Download 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
• 4 year old boy
• 5 weeks of intermittent fevers (Tmax 389C)
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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
• CBC
– Hgb 96
– WBC 9.7
– Plt 530
• Electrolytes, Creatinine, BUN = normal
• Urine dip, R+M negative
PLC ER Visit #2
• “5 weeks intermittent
fevers”
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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
• 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
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
• 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”
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
• 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”
Etiology
• “Common disorders with uncommon
presentations”
1. INFECTION
2. Inflammatory/Autoimmune
3. Undiagnosed (recurrent)/Neoplasms (FUO)
Etiology
Infectious Autoimmune/I
nflammatory
Malignant
No diagnosis
Misc
McClung
1972
(n=99)
28%
14%
8%
11%
16%
Pizzo et al.
1975
(n=100)
52%
20%
6%
12%
10%
Feigen
and
Shearer
1976
(n=20)
35%
20%
5%
30%
10%
Lohr and
Hendley
1977
(n=54)
33%
21%
13%
19%
15%
Etiology
Ciftci et al. 2003
• Etiology FUO (n=102)
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Infection 44.2%
Collagen Vascular 6.8%
Malignancy 11.7%
Misc. 24.5%
Undiagnosed 12.8%
Pasic et al. 2006
• Etiology FUO (n=185)
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Infection 37.8%
Autoimmune 12.9%
Kawasaki Disease 6.4%
Malignancy 6.4%
Misc. 8.1%
Undiagnosed 30%
Recurrent Fever
Differential Diagnosis
Fever Intervals
Regular?
Irregular?
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
• 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 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 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
John and Gilsdorf 2002
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?
• Dr. Susan Kuhn (Pediatric Infectious Diseases)
• ≥3 episodes of recurrent fever
What to order?
• Infectious Disease
– Order:
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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 Order?
• Dr. Chris Waterhouse (Paediatric GI)
– Add:
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Hepatobiliary studies (ALT, GGT, ALP, lipase)
Iron studies (ferritin, iron)
Albumin (losses/decreased production)
Stool studies (C+S, O+P, C. diff)
What to order?
• Dr. Paivi Miettunen (Pediatric Rheumatology)
– If referring directly to Rheumatology Clinic
• Order:
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CBC
Creatinine, Urea
ESR/CRP on days 1, 5, 10 of fever
Ferritin
IgD
Urine R+M
Urine Mevalonic Acid
What to Order?
• Dr. Ron Anderson (Pediatric Oncology)
– Order:
• CBC
• CXRay
– if lymphadenopathy, hepatomegaly, splenomegaly, abdominal
mass
Prognosis
• Generally excellent
– If no diagnosis after investigations
• Fevers resolve
• Growth/Development unaffected
– No further testing unless new signs/symptoms
Back to our Case
• Referred to urgent paediatrics
– Bloodwork/Urine investgations unremarkable
– No diagnosis
• Fevers resolved
– Still being followed by paediatrics
Conclusions
1.
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Recurrent Fever ≠ Fever of Unknown Origin
Differential Diagnosis are not the same
Urgent Paediatrics/Outpatient Paediatrics
Workup guided by ID/GI suggestions