Recurrent fever in the pediatric patient
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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

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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


Definitions

Definitions


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”


Throw me a frickin bone here

“Throw me a frickin’ bone here”


Etiology

Etiology

  • “Common disorders with uncommon presentations”

    • INFECTION

    • Inflammatory/Autoimmune

    • Undiagnosed (recurrent)/Neoplasms (FUO)


Etiology1

Etiology


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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