Post on 17-Dec-2015
Recurrent Fever in the Pediatric Patient
Ping-Wei ChenEmergency 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)– 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”• 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. INFECTION2. Inflammatory/Autoimmune3. Undiagnosed (recurrent)/Neoplasms (FUO)
EtiologyInfectious Autoimmune/
InflammatoryMalignant 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)
– Infection 44.2%– Collagen Vascular 6.8%– Malignancy 11.7%– Misc. 24.5%– Undiagnosed 12.8%
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%
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:
• 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:• 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:
– 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. Recurrent Fever ≠ Fever of Unknown Origin2. Differential Diagnosis are not the same3. Urgent Paediatrics/Outpatient Paediatrics4. Workup guided by ID/GI suggestions