CROHNs DISEASE Definition n Granulomatous inflammatory disease non

CROHN’s DISEASE Definition n Granulomatous inflammatory disease, non specific, producing necrosis and scaring of segments of gastrointestinal tract, which is chronic and develops in recurring episodes : n n n Acute phase (inflammation) = deep ulcers +/- perforations with abscess formation and adhesions to adjacent structures Chronic phase (fibrotic) = stricture formation. Epidemiology n n High incidence in Scandinavia, N-V Europe and N-E of North America Maximum incidence 20 -30 y; More in Caucasians and Jewish population More in women

CROHN’s DISEASE n Ethiology: n n Unknown, probably multifactorial; Potential factors involved: n Genetic: n n n Infectious: n n Sugested by the presence of granuloma There is evidence for: viruses, bacteria and mycobacteria Concomitent infections – E. coli, Clostridia, Campylobacter. Alergies: n n Both twins develop disease; Higher chance for an individual with familial clustering of Crohn’s; Alergens in food and inhaled (fungus, molds) – anamnestic data, alergic testing and more favorable results with specific hyposensitisation Food:

CROHN’s DISEASE n Immunological n Association with: arthritis, eritema nodosum: complex Ag-Ab should be present n Presence of Ab against different Ag structures and increase concentration of Ig. A; n Inflammatory infiltration and epitheliod granuloma formation = high level immune cell mediated reaction against Ag structures; n Corticoids and immune suppresive medication are highly effected in Crohn’s disease; n Probable: immune changes at the level of the mucosa with hyperactive immune response against foreign Ag with cross reaction and nonspecific tisular injury (innocent bystander)

CROHN’s DISEASE

CROHN’s DISEASE n n Pathology: distribution: n n n Terminal ileum and colon 90% of cases; Oro pharinx, esophagus, stomach and duodenum – very rare; Number of lesions n Numerous lesions with normal segments in between ESSENTIAL of diagnostic

n n n Macroscopy Edema, eritema, ulcerations, pseudopolyps, fibrosis, sclerosis Acute phase: bowel n n n edema, enlarged, inflammed (redish), inert friabile; Limits: very clearly delimited Diseased areas are separated by normal segments ; Mesentery n n Edema, infiltrated with lymph node hypertrophy Sometimes more extensive then bowel lesions

CROHN’s DISEASE Presence of ulcer and ulcerations – can be very small or serpent like + transverse ulcers producing the image of islands (cobblestone); n Fissures and ulcers are the origin of fistulas (enteroenteric, entero-colic, entero -cutaneous, entero-vezical, entero-vaginal) n

BOALA CROHN n pseudopolyps

n n Fibrosis, sclerosis, structure formation Bowel wall very thick (up to 1 cm) Structures, short or long, unic or multiple; Advanced stages: on long continuous stenosis

CROHN’s DISEASE n Mycroscopy: characteristic = granuloma with epithelioid giganto cellular cells : n n Giant cells + Langerhans cells + limphocytes (+ plasma cells, eosinophils and PMN); Never caseous necrosis≠tuberculosis; Same inflammation in regional lymphnodes Inflammatory infiltration is found through all strata of the bowel wall;

CROHN’s DISEASE Symptoms n n Insidios onset but mai also be sudden; A. symptoms associtaed with bowel problems n n PAIN n n n DIARHEA n n Dull pain, medium intensity in the RLQ Colicky when associated with obstruction: may be projected in the upper abdomen. 4 -6/day – watery or semisolid Proportional to extent of lesions and activity of disease; Bleeding per rectum: distal lesions. NAUSEA, VOMITING, BORBORISM. B. general symptoms n n n fever 38 0 C, +/- chills Weight loss: diarhhea plus reduced surface for nutrient absorbtion

CROHN’s DISEASE C. extraintestinal Skin n n n „metastatic” ulcers – submamar, subpubian, abdomen; Parastomal ulceration Anal and perianal ulcerations: eritema nodosum; Aftoid oral ulcerations Pyoderma gangrenosum. n n n Joints n Peripheral arthriits n Spondilitis ankilopoetica n Artralgia. Hepatobiliary n n n Sones due to interruption of enterohepatic cycle; Granulomatous hepatitis; Steatosis ; Cholangitis; Fibrosis. n n Stones; Hydronefrosis; Fistula. Ocular n n n Urinary Iridociclitis ; keratitis; conjunctivitis; uveitis Hematological n n n anemia; trombocitosis; limfocitosis – B 12, ferum, folic. acid deficit

CROHN’s DISEASE n Clinical examination n general: malnurishes, pale, cutaneous lesions; abdomen: n n inspection n n palpation n n Pain in the RLQ Guarding: perforative complications; Palpable bowel loop in RLQ, deep, badly delimited, painful. percution n n nothing Regional distension (stenosis); P. O. scars – important postapendectomy. dull ascultation n borborism, sometime. n perineal region n n rectal n n n Perianal fistula; ulcerations; fissure. Often nothing; Sometimes diffuse inflammation. Fistula n n entero-cutaneous visible; entero-vezical n n n disuria, polakiuria pneumofecaluria. recto-vaginal – symptoms and visible on direct examination. in the gallbladder: similar with acute cholecistitis retroperitoneal – diffuse celulitis (very severe but very rare)

CROHN’s DISEASE n Paraclinical n Lab n n anemia – most oftem microcytic, hypochromc but macrocytic anemia can develop (B 12 deficit) leucocitosis n n n In acute phase in complications (absces, fistula) trombocitosis ESR increased; Electrolite embalance due to diarhea

Radiology - barium meal n n Alternation of normal and affected areas Early stages n nonspecific; irregular folds, thickened folds; Ulcers: deep in the wall aspect of rose thorn associating 3 aspects Pseudopolyps; n Small spiculiform lateral ulcerations n Large ulcers ; IRREGULAR COBLESTONE n n Advanced stages n n n No more folds; Rigid stenotic tube Stenosis + distended segments above; Fistulas. particular n n Terminal ileum – rigid cord; Cecum – filling defect on the inner border + retraction.

n Endoscopy GOLD STANDARD n n Small lesions + biopsy + extent of lesions + monitor Rectoscopia: n n n 75% normal; Coblestones aspect Ulcers or stenosis friable mucosa that bleeds on touch. Colonoscopy – similar + ileum!!! Gastroscopy

n Biopsy n n n Others: n n Deep + multiple Even in normal area. Plain abdominal X-ray – in onclusive disease; Bone X-ray for associated bone disease; Fistulography. Laparoscopy

CROHN’s DISEASE Diagnostic: positive n Clinical scenario n n Radilogy n n n segmentary, discontinuous lesions and asymetric lesion; Deep transmural ulcers; „cobblestone”, „string sign”, presence of pseudopolipilor; Stenosis and fistula. Endoscopy n n n Young pt with diarhhea, abdominal pain I RLQ (often) +/- mass on palpation +/- fissure or fistula perianal. . Skip lesions; Multiple ulcers associated with edematous mucosa +/- stenosis Pathology n n epithelio-giganto-celular granuloma; lymphocytes and plasma cells infiltration - suggestive

BOALA CROHN Diferential 1. Ileal disease n n n Acute ileitis Acute apendicitis, apendiceal plastic peritonitis. tuberculosis n n n More general signs and PPD+; Biopsy. Adnexal tumors. Ileal carcinoid tumors: carcinoid syndrome Radiation enteritis n After RXT and diseapears after months.

BOALA CROHN Diferential 2. colonic disease n n Ulcerative colitis Colonic cahnges in laxative abuse n n n n Watery diarrhea in a person that uses laxatives Rx – loss of haustrations and signs of iritable bowel syndrome. Ischemic colitis Diverticulosis Cancer Poliposis IBS

Complications local n n n Abscess formation Fistula Stenosis n n n Inflamatory or scars; Incomplete obstruction GI Bleeding - mostly from colic origin Perforation: free perforation with peritonitis is very unusual. Toxic megacolon – rare but very serious disease n n Toxic status + fever + major abdominal pain + bloody and mucus diarrhea + abdominal distension RX massive distension and destructuring

Complications - general n Extraintestinal may be considered part of the disease or complications if severe n n Cutaneous, joints, liver, small vessels (thromboembolic disease, Takayashu disease Renal n n Neuropsyhic: n n n Urinary lithiasis Obstructions due to mechanical compression of urethers; Sciesures or tetany due to hypo. C and hypo. Mg Anorexia Psihosis. Malabrobtion with consequences on growth. Amiloidosis (visceral and renal) – after 10 years of evolution Endocrine: n amenoreea, infertility, late puberty

Medical n General TREATMENT Bed rest Psihoterapy; Dietary n n n hypercaloric, hperproteic, vitamines (folic, A, D, K, C, B 12) and minerals (Ca++, Mg++, K+, Fe++, Zn++); EXCLUDE: n n n Food with many fibers )mostly in pt with stenosis; Milk – intolerance ; Lipids in case of malabsorbtion of lipids. n Symptomatic n n Pain therapy Treat diarrhea: n n codeine phosphat Treat dep on cause: n n n No spices ; No milk - intolerance; Bile salts: interruption of the liver-enteric cycle; Atb - infection Treat electrolytic imbalance. Traet anemia : Fe, B 12, folic acid

TREATMENT - pathogenic ANTIINFLAMMATORY n n n 5 ASA Salazopirine: better in colonic disease ANTIBIOTICS n n n Metronidazol. ; Chinolone CORTICOIDS - may induce remission IMMUNE SUPRESSION n n n Azatioprina (Imuran) – prevention of recurrence; 6 mercaptopurine Cyclosporine Methotrexat

TREATMENT n SURGICAL n Indications Acute complications n local complications – stenosis, fistula; n Unclear diagnostic. n Limited resection of involved bowel n Enterostomy – end later resection n

TREATMENT n n A. Crohn ileocolic Indications: n n n fistula; obstruction; ; Percutaneous drainage and resections

n n B. Colonic Crohn Indication n TREATMENT same; megacolon toxic. 3 operaţii: n n n proctocolectomy (abdomino-perineal) with permanent ileostomy; Total colectomy and ileostomy but rectum in place; Total colectomy plus ileorectal anastomosis.

n n n TREATMENT Anal and perianal Treatment of the abscess and fistula + treatment of Crohns. If refractory disease n the rectum - proctectomy

n Obstruction n ileon: n n TREATMENT Ileon resection; Ileo-cecal resection By pass. colon: n n by-pass; Ileostomy or colostomy.

n Stenosis n n TREATMENT rezections Stricture-plasty

n Long term complication Cancer n n n High risk for pt with long term Crohns, strictures and scleroiss cholangitis Colonoscopic monitoring – 2 -3 y Displastic lesions: colectomy

ULCERATIVE COLITIS n Ethiology n n n unknown More frequent USA, England, northern countries; Onset 18 -30 y n n n Under 18 very severe; Over 50 very unusual. More often in male pt

n Genetic factors n n n Numerous germs isolated but not clear; Atb not very good; Probably secondary and cause of recurrence. Enzimatic n n n Family clustering; Possible implication of a defect in Ig. A production Infection n n UC Increased synthesis of lizozim – destroys the protective mucus; Not clear if primary or secundary. Psihosomatic n n Patients are more psichologically vulnerable to conflict; Emotional problems involved in onset and maintenance of new episodes

n Pathology n Macroscopy serosa n n n Reddish and glittering; Pale or pale with red spots. n n Shortening of the length; Narrow lumen; No haustrations; Thick wall (due to the muscle layer); Friable, paper-like. mesocolon n normal. advanced n n n retracted; Large lymph nodes. Sometimes psudopolyps Patches of renewed musosa near the lesions Intense renewal – mucosal bridges and vegetations chronic initially n n red Small erosions – ulcers (superficial. Not deep); brittle; Continuous lesions Wieschelmann pseudiopolyps subacute: n Very dilated bowel. Severe n n n Fulminant disease n n n Distended, thin; Advanced n n n Initially: n n Acute: n Intestinal wall n n n chronic n n mucosa: Acute n n Wide spread lesions with incomplete healing of the mucosa; Thin mucosa; UC

n UC Particular aspects – affects only the mucosa of the rectum and the colon n First rectum then colon The lower the segment the more aggressive the disease; The lesions are continuous;

UC n Microscopy: n n Dilation of vessels folllowed by haemmorhage; limfocites and plasmocites; Deep glands are full of neutrophils – abcess of the crypts – ulcerations and pseudopolips. histology: n n Granulocyte infiltration is specific If inflammation spreads to all layers – toxic megacolon.

n n UC Clinic digestive symptoms n diarrhea: n n n First in 30 -50% cases; Main symptom 4/5; Feces in a sero-hematic liquid full of puss 2 -3 up to 15 -20 stools/day; Sometimes just blood per anum Abd pain: n n Colicky – left side characteristic: n n n tenesmus; No more pain after a stool is passed. General n n Fever –septic; Weight loss; Vomiting; Tachycardia - depending on amount of lost fluids.

n Clinical exam n abdomen: n inspection: n n reduction of subcutaneous tissue; bloating - especially supraumbilical - installation may highlight acute toxic dilatation of the colon. percution: n n n UC timpanism increased in the case of toxic dilatation of the colon; painful; auscultation: multiple air-liquid noises uncomplicated ulcerative colitis tranquility in ulcerative colitis complicated by megacolon. Rectal exam n n n sphincter tone: increased due to pain; decreased in severe forms; rectal wall: rigid; granular mucosa; stricture areas; Mucosa: endoscopy inflammatory exudate in the rectal mucosa, or the presence of blood, mucus, pus; highlights other injuries: cancer, hemorrhoids, abscesses, fistulas, etc. .

UC n stool: n n in severe forms, extensive: stools are unformed, with feces floating in a serous fluid, blood mixed with mucus and pus; bulky stools with much blood. in mild forms stool can be formed with blood and mucus; in forms limited to the rectum: stools, wrapped in blood and mucus; emissions of blood and mucus without stool. n general: n n n apathy or restlessness, anxiety; palor; dehydration, malnutrition; detection of systemic events: eye; articulation; skin.

UC n Laboratory: leukocytosis - active phases; n anemia; n hypoalbuminemia; n electrolytes: significant changes only in severe forms; lowering of Na +, K +, Cl-, Mg + +; n

n Radiology n UC Simple x-ray or radioscopy n Always first (perforation, incontinence) n Active phase: n n No haustrations; Thick wall; Cobblestone aspect – psudopolyps; Distended lumen;

UC Late, advanced stages n mucosal relief is deleted; n haustations disappear completely; n size is reduced; n linear shape; n distensibility is greatly reduced; n angles rounded; n sometimes stenosis; n rigid tube (microcolia).

Endoscopy Inititial stages: n n n n Ulcerations that may converge with one-another; Crypt abscesses; False membranes. Late stages: n n Red mucosa with vessels visible; Friable mucosa; Bleeding is spontaneous and difuse; Grainy aspect; Blood, mucus and pus in the lumen; Florid stages: n n UC Atrophy of the mucosa; Lack of haustrations; Pseudopolyps; biopsy: Exfoliative cytology

n CT, MRI UC

UC Local complications n May appear in acute UC n n n Perforation Acute dilation Massive bleeding (more than 3000 ml in 24 hours Perianal lessions Due to chronic disease n n n Stenosis of the rectum and colon Pseudopoliposis Cancer

UC general complications n articular n n most frequently; 5 categories: n n n n Rheumatoid arthritis; Spondilitis; Erythema nodosum; Joint pain; Acute toxic arteritis Spondilitis is the only one that can persist after surgery and medical treatment. ophtalmologic n conjunctivitis; uveitis; iritis; episcleritis; keratitis; retinitis. n cutaneous and mucous: n cutaneous n n n Erythema nodosum; pyoderma gangrenosum; Urticaria, acnea, dermatitis. mucous – stomatitis; liver – chronic liver disease and cirrhosis; Kidney - stones, hidronefrosis

UC n Diferential n n n n n Crohn’s disease Colorectal cancer Diseneteria Ischemic colitis Polyposis Bacilarry colitis Irritable bowel syndrome Diverticulosis Piles

UC Treatment n Objectives: n Reduce the time that the patient spends in acute stages of the disease. n Prevent relapses and complications; n n A. Treatment of the acute stage 1. bed rest n 2. food intake n n 3 -5 days of a colon sparing diet n Small, frequent meals; n No milk 3. psihotherapy n 4. correct nutritional and hydroelectrolitical imbalances. n

n 5. antiinflammatories and antibiotics n a) salazopirin b) 5 -aminosalicilic acid c) corticoids and ACTH d) antibiotics n n n fever; sepsis. e) immunosuppressive treatment n n n 6 -mercaptopurin; 6 -tioguanin; Azatioprin Metrotrexate Ciclosporin

UC n B. Prevent relapse n 1. Salazopirin n 1, 5 -2 g/day 6 -9 months; n 2 -2, 5 g/day 10 days/month. 2. diet. n 3. avoid psychological stress, respiratory or digestive tract infections; n 4. follow up. n

n C. Surgery n n 1. total proctocolectomy and permanent ileostomy 2. total colectomy, treatment of the rectal stump and reestablishment of the continuity of the digestive tract 6 -12 months later n n n Risc of a disease progression or relapse Cancer risk. 3. total colectomy with ileorectal anastomosis in the same procedure;

Diverticular disease n Definition n n Herniation of the colic mucosa through defects of the muscle layers Frequency n n n Incresed with aging: Sex: ♂: ♀ = 2: 1; Incidence: n n n Maximal in Western Europe Minimal în Africa and Asia. More frequent in urban patients and in patients with stressfull jobs.

Diverticular disease n Aethiology n Precise cause is unknown. Development of diverticulae: n n Muscle contraction: n n Hipertrophy of the circular musculature Shortening of longitudinal fibers; The result is pressure pockets that push the mucosa throus the muscle fibers Weak spots in the colonic wall

Diverticular disease n n Weakening of the wall due to fatty inflammation; Low fiber intake - constipation; Psychological stress; In time: n n Stasis of feces – fecaliths – ulcerations of the mucosa due to mechanical irritation – increase in septic fenomenae. Closed cavity – increase in virulence of germs and increase in mucus secretion – congestion – inflammation – thickening of the wall

Pathology n n Number – rarely unique: Topography: n Entire colon: n n n Structure: n n n Most frequent on descending and sigmoid; Rectum is not affected. Body and sometimes also a neck !False diverticulae! Colon: n n n Shortened and thickened teniae; Arches of circular musculature between diverticulae; Normal nercous plexuses.

n Diagnosis n Clinical: Asimptomatic Atypical digestive symptoms: Symptoms usually due to complications. Paraclinical: Barium enema, colonoscopy n n n

n Complications n A. Diverticulitis n 30% of patients with diverticular disease ; n n simptoms: n n n One or more diverticulae Due to stasis of feces peridiverticulitis Very painful – left iliac fosa; Irregular bowel habits; Bloating; Nausea; Fever; Clinical exam: n n Tumor mass in left iliac fosa painful; Lower limit of tumor can be assessed on rectal digital exam Above the tumor the descending colon is short and rigid

n CT, US

Diverticular disease B. Haemmorhage n n Frequent due to vecinity of vessels ; More frequent in the right colon; clinical: n n Large haemmorhage; Rarely melena; Reocurring frequently. paraclinical: n n scintigraphy arteriography: pancolonoscopy laparotomy.

C. Fistulae - due to an n abscess: n exterior: n n interiore: n n n colo-cutaneous colo-enteric, colo-colic colo-uretheral colo-vesical colo-uterine: colo-vaginal 3 syndroms: n n n General septic; Pericolic abscess; Peritonitis

n D. Perforation n n First a pericolic abscess and then peritonitis E. Obstruction n n Mechanical - due to inflammation clinical: n n n Suboclusive syndrom Low obstruction + fever: Tumor mass in the left iliac fossa Barium enema; Colonoscopy + biopsy.

n Medical TREATMENT n Profilaxis of complications: n Avoid constipation; n No spices; n Mild antispastics; n diverticulitis n High fiber intake and laxatives; n Antiinflammatory drugs n Antibiotics.

Surgery n n Segmental resection of affected colon; In emergency – 2 step procedure: n n Hartmann I followed by reestablishment of continuity Colostomy in emergency followed by resection with anastomosis after acute fase passes.