Moving beyond the horizon of inflammatory bowel … · Chronic colitis Moving beyond the horizon of inflammatory bowel disease Sanjay Kakar, MD UCSF
Post on 30-Apr-2018
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Chronic colitis• Clinical
Acute: symptoms < 1 month Subacute/chronic 1-6 monthsChronic >6 months
• HistologicalArchitectural distortionIncreased lamina propria inflammationPaneth cell metaplasia
Colitis: patterns
NONCRYPT DESTRUCTIVELymphocytic/collagenous colitis Nonspecific ulcer GranulomatousEosinophilic colitis
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Approach to diagnosis
• Pattern-crypt destructive/nondestructive-histological categories based onadditional features
• Etiologic diagnosis-clinical and endoscopic findings-suggested work-up to establish etiology
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Diverticular disease-associated colitis
• Mild inflammatory changes around ostia• Mucosal prolapse• IBD-like changes
Mimic Crohn disease and ulcerative colitis
Diverticular disease-associated colitis
Distinction from ulcerative colitis• Segmental disease limited to sigmoid
colon• Rectal involvement favors UC
Diverticular disease-associated colitis
Distinction from Crohn disease• Ileocecal disease or anal fissures/fistulae
favor Crohn disease • Segmental disease limited to sigmoid
colon
Diverticular disease-associated colitis
Distinction from Crohn diseaseGoldstein, AJCP 1997
• 25 patients with diverticulosis and histological features of Crohn disease limited to sigmoid colon
• 23/25 patients did not develop Crohndisease on follow-up
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Diversion colitis
• Obstructive disease of sigmoid or rectum: carcinoma, diverticulitis, Crohn disease
• Defunctioned rectum in UC during 3-stage pouch procedure
Diversion colitis
• Florid lymphoid hyperplasia• IBD-like features: architectural distortion,
ulceration, crypt inflammation• Diverted segments in Crohn disease
resemble ulcerative colitis• Diverted segments in ulcerative colitis
resemble Crohn disease
Diversion colitis
Role of the pathologist• Clinical information necessary for
distinction from IBD• Diagnosis of Crohn or UC should never
be changed based on findings in diverted segment alone
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Ileoanal pouch
Adaptive changes• Mild inflammation, variable villous
atrophy : 50%• Intermittent increase in inflammation with
recovery: 30-40%• Complete atrophy with active
inflammation: 10-20%
Chronic pouchitis
• Clinical, endoscopic and pathologic features
• Clinical: Diarrhea, pain, urgency, discharge
• Endoscopic: Diffuse process with contact bleeding, ulcers
Chronic pouchitis
Pathologic features• Active chronic inflammation• Villous atrophy• Superficial ulcers• Fissures and fistulae uncommon• Granulomas
Chronic pouchitis
Role of the pathologist• Diagnosis of pouchitis
-integration of clinical and endoscopic data -diffuse process -localized: ischemia, mucosal prolapse, inflammatory polyps
• Is it Crohn disease?
Chronic pouchitis
Is it Crohn disease?• Granulomas, pseudopyloric metaplasia
can occur in pouchitis• Deep ulcers uncommon in pouchitis• Diagnosis never changed to Crohn
disease based on findings in pouch mucosa alone
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Infectious colitis
• Pattern of acute colitis• Self-limited/ infectious-type/
nonrelapsing colitis• Some infections:
Histological picture of chronic colitis that can mimic IBD
Infectious colitis with IBD-pattern
• Bacterial: Salmonella, ShigellaAeromonasYersinia, MycobacteriaActinomyces
• Viral: Cytomegalovirus• Parasitic: Entameba
Yersiniosis
• Granulomatous enterocolitisresembling Crohn disease
Fissuring ulcers, transmuralinflammation, granulomas
• DiagnosisCultures, serological studiesPCR from paraffin-embedded tissue
Yersiniosis vs Crohn disease
Favor Yersinia• Short duration of symptoms• Suppurative granulomasFavor Crohn disease• Prominent architectural distortion• Duplication of MM, neural hyperplasia
Ileocecal tuberculosis
• Ileocecal granulomatous disease• Ulcers and strictures• Clinical data (pulmonary disease)
AFB stain/culture/PCR assay
TB vs. Crohn diseaseFavor tuberculosis• Larger, confluent, necrotizing granulomas• Transverse ulcers• Ulcers lined by histiocytes, prominent
submucosal inflammationFavor Crohn disease• Longitudinal ulcers, fissuring ulcers, fistulae• Transmural lymphoid aggregates
Infectious colitis with IBD-pattern
• Bacterial: Salmonella, ShigellaAeromonasYersinia, MycobacteriaActinomyces
• Viral: Cytomegalovirus• Parasitic: Entameba
Actinomycosis
• Suppurative and granulomatous disease • Ileocecal and perianal regions• Fistulae mimicking Crohn disease
Sinuses mimicking abscessMass lesion mimicking carcinoma
Infectious colitis with IBD-pattern
• Bacterial: Salmonella, ShigellaAeromonasYersinia, MycobacteriaActinomyces
• Viral: Cytomegalovirus• Parasitic: Entameba
CMV colitis
• Segmental colitis• Linear ulcers; necrosis and exuberant
granulation tissue• Diagnosis:
Viral inclusionsCMV antigen testSerology, cultures
Infectious colitis with IBD-pattern
• Bacterial: Salmonella, ShigellaAeromonasYersinia, MycobacteriaActinomyces
• Viral: Cytomegalovirus• Parasitic: Entameba
Amebic colitis
• Cecum-most common• Rectosigmoid and diffuse colonic disease• Diagnosis:
History of travel Right-sided diseaseIdentification of trophozoites
Colitis: patterns• NONCRYPT DESTRUCTIVE• CRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiverticular diseaseDiversion colitisPouchitisCertain infectionsDrugs, chronic ischemia/radiation
Drugs: chronic colitis
• Mycophenolate mofetilApoptosis resembling GVHDArchitectural distortion resembling IBD
• NSAIDs, potassium chlorideUlcers and segmental inflammation Architectural distortion typically absent
Colitis: patternsCRYPT DESTRUCTIVE
Inflammatory bowel diseaseDiversion colitisPouchitisDiverticular diseaseCertain infectionsChronic ischemia/radiation
Colitis: patterns
NONCRYPT DESTRUCTIVENonspecific ulcerGranulomatous colitisEosinophilic colitis Lymphocytic/collagenous colitis
Nonspecific (“idiopathic”) ulcer
Typical features are absent• Crohn disease (fissuring, granulomas,
pseudopyloric metaplasia)• CMV: inclusions• Ischemia, pseudomembranous colitis
Nonspecific ulcer
Role of the pathologist• Recognizable patterns of colitis:
ischemic, pseudomembranous, CMV, Crohn
• Guidance to establish the etiology
Nonspecific (“idiopathic”) ulcer• Iatrogenic
Drugs like NSAIDs, KClRadiation
• Infections• Obstructive colitis/ Stercoral ulcers• Systemic disorders
Vasculitis: Behcet syndromeRenal failure
NSAID-related colitis
• 10% of new colitis cases • Nonspecific ulcers: circumferential
pauci-inflammatory• Perforation and hemorrhage
NSAID-related colitis
• StricturesCircumferential, right colonSubmucosal fibrosis
• Endoscopy‘Diaphragm-like’ or membranous
strictures in R colon
NSAID-related colitis
• Segmental involvement with acute or focal active colitis
• Acute ischemic colitis• Exacerbation of pre-existing disease:
diverticulitis, IBD• Lymphocytic/collagenous colitis
NSAID-related colitis
Role of the pathologist• Raise the possibility of NSAIDs with
different histological patterns• Most resolve on discontinuation of the
drug
Nonspecific (“idiopathic”) ulcer• Iatrogenic
Drugs like NSAIDs, KClRadiation
• InfectionsYersinia, Campylobacter
• Obstructive colitis/ Stercoral ulcers• Systemic disorders
Vasculitis: Behcet syndromeRenal failure
Obstructive colitis
• Ulceration proximal to site of obstruction• More active inflammation than NSAIDs• Stercoral ulcers:
Pressure effects on colonic mucosa by inspissated feces
Nonspecific (“idiopathic”) ulcer• Iatrogenic
Drugs like NSAIDs, KClRadiation
• Infections• Obstructive colitis/ Stercoral ulcers• Systemic disorders
Renal failure Vasculitis: Behcet syndrome
Behcet syndrome
• Ileocecal and anorectal ulcers• Typical features of Crohn disease absent • Triad of oral ulcers, genital ulcers and
uveitis• Cutaneous involvement, arthritis
Colitis: patterns
NONCRYPT DESTRUCTIVENonspecific ulcer Granulomatous colitisEosinophilic colitis Lymphocytic/collagenous colitis
Granulomas in Crohn disease
• Small mucosal granulomas are nonspecific• Well-formed granulomas away from
inflammation, basal mucosa or submucosa• Young patients, early phase, distal
locations
Granulomatous colitis
• Crohn disease• Infections: yersiniosis, tuberculosis,
fungal infections• Diversion colitis, diverticular disease-
associated colitis, pouchitis
Histiocytic infiltrate• Infections
Atypical mycobacteriaFungal infectionsRhodococcus equiWhipple disease
• Xanthelasma• Storage disorders
Malakoplakia
• Abnormal phagocytic response to bacterial infections
• Immunodeficiency statesChronic diseases (SLE)Malignant neoplasms (colorectal cancer)
SummaryChronic colitis
• Crypt destructive (IBD-like)• Non-crypt destructive
Nonspecific ulcerCollagenous/lymphocytic colitisGranulomatousEosinophilic
Summary
Approach to diagnosis• Pattern
histological features• Etiologic diagnosis
clinical and endoscopic features
Are eosinophils increased??• Seasonal variation• Site variationsFavor pathologic states:• Eosinophilic cryptitis/crypt abscesses• Clusters in deeper mucosa/submucosa• Extracellular granules• Eosinophils predominate
Eosinophilic colitis
• PrimaryAllergic (Cow’s milk, soy protein) Idiopathic (eosinophilic gastroenteritis)
• Secondary
Eosinophilic colitis• Parasites• Iatrogenic
Drugs, radiation• Inflammatory bowel disease• Collagen vascular diseases
Rheumatoid arthritis, Churg-Strauss syndrome
• Tumor or tumor-like conditionsLeukemia/lymphoma Hypereosinophilic syndrome
Allergic colitis
• Infancy: most common cause of bloody diarrhea
• Peripheral eosinophilia often present• Eo >60/HPF has been suggested• Favorable outcome; can tolerate food by
1-3 years of age
Hypereosinophilic syndrome
• Eosinophilia (>1500/mm2) >6 months• No discernible cause• Organ system involvement
Heart, GI tract, lung
Prominent apoptosis“Apoptotic colopathy”
• Bowel preparation (oral sodium phosphate)
• Graft vs. host disease• Drugs• Nonspecific feature in inflammatory
colonic involvement by infections or other colitides
Focal active colitis
• Infections/self-limited colitis• Drugs, especially NSAIDs• Crohn disease• Effects of bowel preparation
Lymphoid folliclesFew cryptsNo chronic inflammation
Focal active colitis
• Adults5% have or develop Crohn disease
• Pediatric20% Crohn disease
Raise possibility only if clinically relevant
Chronic pouchitis
• Risk highest in first 2 years• Antibiotics, steroids• Severe refractory disease rare ~1%• Neoplastic changes rare
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