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Recurrent Fever in the Pediatric Patient. Ping-Wei Chen Emergency Medicine Resident Much thanks to: Drs. Bryan Young, Graham Thompson, Susan Kuhn,Chris Waterhouse, Paivi Miettunen, Ron Anderson. +++ Concerned Parent. 4 year old boy 5 weeks of intermittent fevers (T max 38 9 C)

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recurrent fever in the pediatric patient

Recurrent Fever in the Pediatric Patient

Ping-Wei Chen

Emergency Medicine Resident

Much thanks to:

Drs. Bryan Young, Graham Thompson, Susan Kuhn,Chris Waterhouse, Paivi Miettunen, Ron Anderson

concerned parent
+++ Concerned Parent
  • 4 year old boy
  • 5 weeks of intermittent fevers (Tmax 389C)
    • last “a few days”
    • fatigue, malaise
    • Unsure if ever completely gone
    • ?red rash the first few days
  • Walk-in clinic x 2
    • “viral illness”
    • “the flu”
      • Negative urine dip
  • PLC ER
    • Today is visit #2
plc er visit 1
PLC ER Visit #1
  • CBC
    • Hgb 96
    • WBC 9.7
    • Plt 530
  • Electrolytes, Creatinine, BUN = normal
  • Urine dip, R+M negative
plc er visit 2
PLC ER Visit #2
  • “5 weeks intermittent fevers”
      • Tmax 389C
      • ✓ fatigue/malaise
      • Øvomiting, Ødiarrhea
      • Ørespiratory symptoms
      • Øgenitourinary symptoms
      • ✓red rash “first few days”
      • Øsick contacts
      • From Turkey 6 months ago
      • Preschool student
      • Previously healthy
      • Immunizations UTD

On exam

  • 379C, 100/65, 102bpm, 100% RAO2
  • HNT normal
  • CV normal
  • Resp – clear, equal BS
  • Abdo – soft, nontender
  • MSK – Ørash/joint pain
objectives
Objectives
  • Discuss definitions
    • Recurrent Fever/Periodic Fever
    • Fever of Unknown Origin (FUO)
  • Outline differential diagnoses
    • Regular VS Irregular fever intervals
  • Describe an approach
  • Expert opinion
    • ID, GI, Rheumatology, Oncology
working definition
Working Definition
  • Recurrent/Periodic Fever
    • Repeating episodes of fever separated by periods of normal temperature that return at regular or irregular intervals
  • Fever of Unknown Origin
    • Fever of greater than 3 weeks duration and uncertain diagnosis after 1 week of intensive investigation
recurrent fever
Recurrent Fever
  • John and Gilsdorf 2003
    • “≥3 episodes of fever in a 6 month periodwith no defined medical illness to explain the fever and with an interval of at least 7 days in between febrile episodes”
recurrent periodic fever
Recurrent/Periodic Fever
  • Long 2005
  • Recurrent Fever
    • “A single illness in which fever and other signs and symptoms wane and wax”
  • Periodic Fever
    • “Recurring episodes of illness for which fever is the cardinal feature…with intervening intervals of weeks to months of complete well-being. Episodes can have either clockwork or irregular periodicity”
fever of unknown origin
Fever of Unknown Origin
  • Petersdorf and Beeson 1961
    • “fever persisting more than 3 weeks in duration, with documented temperatures of 38.3oC on several occasions, and uncertain diagnosis after intensive study of at least 1 weeks duration”
etiology
Etiology
  • “Common disorders with uncommon presentations”
    • INFECTION
    • Inflammatory/Autoimmune
    • Undiagnosed (recurrent)/Neoplasms (FUO)
etiology2
Etiology

Ciftci et al. 2003

Pasic et al. 2006

Etiology FUO (n=185)

Infection 37.8%

Autoimmune 12.9%

Kawasaki Disease 6.4%

Malignancy 6.4%

Misc. 8.1%

Undiagnosed 30%

  • Etiology FUO (n=102)
    • Infection 44.2%
    • Collagen Vascular 6.8%
    • Malignancy 11.7%
    • Misc. 24.5%
    • Undiagnosed 12.8%
recurrent fever1
Recurrent Fever

Differential Diagnosis

Fever Intervals

Regular?

Irregular?

fevers at regular intervals
Fevers at Regular Intervals
  • Fever occurring at regular intervals
    • PFAPA syndrome*
    • Cyclic neutropenia
    • Relapsing fever (Borrelia spp. other than burgdorferri)
    • Undiagnosed cause*
  • Fever occasionally at regular intervals
    • Familial Mediterranean Fever
    • Hyper-IgD syndrome
    • EBV infection

John and Gilsdorf 2002

fever at regular intervals
Fever at Regular Intervals
  • Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenopathy (PFAPA)
    • high fever q21-28 days
    • Leukocytosis, ESR
    • well/investigations normal between episodes
    • Tx: prednisone, cimetidine
    • No long-term sequelae
fever at regular intervals1
Fever at Regular Intervals
  • Cyclic Neutropenia
    • Uncommon
    • May be clinically indistinguishable from PFAPA
    • Usually no bacterial infection during neutropenia
    • Diagnosis:
      • CBC X2-3/week for 6 weeks (ANC <500) and spontaneous recovery
      • Bone marrow
    • If symptomatic, G-CSF
fever at regular intervals2
Fever at Regular Intervals
  • Relapsing Fever
    • Spirochetes of Borrelia genus (not burgdorferi)
    • Fevers 1-6 days separated by 4-14 days
    • “crisis” (BP,HR) followed by profuse diaphoresis, falling temperature, and BP.
      • Mortality for untreated fever during crisis and its aftermath
    • Treatment: penicillin or tetracycline
fevers at irregular intervals
Fevers at Irregular Intervals

John and Gilsdorf 2002

an approach
An Approach
  • Careful history & physical exam
    • Establish pattern of fever (fever diary)
      • Constant VS Recurrent
      • Duration
      • Associated symptoms
    • Hematologic exam
      • Hepatosplenomegaly
      • Lymphadenopathy
when to refer
When to refer?
  • Dr. Susan Kuhn (Pediatric Infectious Diseases)
    • ≥3 episodes of recurrent fever
what to order
What to order?
  • Infectious Disease
    • Order:
      • CBC
      • Urine dip/R+M/C+S
      • Blood culture
      • ESR/CRP
      • EBV serology (IgM/IgG)
      • Quantitative immunoglobulins
    • Maybe:
        • CXRay – resp symptoms
        • Stool C+S/O+P – diarrhea
        • Thin/Thick blood smear – travel to endemic area ≤1 year
what to order1
What to Order?
  • Dr. Chris Waterhouse (Paediatric GI)
    • Add:
      • Hepatobiliary studies (ALT, GGT, ALP, lipase)
      • Iron studies (ferritin, iron)
      • Albumin (losses/decreased production)
      • Stool studies (C+S, O+P, C. diff)
what to order2
What to order?
  • Dr. Paivi Miettunen (Pediatric Rheumatology)
    • If referring directly to Rheumatology Clinic
      • Order:
        • CBC
        • Creatinine, Urea
        • ESR/CRP on days 1, 5, 10 of fever
        • Ferritin
        • IgD
        • Urine R+M
        • Urine Mevalonic Acid
what to order3
What to Order?
  • Dr. Ron Anderson (Pediatric Oncology)
    • Order:
      • CBC
      • CXRay
        • if lymphadenopathy, hepatomegaly, splenomegaly, abdominal mass
prognosis
Prognosis
  • Generally excellent
    • If no diagnosis after investigations
      • Fevers resolve
      • Growth/Development unaffected
    • No further testing unless new signs/symptoms
back to our case
Back to our Case
  • Referred to urgent paediatrics
    • Bloodwork/Urine investgations unremarkable
    • No diagnosis
      • Fevers resolved
    • Still being followed by paediatrics
conclusions
Conclusions
  • Recurrent Fever ≠ Fever of Unknown Origin
  • Differential Diagnosis are not the same
  • Urgent Paediatrics/Outpatient Paediatrics
  • Workup guided by ID/GI suggestions
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