1. Gastrointestinal Pathology Evening Specialty Conference March 17, 2016
Laura W. Lamps, MD
Professor and Vice Chair of Academic Affairs
University of Arkansas for Medical Sciences
Little Rock, AR

2. Clinical Summary 40 year old woman with HIV
Undetectable viral loads for more than 15 years
15 month history of episodic nausea, vomiting, diarrhea
Some episodes resolved spontaneously
Others severe, requiring hospitalization for dehydration

3. Clinical Summary
Patient originally from Ethiopia, occasionally traveled there
Lived in Western US for many years
Symptoms do not correlate with travel
Previous EGD/colonoscopy normal x2; normal capsule endoscopy

4. Clinical Summary Laboratory Data
Peripheral eosinophilia
Stool O&P repeatedly negative
Positive Strongyloides antibody; all other infectious disease serologies negative

12. Diagnosis:
Cystoisosporiasis

13. Cystoisosporiasis Cystoisospora belli (formerly Isospora belli)
Obligate intracellular coccidian parasite with worldwide distribution
Especially common in tropical/subtropical climates
Ubiquitous in animal kingdom
Transmission through food, water

14. Cystoisosporiasis Originally described in soldiers during WWI and WWII
Rare in USA prior to AIDS epidemic
Prevalence in Western countries ~ 5%
Prevalence in developing countries ~10-15%

15. Cystoisosporiasis Life cycle
Complex to say the least
Ingestion, followed by excystation and invasion
Asexual division produces more organisms that infect more cells
Some enter the sexual phase, develop male and female gametes, fertilization occurs, oocysts released into the lumen
Sexual forms can autoinfect or pass in the stool to continue the cycle

16. Cystoisospora
Life Cycle

17. Cystoisosporiasis Clinical
Immunocompetent patients
Typically asymptomatic diarrheal infections
Immune compromised patients
Watery nonbloody diarrhea, dehydration
Abdominal pain
Nausea, vomiting
Fever, malaise

18. Cystoisosporiasis Clinical
Infection more severe in immunocompromised patients
Severe malabsorption, dehydration, cachexia, dissemination
Many cases respond to antiobiotics (Bactrim), so important to recognize infection

19. Cystoisosporiasis Clinical
Peripheral eosinophilia common
Charcot-Leyden crystals may be seen in stool
EGD/colonoscopy usually normal
Occasionally mild erythema
Stool studies
Usually not helpful unless special stains requested

20. Variably present villous blunting, surface disarray, increased IELs
Eosinophils usually prominent in GI specimens but not biliary

21. Parasitophorous vacuole
is characteristic

22. PAS

23. Giemsa

24. Cystoisospora Biliary infection
Symptomatic cholangitis, typically in AIDS patients
Reported in gallbladders from liver donors, cholecystectomy for biliary dyskinesia in otherwise healthy patients
Often minimal tissue reaction

25. Courtesy Dr. Keith Lai

26. Diagnosis Light microscopy Stool O&P PCR from stool
Sensitivity/specificity variable depending on technique (40-100%; %)
Acid fast stains, antigen detection techniques
PCR from stool
87-100% sensitivity; % specificity

27. Differential Diagnosis
Other things that cause villous blunting +/- eosinophils
Celiac disease
Idiopathic eosinophilic enteritis
Adverse drug effect
Food allergy

28. Idiopathic eosinophilic enteritis

29. Olmesartan toxicity

30. Differential Diagnosis
Other coccidians
Other intracellular organisms
Will almost always be within macrophages, and not at the luminal surface of the epithelium
Leishmania
Toxoplasmosis
Fungi (Histoplasmosis, P. marneffei)

31. Comparison of Enteric “Coccidians*”
Feature
Microsporidia
Cryptosporidia
Cyclospora
Cystoisospora
Size
2-3µ (smallest)
2-5 µ
2-3µ schizonts
5-6µ merozoites
15-20µ (largest)
Location
Epithelial cells
Apical surface
Upper epithelium
Epithelium
Macrophages
Staining
Mod trichrome
Giemsa
Gram
W-S
PAS
Acid fast
Auramine
GMS
Other
Birefringent under polarized light
Bulges out of luminal apex of enterocyte
Parasitophorous vacuole
Eosinophils
*Microsporidia are now classified as fungi
*Cryptosporidia are still parasites, but Gregorines, not coccidia

32. Cryptosporidium

33. Microsporidia

34. Modified trichrome stain highlights organisms

35. Cyclospora: surface epithelial cell disarray
Case and pictures courtesy of Dr. Rhonda Yantiss

36. Round schizonts and banana shaped merozoites in parasitophorous vacuoles

37. Differential Diagnosis
Other coccidians
Other intracellular organisms
Will almost always be within macrophages, and not at the luminal surface of the epithelium
Leishmania
Toxoplasmosis
Fungi (Histoplasmosis, P. marneffei)

38. P. marneffei

39. Histoplasmosis

40. Summary/Take Home
Cystoisospora is the largest coccidian, but easily missed
Associated histologic findings may be subtle, so remember to look for them
They are treatable with antibiotics
Not limited to immunocompromised patients
Stool studies can be helpful