Rat Bite Fever – 10/23/18

Thanks to Joe for presenting the fascinating case of a middle-aged man who presented with AMS and SIRS, found to have a LP findings concerning for aseptic/viral meningitis with a negative work up and persistent fevers, eventually found to have a swollen joint which was tapped and synovial fluid sample sent for 16s rDNA showing streptobacillus moniliformis, also known as Rat Bite Fever!


Clinical Pearls

  • The predominant cell type found in CSF of patients with viral or aseptic meningitis is monocytes and PMNs
  • Traumatic LPs result in blood seeping into the CSF fluid sample.  To correct for a traumatic LP, subtract 1 WBC for every 1000 RBCs in the tube.
  • Most common causes of aseptic meningitis are enteroviruses (Coxsackievirus and echovirus).
  • Most common cause of proven viral encephalitis in the US is West Nile Virus (remember that it presents with flaccid paralysis first and is often confused for GBS).
  • The most commonly used OTC medications associated with aseptic meningitis are NSAIDs.
  • While >90% of rodents are estimated to carry streptobacillus moniliformis (bacteria causing Rat Bite Fever), rate of transmission to humans after a bite is ~10%.
  • Streptobacillus moniliformis does not grow on routine cultures.  16s rDNA gene sequencing (AKA universal PCR) can be sent on synovial fluid or tissue to establish the diagnosis.

CSF fluid findings in various diseases

Capture

Figure above adapted from the UpToDate and the UCSF Hospitalist Handbook.

Fever of unknown origin (FUO): Our patient did not meet this definition, but just for review

  • Defined as T >38.3 on several occasions over 3 weeks and failure to diagnose after 3 days of hospitalization or three outpatient visits
  • Etiologies
    • Infectious (~1/3): intra-abdominal, abscesses (dental, pelvic), culture-negative endocarditis, TB, lyme, C diff, prostatitis, EBV, CMV, HIV
    • Autoimmune (~1/3): Still’s, seronegative spondy, lupus, cryo, PAN, GPA
    • Malignancy (~20%): lymphoma, leukemia, sarcoma, mets, MDS, pancreatic, colon, RCC
    • Other: drug reaction, alcoholic hepatitis, ETOH w/d, toxic ingestion, central or factitious fever
    • Undiagnosed (~20%)
    • Nosocomial: PE, line infection, transfusion related, C diff, drug fever

Rat Bite Fever (RBF)

  • Epidemiology
    • Only 17 cases between 2000 and 2012 identified in California
    • Many cases go undiagnosed since it’s not a nationally notifiable disease and b/c the bacteria responds to empiric antibiotic therapy.
    • Risk of getting the infection after a rate bite is 10% (20,000 rat bites occur in the US/year)
    • At risk populations are pet store workers, lab techs, and people living in poverty
    • Fun fact: in Asia, RBF is known as sodoku.
  • Micro
    • Streptobacillus moniliformis is the most common cause in the US
    • Pleomorphic fastidious branching gram negative bacillus
      • Stains irregularly so can be mistaken for gram positive
    • Bacteria require specific media for isolation and incubation in a high CO2 environment
    • Grows slowly so if suspicious, hold onto cultures for at least 7 days
  • Transmission:
    • Found in the nasal and oropharyngeal flora of rats and other rodents that are asymptomatic.  High rate of carriage.
    • Can result from bite or scratch or from ingestion of food or water contaminated with infected rat feces (latter is called Haverhill Fever, named after town in Massachusetts where the illness developed after consumption of contaminated unpasteurized milk)
  • Clinical manifestations:
    • Ranges from mild flu-like illness (more common) to fulminant sepsis in children and adults
    • Mortality is 13% in untreated patients
    • Incubation period is <7 days
    • Abrupt onset of fever, myalgias, migratory arthralgias (typically of the knees but can go to elbows, wrists, shoulders, and hips as well), vomiting, pharyngitis, and headache
    • Bite wound has usually resolved by the time of presentation
    • No regional adenopathy
    • Can be accompanied by a maculopapular rash on extensor surfaces and palms/soles
    • Vomiting and pharyngitis are more common with ingestion
    • Arthritis may relapse or persist for years and sometimes pathogenic bacteria can persist in joints for months despite clearance of the organism from blood and other sites.
  • Complications
    • Bacteremia
    • Meningitis (as with our patient)
    • Endocarditis
    • Myocarditis
    • Pneumonia
    • Focal abscesses
    • Septic arthritis (as with our patient)
    • Multiorgan failure
  • Diagnosis
    • No serologic test is available
    • Analysis of 16s rDNA gene sequence has been used for diagnosis on appropriate specimens
      • Not available for blood but can be done on synovial fluid or tissue.
    • Dx is empirically made in patients with unexplained febrile illness or sepsis and a history of rat exposure, especially if relapsing or intermittent fever pattern and joint involvement.
  • Treatment
    • PCN
    • No good studies on the disease to help us determine duration because of paucity of cases
    • For severe cases, treatment mimics endocarditis
  • Prevention:
    • Avoid rats
    • If rat bite, then give a three-day course of oral PCN V 500 mg QID.  Efficacy of this approach however is unknown

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