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Diarrhea Part II: The Immunosuppressed Patient Jonathon Sullivan MD, PhD Dept of Emergency Medicine Wayne State University FOR SOME WEIRD REASON… Ayesha thinks I know more about this than you do. Disclaimer follows. Agenda Review The Bug Parade Organ Transplants Usual pathogens Opportunistic pathogens Weird pathogens Bottom line: call attending and/or admit. HIV Diarrhea Infectious Drug-Related Secondary Approach to HIV+Acute Diarrhea REVIEW OF BASIC SQUIRTOLOGY A quick reprise of some of the high (and low) points of Diarrhea Part I. r‘mber Me? Causes of Morbidity and Mortality Dehydration, Dehydration, Dehydration Electrolyte depletion and malnutrition Bacteremia/Sepsis Perforation, megacolon Underlying condition The Runs Come in 4 Flavors Secretory Inflammatory Dysentery (eg, She-Gella, Amy the Ameba) Chemo IBD Radiation poisoning Osmotic Cholera, viral gastroenteritis Congenital Drugs Lactose intolerance and other dietary causes Motility 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. 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. 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. Hypermotility Not enough time for nutrients to be absorbed before they shoot out. Vagotomy Diabetic neuropathy Menstruation Prokinetic drugs Idiopathic Diagnosis of exlusion. Or, If You Prefer, These 4 Flavors Viral Protozoan CMV, Rota, adeno, enterovirus, Norwalk Giardia, Amy the Ameba, Cryptosporidium “Invasive” Toxicogenic/Secretory E. Coli 0157:H7, Shigella Salmonella, Vibrios, Campy Low-Backed Her, Your Sin Yee-Hah Staph, noninvasive E. Coli, Be Serious, C. Difficile, Cholera *lumps together invasive, inflammatory, non-amebic dysenteries, etc. Invasive vs. Noninvase “INVASIVE” “NONINVASIVE” Heme Positive Heme Negative Shigella and Salmonella ETEC, EPEC Campylobacter Cholera (V. cholerae) Entameba histolytica Other Vibrios Yersinia enterocolitica Clostridium perfringens EHEC Be Serious! Norwalk Giardia Cryptosporidia Rota, parvovirus, weird protists 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 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 OUR CAST OF CHARACTERS aka The Bug Parade Three Categories: The Usual Suspects Crass Opportunists Pathogens From Another Galaxy 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 Opportunistic Pathogens Cyto Megaton Virus Adenovirus HSV MAC Tales from the Cryptosporidium Isospora and Cyclospora Pathogens from Another Galaxy Balantidium coli Blastocystis hominis Encephalitozoon intestinalis Most Common Infectious Causes of Diarrhea in Immunocompromised HIV: Shigella Salmonella Campylobacter Acute Post-Transplant (w/in 6 mos) CMV, CMV, CMV Giardia Cryptosporidium Shigella! Shi sure is. 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) Don’t Confuse Them: Sal Mineo Salmonella No Treatment Treatment Required 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? Campylobacter! 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 (!) Backpackers Beware! Warp Drive Engines Cargo Hold Diarrhea Ray Cockpit 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. Tales from the Cryptosporidium! Cthulhu Lives! 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. Amy! 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. Si, Difficile! 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. 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 Cyto Megatron Virus! I DON’T FEEL SO GOOD. Megatron’s diarrhea comes out here. 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 cause diarrhea. Good luck, doctor. supportive care. Isospora! 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. Cyclospora! 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. Pathogens from Another Galaxy! Balantidium Blastocystosis GREETINGS, EARTHLING. YOUR BOWEL HABITS, AS YOU HAVE KNOWN THEM, ARE NOW OVER. Encephalitozoon Intergalactic Squirtosis Balantidium coli. Ciliated protozoan. Blastocystis hominis. Single-celled parasite (order Blastocystida) Fecal-oral route. Tetracycline or diiodohydroxyquin. 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! 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 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 Organ Transplants After 6 months, if graft takes well: More typical, comm-acquired etiologies: C. Difficile Yersinia Salmonella Campy-Low-Backed-Her Listeria 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 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. 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). ACUTE DIARRHEA IN HIV DISEASE Drug-related Anti-retroviral therapy (all except Indinavir), especially HAART (mitochondrial suppression with adenosinebased ARVs--check lactate) Antibiotic therapy Atovaquon Macrolides Ganciclovir, Foscarnet Antifungalls Post-antibiotic therapy C. Difficile Analgesics NSAIDS Narcotics (!) ACUTE DIARRHEA IN HIV DISEASE HIV/AIDS enteropathy Severe, high-volume, watery diarrhea. Typically end-stage patients. No pathogen identified. Admission almost always required. Octreotide may help. Management ABCs! A: Avoid introducing diarrhea into the airway. B: Avoid breathing in the diarrhea. C = replace that volume loss! Oral vs. IV IV NS vs. Juice vs. Soup n’ crackers. Sucrose? Worse or better? Replace electrolytes Endpoints: improve in clinical hydration status, improve symptoms, make pee-pee. ACUTE DIARRHEA ASSESS FOR PERF (THINK S. TYPHII) LAB: CBC, LYTES, CD4, O&P, Cx, FECAL LEUKOCYTES. CONSIDER SMEAR FOR MALARIA. CONSIDER WIDAL TEST OR TYPHIDOT. ABDOMINAL PAIN? FEVER? FLUIDS, OBSERVE 24-72 hr. CIPRO; BACTRIM + FLAGYL FURROW BROW; GO TO NEXT SLIDE ACUTE DIARRHEA + HIV + ABD PAIN AND/OR FEVER = ADMIT HYPOTENSION ACUTE ABD NO PO’S? Y 1. 2. 3. 4. FREAK OUT CALL SURG IVFs ARE GOOD. THINK SAL, SHIG AND S. TYPHII 5. CEFTRIAX + FLAGYL OR CIPRO 6. XRAYS 7. EGDT IF NEC O&P POSITIVE? N Y N TENESMUS OR BLOODY STOOL? BLOATING OR FLATULANCE? Y Y TREAT FOR AMY THE AMEBA: FLAGYL N TX FOR COCCIDIA, etc. BACTRIM 14d TREAT FOR GIARDIA: FLAGYL N Tx FOR SAL, SHIG, CAMPY, YERS. BACTRIM or CIPRO 14d DISPOSITION DISCHARGE CRITERIA: Nontoxic. No abdominal pain upon presentation or subsequently. No fever. Euvolemic. Normal vital signs. Able to tolerate liquids and take medications. Able to GET medications. CLOSE FOLLOWUP ARRANGED. ADMISSION CRITERIA: Opposite of the discharge criteria. Duh. ALWAYS discuss patient with primary if available; arrange CLOSE follow up for discharged patients. No primary? STRONGLY consider admission ? Gimme. No good data. Sullydog approves, provided you dilute to 1/3 with water.