Transcript Diarrhea Part II: The Immunosuppressed Patient

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.
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Agenda
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Review
The Bug Parade
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Organ Transplants
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Usual pathogens
Opportunistic pathogens
Weird pathogens
Bottom line: call attending and/or admit.
HIV Diarrhea
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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
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Perforation, megacolon
Underlying condition
The Runs Come in 4 Flavors
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Secretory
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Inflammatory
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Dysentery (eg, She-Gella, Amy the Ameba)
Chemo
IBD
Radiation poisoning
Osmotic
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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.
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Secretory Diarrhea
Active secretion of water and electrolytes
(primarily chloride) into the gut lumen.
 Results from increased cellular
permeability.
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Toxins
 Viral damage
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Minimal if any blood, no leukocytes
 May nevertheless be severe.
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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.
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Hypermotility
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Not enough time for nutrients to be
absorbed before they shoot out.
Vagotomy
 Diabetic neuropathy
 Menstruation
 Prokinetic drugs
 Idiopathic
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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
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ABCs, resuscitation if necessary.
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Fluids, electrolytes, EKG, accucheck, temp control
History:
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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
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Physical Exam:
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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
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Contraindications:
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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
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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
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Cyto Megaton Virus
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Adenovirus
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HSV
MAC
Tales from the Cryptosporidium
Isospora and Cyclospora
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Pathogens from Another Galaxy
Balantidium coli
 Blastocystis hominis
 Encephalitozoon intestinalis
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Most Common Infectious Causes of
Diarrhea in Immunocompromised
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HIV:
Shigella
 Salmonella
 Campylobacter
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Acute Post-Transplant (w/in 6 mos)
CMV, CMV, CMV
 Giardia
 Cryptosporidium
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Shigella!
Shi sure is.
Invasive and Inflammatory Diarrhea
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Shigella
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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
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Salmonella
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Eggs, reptiles and amphibians, chickens, improperly treated
foods, Pizza Papalis in Mod 5, esp w. reptile toppings.
Typhoid (meaning “typhus-like”) fever:
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Relative bradycardia
Abdominal pain, borborygmi
Leukopenia with eosinophilia
Rash
Hepatosplenomegaly
+/- diarrhea
Vaccine
Trivia points: what causes typhus?
Campylobacter!
Invasive and Inflammatory Diarrhea
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Campylobacter
Most common bacterial squirtosis
 Most common route: fecal-oral
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 In
a perfect world, these two words would never
go together.
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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.
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Tales from the Cryptosporidium!
Cthulhu
Lives!
Cryptosporidium
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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
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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
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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
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Because you’ll kill them.
C. Difficile Be Difficile
Half of transplant patients who get Abx will
develop C. Diff enterocolitis.
 Full clinical spectrum:
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Uncomplicated diarrhea
 Enterocolitis
 Toxic Megacolon
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 Transplant
+ Diarrhea + Abdominal Pain = Xrays
Cyto Megatron Virus!
I DON’T FEEL
SO GOOD.
Megatron’s
diarrhea comes
out here.
CMV
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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:
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ganciclovir, valganciclovir, foscarnet, cidofovir
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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.
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Fecal-oral transmission.
Diarrhea, bloating, misery.
 TMP-SMX. Response varies.
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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.
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Pathogens from Another Galaxy!
Balantidium
Blastocystosis
GREETINGS,
EARTHLING. YOUR
BOWEL HABITS, AS
YOU HAVE KNOWN
THEM, ARE NOW OVER.
Encephalitozoon
Intergalactic Squirtosis
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Balantidium coli. Ciliated protozoan.
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Blastocystis hominis. Single-celled parasite (order
Blastocystida)
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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).
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Forms a multinucleate plasmodium in the host cell.
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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
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Can result in badness.
 Differential:
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 Infection
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GVH (BMT)
Std vs. Opportunistic spp.
 Antibiotic
effect
 Immunosuppressant effect
Organ Transplants
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Up to 6 months after transplant, or during
rejection or increased immunosuppression:
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Opportunistic and viral infections
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Giardia
Cryptosporidium
CMV
Isospora
Cyclospora
Microsporidium
Strongyloides
Organ Transplants
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After 6 months, if graft takes well:
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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
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ACUTE DIARRHEA IN HIV
DISEASE
50-90% of all AIDS patients.
 Multiple etiologies:
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Infectious
 Drug-related
 HIV enteropathy
 lymphoma, GI Kaposi’s
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Hydration, sample collection, strongly
consider admission, consult with ID.
ACUTE DIARRHEA IN HIV
DISEASE
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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).
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ACUTE DIARRHEA IN HIV DISEASE
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Drug-related
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Anti-retroviral therapy (all except Indinavir), especially
HAART (mitochondrial suppression with adenosinebased ARVs--check lactate)
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Antibiotic therapy
 Atovaquon
 Macrolides
 Ganciclovir, Foscarnet
 Antifungalls
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Post-antibiotic therapy
 C. Difficile
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Analgesics
 NSAIDS
 Narcotics (!)
ACUTE DIARRHEA IN HIV
DISEASE
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HIV/AIDS enteropathy
Severe, high-volume, watery diarrhea.
 Typically end-stage patients.
 No pathogen identified.
 Admission almost always required.
 Octreotide may help.
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Management
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ABCs!
A: Avoid introducing diarrhea into the airway.
B: Avoid breathing in the diarrhea.
C = replace that volume loss!
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Oral vs. IV
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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
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DISCHARGE CRITERIA:
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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.
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ADMISSION CRITERIA: Opposite of the discharge
criteria. Duh.
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ALWAYS discuss patient with primary if available;
arrange CLOSE follow up for discharged patients.
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No primary? STRONGLY consider admission
?
Gimme.
No good data. Sullydog approves, provided you
dilute to 1/3 with water.