Inflammatory Bowel Disease Flashcards
VEOIBD and infantile IBD mainly affect the colon, are resistant to standard medications, and patients often have a strong family history of IBD, with at least one first-degree related affected.
Very early onset IBD (VEOIBD) has been defined as IBD that occurs in children <6 years of age and infantile IBD in children <2 years old
Consensus hypothesis
3 major host compartments Act together as supra organism 1. Microbiota 2.IEC’s 3. Immune cells
Greatest incidence of IBD: among white and Jewish people but the incidence of IBD in Hispanic and Asian people is increasing, as noted above.
- urban areas have a higher prevalence of IBD than rural areas
- high socioeconomic classes have higher prevalence than low socioeconomic classes.
- smoking: is an important risk factor in IBD with opposite effects on UC and CD whereas in other ethic groups with genetic susceptibility smoking may play a role
Ulcerative Colitis
Epidemiology of IBD Incidence: 0-19.2 per 100000 Age of onset: second to 4th decades and seventh to ninth decade Female/male ratio: 0.51-1.58 Smoking: MAY PREVENT DISEASE Oral contraceptive: no increased risk Appendectomy: PROTECTIVE Monozygotic twins: 6-18% concordance Dizygotic twins: 0-2% Antibiotic use in the first year of life
Crohn’s Disease
2nd-4th decade of life 0.34-1.65 Smoking: may cause disease Oral contraceptives: hazard ratio 2.82 Appendectomy: not protective Monozygotic twins: 38-58% Dizygotic twins: 4% concordance
Etiology and pathogenesis
-a consensus hypothesis is that each of these three major host compartments that function together as an integrated “supraorganism” (micobiota,IECs, an immune cells within (smoking,antibiotics,enteropathogens) and genetic factors
IBD considered n inappropriate immune response to the endogenous (autochthonous) commensalism microbiota within the intestines with or without some component o autoimmunity.
Genetic considerations
Genetic underpinning of IBD in early life
These include mutations in genes encoding, for example, interleukin-10 (IL-10), the IL-10 receptor (IL-10R), cytotoxic T-lymphocyte associated protein-4 (CTLA4), neutrophil cytosolic factor 2 protein (NCF2), X-linked inhibi-tor of apoptosis protein (XIAP), lipopolysaccharide responsive and beige-like anchor protein (LRBA), or tetratricopeptide repeat domain 7A protein (TTC7), among many other genes that are involved in host-commensal interactions.
Commensal microbiota and IBD
-biomass of ~1012 colony-forming units per gram of feces is achieved by 3 years of age
the microbiota, through its structural components and metabolic activity, has major influences on the epithelial and immune function of the host, which, through epigenetic effects, may have durable consequences.
-UC and CD demonstrably differerent from non afflicted individual
State of dysbiosis: suggesting the presence of microorganisms that drive disease
Proteobacteria: enteroinvasive and
Adherent escherechial coli: immune response is directed and or the loss of microorganisms that hinder inflammation ( e.g firmicutes such as faecalibacterium prausnitzii)
Defective immune regulation in IBD
-mucosal immune system does not normally elicit an inflammatory immune response to luminal contents due to oral (mucosa) tolerance.
- oral tolerance may be responsible for the lack of immune responsiveness to dietary antigens and commensal microbiota.
- in IBD this suppression of inflammmation is altered, leading to uncontrolled inflammation known.
- intestinal inflammation in these animal models requires the presence of commensal microbiota
Inflammatory cascade in IBD
Inflammatory cytokines from innate immune cells such as IL-1, IL-6, and TNF have diverse effects on tissues.
-promote fibrogenesis, collagen production, activation of tissue metalloproteineses, and the production of other inflammation mediator, they also activate the coagulation cascade in local blood vessels
TH1 cells (secrete interferon (IFN y)
- induce granulomatous inflammation that resembles CD
- initiated by IL-12
TH2 cells( secrete IL4, IL5, IL3)- and related NK T cells that IL4,IL5, and IL13 induce superficial mucosal inflammation resembling UC -Induced by IL4, IL 23 with IL13
TH17 cells (secrete IL17, IL21)
— cells may however also provide protective functions.
- for neutrophilic recruitment
-induce by TGFB
Innate immune-like cells that lack T-cell receptors are also present in intestine, polarised to the same functional fates and may similarly participate in IBD
Neutralization of the cytokines by IFNy or IL17
IL23: inhibits the suppressive function of regulatory T cells
Activated macrophage: secrets TNF and IL6
Pathology
UC: mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon
30-40% have disease extending beyon the sigmoid
20%-total colitis
backwash ileitis: inflammation extends 2-3 cm into the terminal ileum in 10-20%
MILD
Eryhtematous and has fine granular surfac that resembles sand paper.
SEVERE:
Mucosa is haemorrhaging edematous and ulcerated
Inflammatory polyps: pseudo polyps
Toxic colitis or mega colon: fulminant disease
Ulcerative colitis: microscopic features
-limited to the mucosa and superficial submucosa
First, the crypt architecture of the colon is distorted; crypts may be bifid and reduced in number, often with a gap between the crypt bases and the muscularis mucosae.
Second, some patients have basal plasma cells and multiple basal lymphoid aggregates. Mucosal vascular congestion, with edema and focal hemorrhage, and an inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells, and macrophages may be present. The neutrophils invade the epithelium, usually in the crypts, giving rise to cryptitis and, ultimately, to crypt abscesses
Crohn’s disease:
macroscopic features
affect any part of the gastrointestinal (GI) tract from the mouth to the anus.
30-40%: have small bowel disease alone
40-55%: involve small and large intestine
15-25%: colitis alone
(RECTUM IS SPARED)
SKIP LESIONS
Perirectal fistulas, fissures, abscesses anadromous anal stensis present in 1/3rd
CD may involved the liver and pancreas
TRANSMURAL PROCESS
Aphthous ulcer or superficial ulceration: mild disease
COBBLESTONE
Pseudopolyps can also form
ACTIVE CD: focal inflammation and formation of fistula tracts, which involves fibrosis and strricturing of the bowel
Creeping fat: projections of thickened mesentery inflammatory promotes adhesions and fistula formation
Crohn’s disease: microscopic features
Earliest: aphthoid ulceration and focal crypt abscess with loose aggregations of macrophages: non caseating granulomas.
Granulomas: characteristics of CD
Histology:
Submucosal or subserosal lymphoid aggregates
Ulceration gross and microscopic skip areas and transmural inflammation accompanied by fissures that penetrate deeply into the bowel wall and sometimes form fistulous tracts or local abscesses.
CLINICAL PRESENTATION
-ulcerative colitis:
Signs and symptoms:
major symptoms of UC are diarrhea, rectal bleeding, tense up, passage of mucus and cramps abdominal pain
- symptoms should be weeks or months
- proctitis: usually pass fresh blood or blood-stained mucus, either mixed with stool or streaked onto the surface of a normal or hard stool
- tenesmus, urgency with a feeling of incomplete evacuation, but rarely have abdominal pain
Severe: pass a liquid stool containing blood,pus and fecal matter
- diarrea is open nocturnal and or postprandial
- severe pain is not a prominent symptoms
- severe cramping and abdominal pain can occur with severe attacks of the disease
- symptoms of moderate to severe: anorexia, nausea,vomiting, fever, and weight loss.
Laboratory, endoscopic and radiographic features
rise in acute-phase reactants (C-reactive protein [CRP]), platelet count, and erythrocyte sedimentation rate (ESR), and a decrease in hemoglobin
Fecal lactoferrin:
a glycoprotein present in activated neutrophils, is a highly sensitive and specific marker for detecting intestinal inflammation.
Fecal calprotectin;
is present in neutrophils and monocytes and levels correlate well with histologic inflammation, predict relapses, and detect pouchitis.
Sigmoidoscopy: used to assess disease activity and is usually performed before the treatment
Colonoscopy: is used to asses disease extent and activity in patients not in acute flare
Endoscopically mild disease is characterized by erythema, decreased vascular pattern, and mild friability.
Moderate disease is characterized by marked erythema, absent vascular pattern, friability and erosions, and severe disease by spontaneous bleeding and ulcerations
Complications: only 15% of patient with UC present initially with catastrophic illness.
Massive hemorrhage occurs with severe attacks of disease in 1% of patients, and treatment for the disease usually stops the bleeding.
However, if a patient requires 6–8 units of blood within 24–48 h, colectomy is indicated
Toxic megacolon is defined as a transverse or right colon with a diameter of >6 cm, with loss of haustration in patients with severe attacks of UC.
Perforation: most dangerous of the local complications
-perforation is rare
Complicating a toxic megacolon about 15%
Cancer: always consider with UC
Stricture in 5-10%
UC
1. Patient occasionally develop anal fissure, perinanal absceses, haemorrhoids extensive perinatal lesions should suggest CD
CROHN’S Disease
Signs and symptoms
-2 patterns of disease
: fibrostenotic obstructing pattern
: penetrating fistulos pattern
Ileocolitis:
Must common site of inflammation: terminal ileum
-presenting as: right lower quadrant pain and diarrhoea
—right lower quadrant pain, a palpable mass, fever and leucocytosis
— pain is usually colicky: precedes and relieved by defecation
—low spiking fever: usually
— high grade fever suggest intraabdominal abscess formation
—weight loss is common 10-20%
Diarrhoea, anorexia and fear of eating
—inflammatory mass: palpated in the right lower quadrant of the abdomen
—may obstruct the right urethras or blazer inflammation
—string sign: severely narrowed loop of the bowel which makes the lumen resemble a frayed cotton string
Incomplete filling: as a result edema, irritability and spasms associated with inflammation and ulceration
-early stages; bowel wall edema and spasm produce intermittent obstruction, increasing post prandial pain
—severe inflammation of the ieocecal region may lead to localised wall thinning, with microperforation and fistula formation to the adjacent bowel , the skin or the urinary bladder.
—enterovescical
—enterovaginal fistula
Jejunoileitis
—extensive inflammatory disease:loss of digestive and absorptivesurface resulting in mal absorption and steatorrhea
Intestinal malabsorption: cause anemia, hypoalbuminemia,hypomagnesemia,coagulopathy, and hyperoxaluria with nephrolithiasis
Vertebral fractures: vit D, hypocalcemia, prolonged glucocorticoid use.
Pellagra from niacin deficiency can occur in extensive small-bowel disease, and malabsorption of vitamin B12 can lead to megaloblastic anemia and neurologic symptoms.
- vitamin A,E and K
- zinc, selenium, copper and magnesium
Diarrhoea: characteristics of active disease
1) bacterial overgrowth in obstructive stasis or fistulization
2) bile—acid malabsorption due to diseased or resected terminal ileum
3. Intestinal inflammation with decreased water absorption
Crohn’s:
Colitis and perianal disease
>low grade fever, malaise, diarrhoea, cramps abdominal pain, and sometime hematochezia.
Stricturing can occur in the colon in 4–16% of patients and produce symptoms of bowel obstruction.
- endoscopic is unable to traverse a stricture in Crohn’s disease
- perianal disease affects Crohn’s colitis and is manifested by incontince, large hemorrhoidal tags, anal. Strictures , anorectal fistulae and periirectal abscess.
Crohn’s:
Gastronome also disease
- nause, vomiting, epigastric pain
- second portion of the duodenum : more commonly involved than the bulb
Crohn’s: laboratory, endoscopic and radiographic features
-elevated ear, and carp
Severe cases: hypoalbuminemia, anemia, leukocytosis
CD: rectal sparing, aphthous ulcer, fistulas, skip lesions
Strictures ≤4 cm in length and those at anastomotic sites respond better to endoscopic dilation.
The perforation rate is as high as 10%. Most endoscopists dilate only fibrotic strictures and not those associated with active inflammation
Wireless capsule endoscopy (WCE) allows direct visualisation of the entire small bowel mucosa: higher CT or MRI or small bowel series
CD patency capsule, which is made of barium and starts to dissolve 30h after ingestion
-abdominal X-ray can be taken around 30h after ingestion to see if the capsule is still present in the small bowel, whic would indicate a stricture
—early radiologic finding: thickened folds and aphthous ulceration
: cobblestoning from longitudinal and transverse ulceration most frequently involves the small bowel
Advanced: fistulas, inflammatory masses, and abscesses may be detected.
Earliest macroscopic findings: colonic CD are aphthous ulcers
TRANSMURAL inflammation: CD leads to decreased luminal diameter and limited distensibility.
CT enterography (CTE) and MR enterography (MRE) and small-bowel follow-though (SBFT) have been shown to be equally accurate in the identification of active small-bowel inflammation, CTE and MRE have been shown to be superior to SBFT in the detection of exraluminal complications, including fistulas, sinus tracts, and abscesses.
MRI: is though to Ofer superior soft tissue contrast and has been added to the advantage of avoiding radiation exposure changes.
Pelvic MRI : is superior to demonstrate ischiorectal abscesses an perianal fistula.
Crohn’s complications
CD is a transmural process
-risk for fistula formation and reduce the incidence of free perforation
- ileum: where perforation usually occurs but occasionally in the jejunum or as complication to toxic megacolon
- peritonitis of free perforation especially colonic, may be fatal
- CT-guided percutaneous drainage of the abscess: standard of therapy
Systemic glucocorticoid: increase the risk for intraabdominal and pelvic abscesses in the CD patients who had never had an operation.
complications include intestinal >obstruction in 40%,
>massive hemorrhage,
>malabsorption,
>and severe perianal disease.
Serologic markers in CD:
-the potential risks of biological therapies such as infection and malignancy, and it would be optimal to determine by genetic or serologic marker at the time of diagnosis which patients will require more aggressive medical therapy.
whereas increased levels of perinuclear antineutrophil cytoplasmic antibodies (pANCA) are more commonly seen in patients with UC.
Increased titers of anti-Saccharomyces cerevisiae antibodies (ASCAs) have been associated with CD
These serologic markers tend to have low sensitivity and specificity though due to elevation in levels cause by other autoimmune diseases, infections and inflammation outside the GI tract.
Differential diagnosis of UC and CD
-INDERTERMINATE COLITIS: impossible identity between UC and CD
- Infectious disease: (bacterial, fungal, viral, protozoan orgin)
Campylobacter colitis can mimic the endoscopic appearance of severe UC and can cause a relapse of established UC.
Salmonella can cause watery or bloody diarrhea, nausea, and vomiting.
Shigellosis causes watery diarrhea, abdominal pain, and fever followed by rectal tenesmus and by the passage of blood and mucus per rectum
Yersinia enterocolitica infection occurs mainly in the terminal ileum and causes mucosal ulceration, neutrophil invasion, and thickening of the ileal wall.
bacterial infections that may mimic IBD include C. difficile, which presents with watery diarrhea, tenesmus, nausea, and vomiting; and E. coli, three categories of which can cause colitis.
These are enterohemorrhagic, enteroinvasive, and enteroadherent E. coli, all of which can cause bloody diarrhea and abdominal tenderness.
Diagnosis of bacterial colitis is made by sending stool specimens for bacterial culture and C. difficile toxin analysis. Gonorrhea, Chlamydia, and syphilis can also cause proctitis.
Mycobacterium Adium-intracellulare complex: HIV infection and other immunocompromised states
diarrhea, abdominal pain, weight loss, fever, and malabsorption.
Diagnosis is established by acid-fast smear and culture of mucosal biopsies.
CMV occurs most commonly in the esophagus, colon, and rectum but may also involve the small intestine.
CMV occurs most commonly in the esophagus, colon, and rectum but may also involve the small intestine.
abdominal pain, bloody diarrhea, fever, and weight loss. With severe disease, necrosis and perforation can occur.
Dx; Diagnosis is made by identification of characteristic intranuclear inclusions in mucosal cells on biopsy
Herpes simplex infection of the GI tract is limited to the oropharynx, anorectum, and perianal areas. Symptoms include anorectal pain, tenesmus, constipation, inguinal adenopathy, difficulty with urinary voiding, and sacral paresthesias. Diagnosis is made by rectal biopsy with identification of characteristic cellular inclusions and viral culture.
HIV itself can cause diarrhea, nausea, vomiting, and anorexia. Small intestinal biopsies show partial villous atrophy; small bowel bacterial overgrowth and fat malabsorp-tion may also be noted.
Protozoan parasites include Isospora belli, which can cause a self- limited infection in healthy hosts but causes a chronic profuse, watery diarrhea, and weight loss in AIDS patients.
Entamoeba histolytica or related species infect about 10% of the world’s population; symptoms include abdominal pain, tenesmus, frequent loose stools containing blood and mucus, and abdominal tenderness. Colonoscopy reveals focal punctate ulcers with normal intervening mucosa; diagnosis is made by biopsy or serum amebic antibodies. Fulminant amebic colitis is rare but has a mortality rate of >50%.
parasitic infections that may mimic IBD include hookworm (Necator americanus), whipworm (Trichuris trichiura), and Strongyloides stercoralis
severely immunocompromised patients, Candida or Aspergillus can be identified in the submucosa. Disseminated histoplasmosis can involve the ileocecal area.
Parasitic infections that mimic IBD include
Hookworm(negatory americanus)
Whip worm: trichuris trichiura and stronglyloides stercoralis
In immunocompromised: candida or aspergillosis can be identified in the submucosa
Disseminated histoplasmosis: involve oleo Cecal area
