Diarrhea Part II: The Immunosuppressed Patient

1. Diarrhea Part II:The Immunosuppressed Patient Jonathon Sullivan MD, PhD Dept of Emergency Medicine Wayne State University

2. FOR SOME WEIRD REASON… • Ayesha thinks I know more about this than you do. • Disclaimer follows.

4. Agenda • Review • The Bug Parade • Usual pathogens • Opportunistic pathogens • Weird pathogens • Organ Transplants • Bottom line: call attending and/or admit. • HIV Diarrhea • Infectious • Drug-Related • Secondary • Approach to HIV+Acute Diarrhea

5. REVIEW OF BASIC SQUIRTOLOGY • A quick reprise of some of the high (and low) points of Diarrhea Part I. r‘mber Me?

6. Causes of Morbidity and Mortality • Dehydration, Dehydration, Dehydration • Electrolyte depletion and malnutrition • Bacteremia/Sepsis • Perforation, megacolon • Underlying condition

7. The Runs Come in 4 Flavors • Secretory • Cholera, viral gastroenteritis • Inflammatory • Dysentery (eg, She-Gella, Amy the Ameba) • Chemo • IBD • Radiation poisoning • Osmotic • Congenital • Drugs • Lactose intolerance and other dietary causes • Motility

8. Inflammatory Diarrhea • Results from damage to intestinal mucosa. • Unable to resorb water, electrolytes, proteins. • Loss of fluid, lytes and blood. • Includes the dysenteries, in which the organism adheres to lining. Blood and white cells in stool.

9. Secretory Diarrhea • Active secretion of water and electrolytes (primarily chloride) into the gut lumen. • Results from increased cellular permeability. • Toxins • Viral damage • Minimal if any blood, no leukocytes • May nevertheless be severe.

10. Osmotic Diarrhea • Water and electrolytes are pulled into the lumen due to a high osmotic load. • This osmotic load can be due to: • Certain laxatives: Glycerin suppositories, Sorbitol, Lactulose, and Polyethylene glycol (PEG). • Malabsorption: pancreatic disease, celiac disease, etc. Leaves nutrients (osm load) in the lumen.

11. Hypermotility • Not enough time for nutrients to be absorbed before they shoot out. • Vagotomy • Diabetic neuropathy • Menstruation • Prokinetic drugs • Idiopathic • Diagnosis of exlusion.

12. Or, If You Prefer, These 4 Flavors *lumps together invasive, inflammatory, non-amebic dysenteries, etc.

13. Invasive vs. Noninvase

14. Approach to the Runny Patient • ABCs, resuscitation if necessary. • Fluids, electrolytes, EKG, accucheck, temp control • History: • Diet: uncooked meat, fish, unpasteurized dairy, sick contacts, last meal, etc. • Stool frequency, consistency, odor, blood, mucus, etc. • AP, bloating, N/V, F/C, urinary frequency, etc. • MEDICATIONS, especially HAART and recent antibiotic use. • History of opportunistic infections • Travel

15. Approach to the Runny Patient • Physical Exam: • VS: tachycardia, hypotnesion, fever • Volume status: turgor, sunken eyes, mucus membranes, cap refill • Abdominal exam • Rectal (yes, everybody): blood, pus, associated rectal and perirectal lesions • Contraindications: • neutropenia • No consent • No rectum • No finger

16. OUR CAST OF CHARACTERSaka The Bug Parade • Three Categories: • The Usual Suspects • Crass Opportunists • Pathogens From Another Galaxy

17. Usual Pathogens • Our Old Friends: • She-Gella • Sal Monella • Campy Lo-Backed Her • Be Cereus! • Gee, Our Diarrhea (Lambia) • Amy the Ameba • Your Sin, Yee-Ha! • Si Difficile

18. Opportunistic Pathogens • Cyto Megaton Virus • Adenovirus • HSV • MAC • Tales from the Cryptosporidium • Isospora and Cyclospora

19. Pathogens from Another Galaxy • Balantidium coli • Blastocystis hominis • Encephalitozoon intestinalis

20. Most Common Infectious Causes of Diarrhea in Immunocompromised • HIV: • Shigella • Salmonella • Campylobacter • Acute Post-Transplant (w/in 6 mos) • CMV, CMV, CMV • Giardia • Cryptosporidium

21. Shigella! Shi sure is.

22. Invasive and Inflammatory Diarrhea • Shigella • Highly communicable • Toxic patient with high fever, very loose, bloody, watery stools, +/- pus • febrile seizures. • Straining at stool • Reactive arthritis • Incubation from 2-7 days. • Cipro, TMP/SMX • Some association with HUS (Shigatoxin)

23. Don’t Confuse Them: Salmonella Sal Mineo Treatment Required No Treatment

24. Invasive and Inflammatory Diarrhea • Salmonella • Eggs, reptiles and amphibians, chickens, improperly treated foods, Pizza Papalis in Mod 5, esp w. reptile toppings. • Typhoid (meaning “typhus-like”) fever: • Relative bradycardia • Abdominal pain, borborygmi • Leukopenia with eosinophilia • Rash • Hepatosplenomegaly • +/- diarrhea • Vaccine • Trivia points: what causes typhus?

25. Campylobacter!

26. Invasive and Inflammatory Diarrhea • Campylobacter • Most common bacterial squirtosis • Most common route: fecal-oral • In a perfect world, these two words would never go together. • Improper food preparation • Beef, pork etc. But mostly it tastes…just like chicken. • Associated with HUS, TTP, and Guillan-Barre (!)

27. Warp Drive Engines Cargo Hold Diarrhea Ray Cockpit Backpackers Beware!

28. Giardia Lambia • Most common intestinal parasite in N. America • Rivers, streams, ponds, pools, daycare • Fecal-oral, anal receptive intercourse. • Long incubation: up to two weeks. • Nonbloody, noninflammatory diarrhea • Target the warp drive nacelles: Flagyl.

29. Tales from the Cryptosporidium! Cthulhu Lives!

30. Cryptosporidium • Crytposporidium sux. • Multiple species. • Contaminated water, travelers. • Spores are highly resistant to chlorination and some disinfectants. • Young children and immunocompromised are at high risk. • Dx: serology, acid-fast staining of stool oocytes, intestinal biopsy. • No proven therapy. Paromomycin may help. May require reduction of immunosuppression.

31. Amy!

32. Amy the Ameba is Not Your Friend • Kills 70,000/yr worldwide. • Amebiasis may be asymptomatic, or present with mild diarrhea or full-blown dysentery with blood and mucus • Liver and CNS abscesses, pericarditis(!). • Fecal-oral, anal receptive, water contamination. Reason # 527 to wash your hands. • Pt may be colonized and asx until Amy penetrates mucus and enzymes damage gut wall. • Dx: Serology, assay kits, microscopy. • Metronidazole, paromycin (16S rRNA binder), iodoquinol.

33. Si, Difficile!

34. Pseudomembranous Enterocolitis • Overgrowth of toxin-producing C. Difficile • 7-10 days after antibiotics • Patients often look toxic, febrile • ELISA • Stop antibiotics • Flagyl or vanc, hydration, etc. • Let ‘em squirt. DO NOT poison these patients with antimotility drugs • Because you’ll kill them.

35. C. Difficile Be Difficile • Half of transplant patients who get Abx will develop C. Diff enterocolitis. • Full clinical spectrum: • Uncomplicated diarrhea • Enterocolitis • Toxic Megacolon • Transplant + Diarrhea + Abdominal Pain = Xrays

36. Cyto Megatron Virus! I DON’T FEEL SO GOOD. Megatron’s diarrhea comes out here.

37. CMV • AKA Human Herpesvirus 5 or HCMV • 50-80% of the population has α-CMV Ig, indicating latent infection. • Immunocompromised: acute infection vs. reactivation of latent virus. • Most common infection causing symptoms after transplant (esp intestinal transplants). • Tx: • ganciclovir, valganciclovir, foscarnet, cidofovir • BTW: These all causediarrhea. Good luck, doctor. • supportive care.

38. Isospora!

39. Isospora Belli • Protist of the coccidia subclass. • Closely related to Toxoplasma gondii and cryptosporidium. • Dogs are an important reservoir. • Fecal-oral transmission. • Diarrhea, bloating, misery. • TMP-SMX. Response varies.

40. Cyclospora!

41. Cyclospora cayetanensis • Related to Isospora spp. • Frequent cause of traveller’s diarrhea or “yuppie diarrhea” (organic raspberries from the co-op, anyone?) • Dx: good luck. Try PCR, serial stool samples, phase-contrast microscopy. • TMP-SMX.

42. Pathogens from Another Galaxy! Balantidium Blastocystosis GREETINGS, EARTHLING. YOUR BOWEL HABITS, AS YOU HAVE KNOWN THEM, ARE NOW OVER. Encephalitozoon

43. Intergalactic Squirtosis • Balantidium coli. Ciliated protozoan. • Fecal-oral route. • Tetracycline or diiodohydroxyquin. • Blastocystis hominis. Single-celled parasite (order Blastocystida) • Implicated in IBS (aka Mountain Girl syndrome) • Multiple animal reservoirs. • TMP-SMX? • Encephalitozoon intestinalis.A very primitive fungus among us (order Microsporidia). • Forms a multinucleate plasmodium in the host cell. • You don’t have to know exactly what this means to know you don’t like it. • Just weird. Don’t even have mitochondria. • Dx: Good luck. Special PCR techniques. • Tx: Good luck. Try antifungals, fluoroquinolones. Your sophisticated drugs are no match for our primitive biology!

44. Organ Transplants • 30,000 per year • Diarrhea is a common complication • Can result in badness. • Differential: • Infection • GVH (BMT) • Std vs. Opportunistic spp. • Antibiotic effect • Immunosuppressant effect

45. Organ Transplants • Up to 6 months after transplant, or during rejection or increased immunosuppression: • Opportunistic and viral infections • Giardia • Cryptosporidium • CMV • Isospora • Cyclospora • Microsporidium • Strongyloides

46. Organ Transplants • After 6 months, if graft takes well: • More typical, comm-acquired etiologies: • C. Difficile • Yersinia • Salmonella • Campy-Low-Backed-Her • Listeria

47. Approach to the Post-Transplant Patient with Acute Diarrhea • ABCs, supportive care (fluids, fluids, fluids) • Consider isolation protocol • Strongly consider C. Difficile (esp if recent abx) and CMV. • Stool for Cx, O&P • Call Transplant Surgeon and PMD! • Most cases require admission

48. ACUTE DIARRHEA IN HIV DISEASE • 50-90% of all AIDS patients. • Multiple etiologies: • Infectious • Drug-related • HIV enteropathy • lymphoma, GI Kaposi’s • Hydration, sample collection, strongly consider admission, consult with ID.

49. ACUTE DIARRHEA IN HIV DISEASE • Infectious: • Most common: Shigella, salmonella, campylobacter, cryptosporidium, Isospora, CMV, MAC, and C.Difficile. • Bacterial: more fulminant • Viral and parasitic: more indolent • Unlike “normal” patients, patients with HIV + diarrhea usually require testing aimed at isolating the pathogen (or lack thereof).

50. ACUTE DIARRHEA IN HIV DISEASE • Drug-related • Anti-retroviral therapy (all except Indinavir), especially HAART (mitochondrial suppression with adenosine-based ARVs--check lactate) • Antibiotic therapy • Atovaquon • Macrolides • Ganciclovir, Foscarnet • Antifungalls • Post-antibiotic therapy • C. Difficile • Analgesics • NSAIDS • Narcotics (!)