Neutropenia and Acute Diarrhea… It’s not C.diff, it’s Norovirus (11/28/18)

Elise presented a case of a middle age man with recently diagnosed pancreatic adenocarcinoma on chemo presenting with acute loose watery stools (“too many to count”) and abdominal discomfort. He appeared septic on presentation and was found to be neutropenic. Unfortunately (or fortunately) it is not the typical C.diff colitis, but actually norovirus!


Acute Diarrhea

Definition: defined as watery stool 3x in 24 hours, < 14 days duration

Most are infectious in etiology in an acute setting

Other causes: Ingested osmoles, malabsorption

Clues

  • Secretory: High volume, watery, no systemic symptoms, usually due to small intestinal involvement
    • Most common causes are viral (rota and noro), enterotoxin, ETEC, or vibrio chlolarae.
    • Negative fecal WBC
  • Invasive: Smaller volume, bloody/mucoid, tenesmus + LLQ pain, systemic symptoms.
    • Site of involvement is the colon. Common causes are Shigella, Campylobacter, EHEC, Entamoeba histolytica
    • Positive fecal WBC
  • Importance of vomiting: Usually indicates the ingestion of a pre-formed toxin or a viral infection. Examples:
    • Staph aureus
    • B. cereus
    • Norovirus
    • Certain parasites

Non-bloody/Watery

  • Norovirus (very common)
  • Rotavirus, enteric adenovirus, astrovirus (usually in immunocompromised adults)
  • diff (can be bloody/inflammatory)
    • Nosocomial vs community acquired
  • Clostridium perfringens (2nd most common cause of foodborne bacterial infection)
    • Associated with outbreaks in restaurants and catering facilities
    • Usually mild symptoms.
    • Associated with improperly cooked or stored meat.
    • Self-limited, supportive care often suffices
  • Enterotoxigenic E.coli (ETEC): AKA traveler’s diarrhea
    • Cruise ships, foreign countries, fecal contimation or food or water from an infected person.
  • Giardia lamblia:
    • Water & food borne outbreaks
    • Sx: 7-14 days incubation post exposure.
    • Presentation: Foul smelly stools, cramps, bloating.
    • Tx: Supportive + Metronidazole, Tinidazole, albendazole
  • Cryptosporadium
    • One of the most common parasitic foodborne diarrhea
    • Endemic in cattle, usually transmitted via infected animal or person. Food/water borne outbreaks also common.
    • Presentation: Severe, dehydrating watery diarrhea but self-limited in immunocompetent hosts.
    • Immunocompromised: More severe
  • Other bacterial
    • Staph aureus, Bacillus cereus: enterotoxins, acute diarrhea + vomiting
    • Listeria monocytogenes: Can cause systemic symptoms/spread
    • Cyclospora: Associated with sporadic outbreaks due to imported raspberries and basil.
    • Aeromonas: Distributed in watery environments, suspect if contact with fresh or brackish water.
  • Other viral: Hepatitis A

Inflammatory: bloody or mucoid diarrhea, with associated fever, abd pain. Presence of inflammatory cells in the stool. More likely bacterial.

  • Salmonella: Nontyphoidal, leading cause of acute inflammatory diarrhea
    • Association: Poultry, eggs, milk products, animal contacts
    • Incubation: 8 – 72 hours
    • Presentation: diarrhea is usually non-bloody, N/V, fever.
  • Campylobacter
    • Undercooked poultry
    • Watery or hemorrhagic diarrhea, 2-5 days after exposure
    • Association: Guillain-Barre, reactive arthritis
  • Shigella: Dysenteric diarrhea
    • Colonic infection, person to person or fecal oral transmission.
    • Mucoid or bloody diarrhea, 3-7 days after exposure.
  • EHEC: Enterhemorrhagic E.coli
    • Association: HUS
    • Presentation: Watery/progressively bloody diarrhea, 3-4 days post exposure, abd pain + fever.
  • Yersinia
    • Uncommon, can be transmitted via undercooked pork, unpasteurized milk, fecally contaminated water. 1-14 days after exposure
    • Associated with concurrent pharyngitis.
  • Others: Entamoeba histolytica, noncholera vibrios, CMV, HSV
    • CMV & HSV: Dx has to be confirmed by biopsy. Suspect these in immunocompromised patients.

Neutropenia and GI symptoms

Neutropenic enterocolitis (typhilitis), cytotoxic agent-related diarrhea, any viral/bacterial infection, but for typhilitis specifically:

Epidemiology

  • Associated with hematologic malignancies or ingestion of food contaminated with C. perfringens
  • Pre-existing bowel wall abnormalities increases risk (i.e. diverticulitis, tumor, previous surgery).

Pathophysiology

  • Infection of the bowel wall, usually the cecum but can involve ascending colon & ileum, leading to tissue necrosis

Presentation

  • Neutropenic
  • Fever, mean of 3 weeks after cytotoxic chemo
  • Abd pain, distension, N/V, watery/bloody diarrhea
  • Usually RLQ pain, can mimic appendicitis.

Diagnosis

  • CT

Management

  • 4th gen cephalosporins i.e. cefepime + Flagyl, surgery is generally avoid but indicated if e/o perforation

Prognosis

  • 50% mortality

Norovirus

Epidemiology:

  • Most common viral cause of gastroenteritis worldwide, all age range affected
  • 19-21 million cases every year in the US
  • Unclear reason, peak incidence during winter months.
  • Food born outbreaks is common: leafy greens, fruits, shell fish.

Pathophysiology/Transmission

  • Fecal oral transmission, RNA virus
  • Different genotypes exist with further sub-groups, tend to have a preference for certain blood type.
  • Incubation: 24-48 hours, affects the small intestines
  • Very infectious, can cause full blown infection even if exposed to a small amount (< 100 viral particles)
  • Extremely stable in the environment, resists freezing or heating up to 60 degrees C, disinfection requires chlorine or EtOH
  • Viral shedding is max over the first 24-48 hours, and pts can continue to shed for up to weeks

Presentation

  • Duration: 48-72 hours
  • Watery diarrhea, N/V, abd pain.
  • Vomiting usually prominent
  • Usually self-limiting but can be severe in immunocompromised patients

Diagnosis

  • Stool PCR

Management

  • Supportive
  • Contact plus isolation
  • Notify infection control (contact plus isolation)
  • If you have been exposed to someone with norovirus and you are symptomatic, PLEASE CALL IN SICK since this illness is highly contagious. Notify us and employee health. You have to be asymptomatic for at least 48 hours, and you have to be cleared by employee health, prior to returning to work.

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