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