Diarrhea Part II: The Immunosuppressed Patient

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Diarrhea Part IIThe Immunosuppressed Patient

• Jonathon Sullivan MD, PhD
• Dept of Emergency Medicine
• Wayne State University

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FOR SOME WEIRD REASON

• Ayesha thinks I know more about this than you do.
  
• Disclaimer follows.

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(No Transcript)
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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 HIVAcute Diarrhea

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REVIEW OF BASIC SQUIRTOLOGY

• A quick reprise of some of the high (and low)
  points of Diarrhea Part I.

rmber Me?
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Causes of Morbidity and Mortality

• Dehydration, Dehydration, Dehydration
• Electrolyte depletion and malnutrition
• Bacteremia/Sepsis
• Perforation, megacolon
• Underlying condition

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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

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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.
• Toxins
• Viral damage
• 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

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

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Or, If You Prefer, These 4 Flavors
lumps together invasive, inflammatory,
non-amebic dysenteries, etc.
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Invasive vs. Noninvase
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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

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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

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OUR CAST OF CHARACTERSaka The Bug Parade

• Three Categories
• The Usual Suspects
• Crass Opportunists
• Pathogens From Another Galaxy

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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

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Opportunistic Pathogens

• Cyto Megaton Virus
• Adenovirus
• 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

• HIV
• Shigella
• Salmonella
• Campylobacter
• Acute Post-Transplant (w/in 6 mos)
• CMV, CMV, CMV
• Giardia
• Cryptosporidium

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Shigella!
Shi sure is.
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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)

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Dont Confuse Them
Salmonella
Sal Mineo
Treatment Required
No Treatment
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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?

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Campylobacter!
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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 tastesjust like
  chicken.
• Associated with HUS, TTP, and Guillan-Barre (!)

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Backpackers Beware!
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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!
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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.

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Amy!
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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.

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Si, Difficile!
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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 youll kill them.

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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

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Cyto Megatron Virus!
I DONT FEEL SO GOOD.
Megatrons diarrhea comes out here.
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CMV

• AKA Human Herpesvirus 5 or HCMV
• 50-80 of the population has a-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.

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Isospora!
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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.

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Cyclospora!
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Cyclospora cayetanensis

• Related to Isospora spp.
• Frequent cause of travellers 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
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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 dont have to know exactly what this means to
  know you dont like it.
• Just weird. Dont 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!
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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

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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

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Organ Transplants

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

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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, OP
• 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
• Infectious
• Drug-related
• HIV enteropathy
• lymphoma, GI Kaposis
• Hydration, sample collection, strongly consider
  admission, consult with ID.

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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).

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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 (!)

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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.

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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.

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ACUTE DIARRHEA
ASSESS FOR PERF (THINK S. TYPHII)
LAB CBC, LYTES, CD4, OP, 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
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ACUTE DIARRHEA HIV ABD PAIN AND/OR FEVER
ADMIT
HYPOTENSION ACUTE ABD NO POS?
O P POSITIVE?
N
Y
N
Y
TENESMUS OR BLOODY STOOL?
BLOATING OR FLATULANCE?

• FREAK OUT
• CALL SURG
• IVFs ARE GOOD.
• THINK SAL, SHIG AND S. TYPHII
• CEFTRIAX FLAGYL OR CIPRO
• XRAYS
• EGDT IF NEC

Y
N
Tx FOR SAL, SHIG, CAMPY, YERS. BACTRIM or CIPRO
14d
TX FOR COCCIDIA, etc. BACTRIM 14d
Y
N
TREAT FOR AMY THE AMEBA FLAGYL
TREAT FOR GIARDIA FLAGYL
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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

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Gimme.
No good data. Sullydog approves, provided
you dilute to 1/3 with water.