Infectious Lesions of the Lower GI Tract Joel K. Greenson, M.D. Department of Pathology University of Michigan Medical School Tropical Sprue (Post-Infective Tropical Malabsorption) Definition: “ Intestinal malabsorption of unknown etiology among residents or visitors to the tropics” Baker and Mathan Tropical Sprue Chronic malabsorption after infectious diarrhea commonest in tropical regions Bacterial overgrowth with B-12 and Folate deficiencies - often responds to antibiotics and vitamin supplements Biopsy findings are variable – Sprue-like changes with less intense damage than full blown celiac disease – Both Jejunum and Ileum involved Stasis Syndrome (Bacterial Overgrowth) Crohn’s Disease Diverticular Disease Scleroderma Pseudo-obstruction Post-Surgical – Blind loop or Pouch – Entero-enterostomy – Afferent loop – Fistulae - Adhesions/partial obstruction Bacterial Overgrowth Biopsy Findings Irregular Villi Surface cell damage Plasmacytosis Neutrophils Crypt Hyperplasia “Doesn’t fit” Whipple’ s Disease Described by George Whipple in 1907 as “intestinal lipodystrophy” – Whipple described rod shaped bacteria within lymphoid tissues and thought they might cause the disease Subsequently thought to be a lipid storage disorder until advent of EM in the early 1960’s Whipple’ s Disease Clinical Presentation: – Most patients are middle-aged white males – ? T cell defect, Associated with HLA-B27 – Present with diarrhea, malabsorption, weight loss and abdominal pain – Systemic and neurologic symptoms may overshadow GI complaints – May present with only CNS symptoms Whipple’ s Disease Histopathology Blunted and distorted villi – Contain macrophages, neutrophils, lipid droplets, and dilated lacteals Foamy macrophages fill the lamina propria – Granular PAS positive diastase resistant inclusions – May see PAS + rods in extracellular areas – AFB negative Whipple’s Disease Diagnostic Pitfalls False Positives: – Mycobacteria avium/intracellulare – Muciphages (rectal biopsy) – Lymph nodes (other PAS+ substances) False Negatives: – Sampling error – Submucosal form of disease – May have no histologic involvement but be PCR+ Muciphages PAS Alcian Blue ’ Whipple s Disease Diagnostic tests/Ancillary studies Small Bowel Biopsy – PAS stain – EM or Silver stain Blood Smear PCR – Tissue or blood Giardiasis Giardia lamblia - first protozoa discovered in the human intestine – Described by Leeuwenhoek in 1681 ( in his own stools) Most prevalent gut parasite in the U.S. (7.4%) May be endemic or epidemic – 23% of American travelers to Leningrad found to be infected over a 4 year period – Often spread by children via day care/school Giardiasis Epidemiology Fecal/oral spread - contaminated drinking water - intimate contact, “gay bowel disease” Children and patients with agammaglobulinemia, hypogammaglobulinemia, IgA deficiency, and/or achlorhydria are at increased risk Immunosupressed patients more likely to have chronic infection Giardiasis Clinical Symptoms: –Acute diarrhea with greasy foul smelling stools, no blood -Abdominal distention, bloating, pain, and flatulence -Weight loss and malabsorption Giardiasis Histopathology Trophozoites are identifiable on H&E stained sections - Ventral view: pear shaped body with 2 nuclei - Lateral view: Sickle shaped body - “Smudgy blue-grey blobs” that mimic extravesated mucus - Clumped together between villi or attached to epithelial surface, rare reports of invasion Giardiasis Histopathology Special stains may help bring out details of organism: trichrome, giemsa, PTAH or PAS Touch preps of biopsy may also help Inflammatory response is quite variable: – Some have normal biopsies, some have minor non-specific changes – Some get sprue-like changes, particularly hypogammaglobulinemic patients Where are the plasma cells? Giardiasis Biopsy techniques/ancillary studies Organisms are best found in distal duodenal or proximal jejunal biopsies Duodenal fluid aspirate or String test may have better yield Cysts may be identified in Stool exam (both cysts and trophs in stool if diarrhea is severe) Stool antigen test available Cryptosporidia C. parvum is the species – Organism lives within brush border – Common in animals, may be a zoonosis Healthy persons – ?Asymptomatic carrier state – Endemic and epidemic infections – Self-limited diarrheal illness Immunodeficient persons – Chronic diarrhea, malabsorption Cyclospora cayetanensis 1990s outbreak in US due to raspberries from Central America – foods contaminated by dirty water/poor sanitation Gastrointestinal symptoms – Diarrhea, nausea, vomiting, cramps Systemic manifestations – Fevers, chills, myalgias Immunocompetent or immunocompromised hosts Rx = Trimethoprim-sulfamethoxazole Isospora beli aka Cystoisospora Causes diarrhea which may be debilitating From contaminated drinking water Immunocompetent or immunocompromised hosts but most often seen in HIV Complex life cycle – bigger than cyclospora Rx = Trimethoprim-sulfamethoxazole but must stay on long term in HIV Cryptosporidia Isospora Cyclospora Microsporidia Enterocytozoon bieneusi 1985 - First described in a Hatian AIDS patient Causes profound watery diarrhea and a sclerosing cholangitis like illness (AIDS cholangiopathy) Most often found in small bowel, can be in biliary tree and colon Antimicrobial therapy not of much help – Albendazole inhibits spore formation but doesn’t kill the organism Acute Infectious-type Colitis Clinical Presentation Acute onset bloody diarrhea Similar symptoms are seen in acute onset UC Colon biopsies may be be required to distinguish between ASLC and new onset UC – provided the patient’s symptoms last long enough to get a referral to see a gastroenterologist Markers of Chronic Injury Forked or branched crypts Crypts shaped like animals, continents, or hebrew letters Paneth cells more distal than the right colon Basal plasma cells Acute Infectious-type Colitis Histopathology - Resolving ASLC Lamina propria may be hypercellular with increased lymphs, eos, polys, and a few plasma cells - Don’t be fooled into calling this chronic colitis! There may be an increase in intraepithelial lymphocytes such that the changes mimic lymphocytic colitis - Don’t be fooled, as the clinical history is not right for this! Acute Infectious-type Colitis Histopathology As ASLC resolves, there is mucus depletion with regenerative epithelial changes and a few residual foci of cryptitis or “focal active colitis” Clinical History 78 year-old man with past medical history of – COPD – type 2 diabetes mellitus – pulmonary hypertension – Degenerative joint disease – Chronic renal disease – GE reflux – Chronic anemia with eosinophilia, bone marrow showed eosinophilic hyperplasia in 2005 Clinical History Patient recently hospitalized for pneumonia and was treated with antibiotics and steroids Readmitted for shortness of breath Chest X-ray showed bilateral infiltrates Blood cultures + vancomycin-resistent enterococcus Patient developed abdominal pain and constipation CT scan showed diffuse thickening of right colon interpreted as “consistent with colitis” Clinical History Patient had colonoscopy which showed erythema and decreased vascular pattern Consistent with “mild non-specific colitis” Random biopsies were taken and submitted in one jar Chronic Colitis (so what’s the big deal?) Crypt distortion with increased chronic inflammation of the lamina propria and basal plasma cells in all biopsies – looks like typical Ulcerative Colitis Why are you wasting our time with this case? But wait there’s more! What’s this stuff? Giant cell and Eosinophils Histiocytes and Eosinophils Lots of Eosinophils StrongyloidesIt’s a Worm!!!!!! Stercoralis Strongyloidiasis Nematode endemic in tropics/sub tropics – Southeast Asia, Africa, South America, West Indies Also found in Southeastern US – Appalachia – Prevalence rate of 4% reported in Tennessee Complex life cycle that may replicate within human host and lead to chronic autoinfection – larvae penetrate skin when barefoot person steps in contaminated soil Strongyloides Colitis Review of 25 cases Qu et al, Human Pathology 2009 40(4):572-7. Strongyloidiasis may be right-sided, patchy and spare the rectum – pancolitis in 53% Eosinophilic microabscesses were seen in 30% Granulomas were seen in 44% Few crypt abscesses but frequent ulcers 52% initially misdiagnosed, 38.5% were called UC Fatality rate of 39% (may be as high as 90%) Strongyloides Clinical Up to 30% of infected patients are asymptomatic Most immunosuppressed patients have symptoms – Abdominal pain, diarrhea, nausea &vomiting/obstruction, pruritus ani – Dry cough, dyspnea, wheezing, hemoptysis Acute syndrome of cutaneous, pulmonary and GI symptoms may occur Peripheral blood eosinophilia Strongyloidiasis Stool testing is not very sensitive (must repeat mutliple times). – May need >7 samples to get to 90% sensitivity Duodenal fluid aspirate is most sensitive way to make a diagnosis (biopsy may be just as good?) There is an Elisa serologic test available as well Treatment is effective (if started in time) – Albendazole, thiabendazole and or ivermectin .