small bowel adenocarinoma

Cancer: colon???

Complications of UC

Toxic Megacolon:

Defined as a transverse or right colon with a diameter of >6 cm, with loss of haustration in patients with severe attacks of UC.

It occurs in about 5% of attacks and

It can be triggered by electrolyte abnormalities and narcotics.

About 50% of acute dilations will resolve with medical therapy alone

Urgent colectomy is required for those that do not improve

Complicatins of UC

Colon adenocarcinoma

After 8–10 years of colitis, annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals should be performed

extensive mucosal involvement (pancolitis)

family history of carcinoma of the colon.

Perforation

Massive hemorrhage

IBD - Treatment

Medications used in treatment

5- ASA

Antibiotics

Glucocorticoids

Immune modulators

Biologics

5- ASA

Mainstay of therapy for mild to moderate UC and CD

Effective at inducing remission in both UC and CD( ?)

Maintains remission in UC

No role in maintenance of CD

Side effects

Sulfasalazine Anorexia, dyspepsia, nausea and vomitingHemolysis

Neutropenia-AgranulocytosisFolate deficiency

Reversible male infertilityNeuropathy

Sulfa-free 5-ASAs (mesalamine, olsalazine, balsalazide)

Headache; drug fever; rash; paradoxical disease exacerbation; pancreatitis; hepatitis;

pericarditis; pneumonitis; nephritis; secretory diarrhea (olsalazine)

Antibiotics

To treat perianal disease, fistulas, and active luminal Crohn's disease.

Beneficial in healing perianal fistulas.

Metronidazole demonstrated a prophylactic effect on endoscopic and clinical recurrence at one year

Ciprofloxacin 1 g/day to be equivalent to mesalamine 4 g/day in achieving remission of mild to moderately active CD at week 6

Combination was comparable with glucocorticoids in achieving remission over 12 weeks

Glucocorticoids

•Moderate-to-severe cases benefit from glucocorticoids.

•Oral prednisone is started at doses of 40–60 mg/d

•Parenteral glucocorticoids

•Hydrocortisone- 300mg/d

•Methylprednisolone - 40–60 mg/d

•Topically applied glucocorticoids are also beneficial for distal colitis

•Budesonide is used for 2–3 months at a dose of 9 mg/d, then tapered.(entocort)

•No role in maintenance therapy in either UC or CD.

Pearls of glucocorticoid use

Use an effective dose

Do not overdose.

Do not treat for excessively short periods.

Do not treat for excessively long periods.

Anticipate side effects.

Patients are candidates for immunomodulators or anti-TNF agents

If flares are frequent (>1-2 times),

If the duration of steroid use is prolonged

If reduction of the steroid dose causes recurrence of symptoms(steroid dependent),

If steroids do not appear to be working (steroid refractory)

AZATHIOPRINE AND 6-MERCAPTOPURINE

Purine analogs that interfere with nucleic acid metabolism

Azathioprine - 2.0 to 2.5 mg/kg/day

6-MP -1.0 to 1.5 mg/kg/day

Used in patients with IBD in whom remission is difficult to maintain with the ASA alone

Used as glucocorticoid- sparing agents in upto 2/3rds of pts

Patients who failed with antibiotics for a fistula

Selection of Pt. for Azathioprine

AGA recommends that Pts should undergo an assessment of the thiopurinemethyltransferase genotype before starting therapy with AZA or 6-MP.

Individuals who have low enzyme activity or are homozygous deficient in the TPMT mutation are at risk of very severe leukopenia, with potential septic complications, and are not be good candidates for therapy with these drugs.

how long to continue?

A randomized, controlled trial demonstrated a clinical relapse rate of 21%, 18 months after withdrawal of azathioprine in patients who had been in remission for at least 3.5 years on the drug, compared with a relapse rate of only 8% in the group who continued azathioprine.`

Side effects

Abnormal liver biochemical test results- LFT

Bone marrow suppression- CBC

Hypersensitivity reactions (fever, rash, arthralgia)

Infections

Lymphoma

Nausea, abdominal pain, diarrhea

Pancreatitis

Methotrexate

Dihydrofolate reductase inhibitor

IM or SC MTX (25 mg/week) is effective in inducing remission and reducing glucocorticoid dosage;

15 mg/week is effective in maintaining remission in active CD.

Potential toxicities include leukopenia, hepatic fibrosis and Hypersensitivity pneumonitis

CYCLOSPORINE

Lipophilic peptide with an inhibitory effects on both the cellular and humoralimmune systems.

Dose is 2–4 mg/kg per day IV, in severe UC that is refractory to IV glucocorticoid

Hypertension, gingival hyperplasia, hypertrichosis, paresthesias, tremors, headaches, and electrolyte abnormalities are common side effects.

Renal function and seizures are dose limiting side effects

BIOLOGIC THERAPIES

Anti-TNF therapy

•Infliximab, Adalimumab & certolizumab pegol

Treatment of moderate to severe active CD or UC.

Effective in CD patients with refractory perianal and enterocutaneous fistulas

If a patient does not have an initial response , currently it is considered futile to try another.

Infliximab

INDUCTION- 3 separate infusions of 5 mg/kg for moderate to severe IBD at weeks 0, 2, and 6

MAINTENANCE- infusions every 8 weeks

Before anti-TNF agents are administered, screening should be done for coexistent infection with perianal and abdominal abscess (includingMycobacteriumtuberculosis), and caution is advised if a patient is a carrier for the hepatitis B virus.

Risk factors for relapse include

male sex

leukocyte count > 6.0 × 109/L

CRP > 5.0 mg/L

Fecal calprotectin > 300 µg/g.

Side effects

The FDA reviewed 147 postmarketing reports of leukemia and 69 cases of new-onset psoriasis

Other morbidities

acute infusion reactions

severe serum sickness.

infections.

optic neuritis,

seizures,

new-onset or exacerbation of MS

Novel therapies

CDT-cell marker therapies

mesenchymal stem cells

Thalidomide

Interleukin (IL)-11

•UC -Anti-inflammatory proteins

Nicotine patch

butyrate enema

Heparin

Step up approach

Step I – Aminosalicylates -For treating flares and maintaining remission; more effective in UC than in CD

Step IA – Antibiotics:

Used sparingly in UC (limited efficacy, increased risk for antibiotic-associated pseudomembranous colitis);

In CD, most commonly used for perianal disease, fistulas, intra-abdominal inflammatory masses

Step II – Corticosteroids (intravenous, oral, topical, rectal): For acute disease flares only

Step III – Immunomodulators: Effective for steroid-sparing action in refractory disease; primary treatment for fistulas and maintenance of remission in patients intolerant of or not responsive to aminosalicylates

Step IV – : Tend to be disease-specific (ie, an agent works for CD but not for UC, or vice versa)

Management of remission

A general rule of thumb is that once remission is achieved, the medications used to achieve remission should be continued, except steroids, which should be tapered off, because they have no role in maintaining remission

Adjunctive Therapies

Antidiarrheal (diphenoxylate and atropine, loperamide, cholestyramine)

anticholinergic agents(eg, dicyclomine, hyoscyamine)

Vitamin supplementation

Iron supplementation

Smoking cessation in CD pts

Patients with active CD respond to bowel rest, along with TPN, but does not reduce inflammation in UC.

Probiotics, Prebiotics, and Synbiotics

Surgery

Indications for urgent surgery

Toxic megacolon refractory to medical management

Fulminant attack refractory to medical management

Uncontrolled colonic bleeding

Indications for elective surgery

Long-term steroid dependence

Dysplasia or adenocarcinoma found on screening biopsy

Disease present 7-10 years

Surgical intervention in IBD includes the following:

UC: Proctocolectomy with ileostomy, total proctocolectomy with ileoanalanastomosis, UC is surgically curable

Fulminant colitis: Surgical procedure of choice is subtotal colectomy with end ileostomy and creation of a Hartmann pouch

CD: Surgery (not curative) most commonly performed in cases of disease complications;

Pouchitis

Patients who undergo the IPAA procedure may develop an idiopathic inflammation termed “pouchitis,”

which typically presents with variable symptoms of increased stool frequency, rectal bleeding, abdominal cramping, rectal urgency, tenesmus, incontinence & fevers.

Patients who develop typical symptoms and signs of pouchitis after the IPAA should be treated with a short course of antibiotics (Evidence A)

Factors influencing disease relapse and remission

The use of NSAIDs and antibiotics

Bacterial and viral infections

Smoking

Psychosocial stress.

Both the severity and extent of disease are important prognostic factors after the first attack of UC.

Thank you

PG Quiz

•Extraintestinal manifestation of IBD are all except?

.1Uveitis

.2Sclerosing cholangitis

.3Osteoarthritis

.4Skin nodules

•Drugs effective in CD are all except

.15 ASA

.2Cyclosporine

.3Steroids

.4Antibiotics

•A 41 yr old male present wit recurrent episodes of bloddy diarrhea for 3 yrs, despite adequate doses of sulfasalzine. He had several exacerbations requiring

steroids to control the flares. What would be the next line of treatment

•Methotrexate

•Azathioprine

•Cyclosporine

•Cyclophosphomide

•Which of the following features is more commonly associated with ulcerative colitis than with Crohn’s disease?

•(A) Fistulas

•(B) Rectal bleeding

•(C) Segmental involvement

•(D) An abdominal mass

•(E) Mesenteric lymph node involvement

A 20-year-old woman with a family history of IBD presents with a history of intermittent right lower quadrant pain and diarrhea. Colonoscopy shows no evidence of rectal involvement but does show aphthous ulcerations in the proximal colon. Of the following serologic markers, which has a 50% likelihood to be elevated in this situation?

1.Anti-goblet cell autoantibody

2.Elevated titre against Entamoeba histolytica

3.Anti-Saccharomyces cerevisiae antibody

4.pANCA