Infections of the GI tract. K. Geboes, KULeuven, Dept of Pathology 2009

Transcription

1 Infections of the GI tract K. Geboes, KULeuven, Dept of Pathology 2009

2 Content Introduction Methods Viral infections Fungi Protozoa Bacteria Non specific Specific Helminths

3 Infections and GI tract Functional lesions Secretion (diarrhea cholera) Disturbed motility (acute and chronic diarrhea) Malabsorption - Itis & Mucosal defects Erosion; ulcer; polyposis (Schistosoma..) Transmural lesions Abscess; cysts; granulomas Ischemia Ischemic type of disease Vascular thromboses (aspergillus) Vasculitis! (CMV) Cancer Bacteria Hp and Cancer and Lymphoma of the stomach Campylobacter jejuni and lymphoma of the small intestine (alpha chain disease) Helminths Schistosoma and colorectal cancer Virus EBV and cancer Herpes

4 Infections and GI tract Healthy individuals Bacterial Viral Other Travellers / Migrants Classical tropical Extraordinary Impaired Host response - Opportunistic infections Fungi Virus Bacteria Protozoa underlying malignancy, diabetes, alcoholism immunosuppressive or steroid therapy transplants broad spectrum antibiotics irradiation, HIV, hypoacidity of stomach, interference with peristalsis (strictures; bacterial overgrowth )

5 Microscopy Tissue analysis and Infections and GI tract - Methods Morphology Routine histology/cytology Special stains Identification of pathogen Identification of specific lesions (granulomas ) Immunohistochemistry/ In situ hybridization/fish Transmission electron microscopy Culture based Molecular techniques 16s ribosomal nucleic acid PCR Laser microdissection and PCR

6 Tissue analysis and Infections of GI tract Methods Mucosal biopsies > adherent organisms; invasive organisms Patchy lesions Diffuse involvement Surgical specimens > intraluminal organism; intramural organisms Smear cytology : adherent organisms

7 Tissue analysis and Infections of GI tract Methods Identification of specific lesions cells Whartin-Finkeldey cells > measles Identification of microörganisms Giardia Amoebae CMV Lesions suggestive of infection Specific lesions (granulomas) > TBC, Yersinia, Other Generally suggestive of infectious (entero-)colitis Unspecific lesions Oedema Ischemic type of lesions

8 Specific lesions cells Appendicitis and measles Whartin Finkeldey cells Cytology Giardia Lamblia

9 Yersinia enterocolitica

10 16S rdna gene Present in all bacteria Only in bacteria Conserved and variable regions Sequence determination may assist in identification of bacteria PCR TGGE, DGGE / cloning & sequencing / FISH

11 Microdissection Crohn s disease, myenteric plexus 3 controls (1 IL, 2 COL): Bacillaceae in 1 COL sample (close to an adenocarcinoma) 4 CD patients (IL): Streptococcaceae in 1 pt 3/4 pts Legionellaceae in the myenteric plexus of a diseased ileal segment (all 3 carried a CD risk variant of the CARD15 BEFORE gene) merits further investigation!

12 Virus

13 Viral Infections Herpes Location Oesophagus Most common visceral site Reactivation of latent virus in ganglion cells Healthy individuals Immunosuppressed (more common) Stomach Rare Terminally ill patients / bone marrow transplant Rectum - anus In AIDS > (pseudo)tumors hypertrophic verrucous lesion (Dis Col Rect 2005) Sexually transmitted disease Combination with other infections : Candida / HIV Microscopy Routine H&E : Infected epithelial cells with typical inclusions (Cowdry A); multinucleated giant cells Immunohistochemistry

14 Location Viral Infections Cytomegalovirus Oesophagus Opportunistic Stomach Neonates Healthy adults (occasionally) Opportunistic (HIV : 13%; transplants ; 50%) Small Intestine Opportunistic Colon Primary infection : controversial role Opportunistic (transplants ) Ulcerative colitis

15 1st description, 1961 (Powell e.a. Am J Med, 30; ) relationship : undetermined innocent bystander superinfection initiation of disease (primary disease) UC & CMV

16 UC & CMV Reactivation of infection might exacerbate colitis

17 IBD and CMV Prevalence 4.6% (UC) Kaufman e.a. Dis colon Rectum 1999, 42: % in acute severe colitis Kandiel & Lashner Am J Gastroenterol 2006, 101: /19 (36%) pts with refractory IBD (5 = UC) Cottone e.a. Am J Gastroenterol 2001, 96: % in steroid refractory UC 45 cases reported in English literature ( ) Nishimoto e.a. Gastrointest End 2001, 53, 816

18 UC & CMV UC & CMV colitis : 33-44% mortality (Berk e.a. Am J Gastroenterol 1985, 80, ) Therefore : proper diagnosis & treatment Histology (gold standard, Lortholy e.a. Eur J Clin Microbiol Infect Dis 1993, 12, 570-2) Serology: complement fixation antibody (IgM) CMV antigen detection : CMV antibody testing (IgG-, IgM- ) with Elisa (Enzyme-linked immunosorbent assay); MEIA (Microparticle enzyme immuno assay) PCR pp-65 antigen PCR Culture (blood, urine, tissue...)

19 CMV Immunohistochemistry

20 Other viruses HIV (not detectable by morphology) Small intestine Viral gastroenteritis mainly in children (outbreaks) Norwalk agent : supranuclear vacuolization of enterocytes (not typical) Rotavirus : TEM Adenovirus : Immunohistochemistry Picorna virus

21 HIV & Crohn Remission of Crohn s disease after human immunodeficiency virus infection. James SP Gastroenterology 1988; 95: 1667 Remission associated with progressive immunodeficiency role of CD4 Crohn s ileitis in a patient with longstanding HIV infection. Bernstein e.a. Am J Gastroenterol 1994; 89: 937 Development of Crohn, no prior history

22 Fungi

23 Fungal infections Colonization of ulcers (candida) Others > immunodeficiencies Histoplasmosis Mucormycosis Aspergillosis > small intestine (blood vessels)

24 Primary immunodeficiencies? B Male pt 17yrs old Mononucleosis; appendicitis with perforation and peritonitis Subsequently : septicemia (gram+ cocci) Invasive aspergillosis with cutaneous lesions and massive ischemic necrosis of small bowel Herpes infection Multiple organ failure X-linked primary immuno deficiency (Fatal hemophagocytic lymphohistiocytosis associated with Epstein- Barr virus infection in a patient with a novel mutation in the signaling lymphocytic activation molecule-associated protein) Halasa et al Clinical Infectious Diseases 2003)

25 Protozoa

26 Coccidiosis (obligate intracellular parasites) Cryptosporidiosis Cryptosporidium parvum infects humans Associated with HIV AIDs Traveller s diarrhea (self limiting disease) Outbreaks of diarrhea in immunocompetent patients (water supplies) Location Stomach Antrum more common than corpus - patchy Organisms on luminal border of epithelial cells of gastic pits non specific chronic inflammation Small intestine Mucosa normal in immunocompetent Villous atrophy in HIV pts (in pts with severe disease) Colon

27 Cryptosporidia

28 Amoebiasis Entamoeba histolytica Worldwide distribution (more common in tropics) Location Small intestine Colon Macroscopy Ulcers flask shaped (caecum, ascendens, rectum) Diffuse colitis Inflammatory polyposis

29 Microscopy Amoebiasis Entamoeba histolytica Inflammation : around ulcers, tissue damage Cysts or active forms usually in a pool of mucus at the edge of the ulcer

30 Ulcerative colitis & Amoebiasis Differential diagnosis with UC but primary target of amoebiasis = right colon (Brandt e.a. Hum Pathol, 1970) acute colitis fulminant colitis Combination of UC and amoebiasis traveller s disease IBD pts can be carriers (cave steroids Inappropriate treatment with corticosteroids complications (liver abscess; toxic megacolon)

31 Bacteria Identification Specific lesions Special stains (gram, Whartin-Starry.) Immunohistochemistry Infectious colitis due to histologically nonidentifiable agents

32 Acute diarrhoea etiology Watery diarrhoea TOXINS Mushroom - seafood PHARMACOLOGICAL AGENTS misoprostol - laxatives INFECTIONS preformed bacterial toxins viruses bacteria : Vibrio cholerae; Salmonella... others : Giardia

33 Acute diarrhoea etiology Acute bloody diarrhoea Invasive pathogens Shigella Campylobacter jejuni, coli Salmonella Yersinia... Cytotoxin producing pathogens C. difficile Vibrio parahaemolyticus

34 Chronic diarrhoea definition, etiology Three or more loose stools for more than 30 days (adults) ; 14 days (children) Infectious causes viruses rota, CMV, adeno bacteria Aeromonas hydrophilia Campylobacter jejuni Enteropathogenic E. coli Yersinia Plesiomonas Mycobacteria & atypical mycobacteria Protozoa Helminths

35 Campylobacter coli

36 Infective-type colitis General morphological features Variability in time (natural course of disease) due to virulence differences toxins toxins and invasion host reaction Spectrum of microscopic features normal biopsy toxins Vibrio ch, Klebsiella oedema active inflammation invasion Yersinia, Campylo fulminant lesions (extensive necrosis) residual lesions

37 Infective-type colitis General morphological features Architecture NORMAL (except...) Inflammation NEUTROPHILS (active acute) early (day 1-7) superficial upper part of lamina propria upper part of crypts MONONUCLEAR CELLS late (day 9,10) superficial (except...) DISTRIBUTION focal - patchy

38 IBD and superinfection at relapse Species CD UC C. difficile 4 1 Salmonella typhimurium 0 1 Campylobacter jejuni 1 0 Enteropathogenic E. coli 3 0 Initial nr of patients Total nr positive 9(18%) 2(13%) Weber e.a. J Clin Gastroenterol 1992, 14, 302-8

39 Specific bacterial infections

40 Human Intestinal Spirochetosis > Less common in children? Usually asymptomatic Pathogen/commensal? incidence in homosexual men and immunocompromised (AIDS) pts

41 Intestinal Tuberculosis

42 Intestinal Tuberculosis Rare in Western world Usually secondary Location : usually terminal ileum, caecum and appendix Colon and rectum (less common) Anorectum : fistula Macroscopy Transverse ulcers (Crohn = longitudinal) Microscopy Granulomatous inflammation (with necrosis) Confluent small granulomas

43 IBD & Tuberculosis Differential diagnosis Complication

44 IBD & Tuberculosis Infliximab : Postmarketing experience Tuberculosis :0.04% (55 cases) 31% disseminated 13% Deaths Onset of tuberculosis : risk = early; after 1 or 2 infusions

45 Helminths

46 Schistosomiasis / Bilharziasis Schistosoma mansoni (Africa, the Caribbean, Middle East, Sout America) Penetration of human skin migration to liver relocation to mesenteric veins Production of eggs Migration into intestinal wall Chronic disease Diarrhea bloody Colonic polyposis Portal hypertension Pathology Inflammatory reaction to eggs Portal colopathy

47 Schistosomiasis / Bilharziasis Pathology Early stage : acute proctitis colitis Chronic infection Localized or diffuse ulceration Strictures Pericolic mass Polyposis Microscopy Biopsy diagnosis + in up to 80% of cases (in endemic areas) Eggs with infl reaction Granulomas Lymphocytes/eosino s

48 Schistosomiasis

49 Widely spread Affects mainly small intestine (& stomach) Can remain dormant for a long period Rare in colon Immunocompromised hosts Pts with active ulcerative colitis (4%) in tropical countries (Banerjee e.a. Scand J Gastroenterol 2008, Strongyloidiasis

50 Conclusions Inflammatory disorders of the large bowel are common (sometimes in association with small bowel) Infections are more usually diagnosed by microbiological methods and often do not require histology The histology of bacterial infections is variable and not specific Viral infection of the colon is not so common Pathogens can be detected by specific lesions, or by identification of the pathogen Inflammation is usually widespread : for a precise diagnosis multiple biopsies are superior.