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 )

Definition:

“ Intestinal malabsorption of unknown etiology among residents or visitors to the tropics” Baker and Mathan

Tropical Sprue

Chronic malabsorption after infectious commonest in tropical regions Bacterial overgrowth with B-12 and Folate deficiencies - often responds to and vitamin supplements Biopsy findings are variable – Sprue-like changes with less intense damage than full blown celiac disease – Both and 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 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

-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, , 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 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 - 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 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 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

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 – 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