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

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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

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PLC ER Visit 1

• CBC
• Hgb 96
• WBC 9.7
• Plt 530
• Electrolytes, Creatinine, BUN normal
• Urine dip, RM negative

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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

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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

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Definitions
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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

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Recurrent Fever

• John and Gilsdorf 2003
• 3 episodes of fever in a 6 month period with no
  defined medical illness to explain the fever and
  with an interval of at least 7 days in between
  febrile episodes

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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 featurewith intervening intervals
  of weeks to months of complete well-being.
  Episodes can have either clockwork or irregular
  periodicity

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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

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Throw me a frickin bone here
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Etiology

• Common disorders with uncommon presentations
• INFECTION
• Inflammatory/Autoimmune
• Undiagnosed (recurrent)/Neoplasms (FUO)

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Etiology
Infectious Autoimmune/Inflammatory Malignant No diagnosis Misc
McClung 1972 (n99) 28 14 8 11 16
Pizzo et al. 1975 (n100) 52 20 6 12 10
Feigen and Shearer 1976 (n20) 35 20 5 30 10
Lohr and Hendley 1977 (n54) 33 21 13 19 15
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Etiology

• Ciftci et al. 2003

• Pasic et al. 2006

• Etiology FUO (n102)
• Infection 44.2
• Collagen Vascular 6.8
• Malignancy 11.7
• Misc. 24.5
• Undiagnosed 12.8

• Etiology FUO (n185)
• Infection 37.8
• Autoimmune 12.9
• Kawasaki Disease 6.4
• Malignancy 6.4
• Misc. 8.1
• Undiagnosed 30

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Recurrent Fever

• Differential Diagnosis
• Fever Intervals

Regular?
Irregular?
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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
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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

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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 lt500) and
  spontaneous recovery
• Bone marrow
• If symptomatic, G-CSF

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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

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Fevers at Irregular Intervals
John and Gilsdorf 2002
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An Approach

• Careful history physical exam
• Establish pattern of fever (fever diary)
• Constant VS Recurrent
• Duration
• Associated symptoms
• Hematologic exam
• Hepatosplenomegaly
• Lymphadenopathy

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When to refer?

• Dr. Susan Kuhn (Pediatric Infectious Diseases)
• 3 episodes of recurrent fever

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What to order?

• Infectious Disease
• Order
• CBC
• Urine dip/RM/CS
• Blood culture
• ESR/CRP
• EBV serology (IgM/IgG)
• Quantitative immunoglobulins
• Maybe
• CXRay resp symptoms
• Stool CS/OP diarrhea
• Thin/Thick blood smear travel to endemic area
  1 year

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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 (CS, OP, C. diff)

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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 RM
• Urine Mevalonic Acid

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What to Order?

• Dr. Ron Anderson (Pediatric Oncology)
• Order
• CBC
• CXRay
• if lymphadenopathy, hepatomegaly, splenomegaly,
  abdominal mass

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Prognosis

• Generally excellent
• If no diagnosis after investigations
• Fevers resolve
• Growth/Development unaffected
• No further testing unless new signs/symptoms

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Back to our Case

• Referred to urgent paediatrics
• Bloodwork/Urine investgations unremarkable
• No diagnosis
• Fevers resolved
• Still being followed by paediatrics

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Conclusions

1. Recurrent Fever ? Fever of Unknown Origin
2. Differential Diagnosis are not the same
3. Urgent Paediatrics/Outpatient Paediatrics
4. Workup guided by ID/GI suggestions