A practical approach for evaluating PUO in paediatrics.

1. PYREXIA OF UNKNOWN
ORIGIN

2. Answer this:
The commonest cause of PUO is:
a) A common disease presenting in atypical way.
b) A rare disease presenting in atypical way.
c) A common disease presenting typically.
d) A rare disease presenting typically.
 The answer is ..A

3. Normal Body Temperature
 The hypothalamus is the heat-regulating center of the body
and helps in maintaining a stable body temperature.
 The normal body temperature ranges from 37.0 degree C
and 37.5 degree C with evening temperatures being 0.5-1.0
degree C higher than in the morning.
 Oral temperature is about 0.4 degree C below as compared
to rectal temperature and axillary temperature is about 1
degree C below rectal temperature.
 In infants and young children, a rectal temperature with a
glass- mercury or digital-electronic thermometer is
considered the gold standard for taking temperatures.

4. How to define fever
clinically?
 Persistent elevation of body temperature
above the normal levels in an individual.
 The child has fever if:
o Rectal temperature >100.4 degrees F (38 C)
o Oral temperature >99.7 degrees F (37.6 C)
o Axillary temperature >99 degree F (37 C)

5. Type of fever (fever patterns)
 Intermittent fever - Fever that touches normal for a few
hours during the day. It is seen in malaria, acute
pyelonephritis, local boils and furuncles.
 Remittent fever - Fever that fluctuates more than 1.5
degree F in 24 hours without touching normal.
 Continuous fever - Fever that does not touch normal and
fluctuates less than 1.5 degree F in a day. It is seen in
enteric fever, Bacterial endocarditis, viral pneumonia.

6.  A&B-Continuous fever
 C-Remittent
 D-Intermittent
 E-Relapsing fever
 F-Undulant fever

7. Liebermeister's rule
 The pulse rate rises about 15 beats/min for
each degree centigrade of fever

8. Causes of Relative
Bradycardia.
 Factitious fever
 Drug fever
 Legionnaires disease
 Psittacosis
 Typhoid fever (Faget's sign)
 Mycoplasma pneumonia
 Brucellosis
 Dengue
 Yellow fever
 Tuberculous meningitis
 Blackwater fever (Falciparum malaria with profound
hemolysis)

9. Fever with Eponyms
 Pontiac fever---  Legionella pneumophila
 Shanghai fever---  Pseudomonas
 Brazilian purpuric fever---(pink  Hemophilus aegyptius
eye)
 Havernhill fever---  Streptobacillus monoliformis
 Oroya fever---  Bartonella bacilliformis
(Carrion's d/s)
 Q fever---  Coxiella burnetti
 Colorado tick fever---  Orbivirus
 Trench fever---  Rochalimaea quintana
(five day fever)
 Monkey fever -  Kayasanur forest disease
 Glandular fever -  IMN (EBV)
 Goal Fever -  R. prowazaki

10. PUO: Terminolgy
 Petersdorf and Beeson Criteria
 Old Definition:
1. Fever higher than 38.3oC on several occasions.
2. Duration of fever – 3 weeks
3. Uncertain diagnosis after one week of study in
hospital
 New Definition:
 Eliminated the in-hospital evaluation requirements
→ 3 outpatient visits, or 3 days in hospital. …
Ambulatory as well as in hospital

11. Definition Expansion
Durack and Street Classification
1. Classical PUO
2. Nosocomial PUO
3. Neutropenic PUO
4. HIV-Associated
5. Transplant

12.  Nosocomial PUO in hospital patients with fever of 38.3°C on several
occasions caused by a process not present or incubating on admission
where initial cultures are negative and diagnosis unknown after 3 days'
investigation.
 Neutropenic PUO includes patients with fever as above with <1 x
109 neutrophils with initial negative cultures and diagnosis uncertain
after 3 days.
 HIV-associated PUO includes HIV-positive patients with fever as
above for 4 weeks as outpatients or 3 days as inpatients, with an
uncertain diagnosis after 3 days' investigation where at least 2 days
have been allowed for cultures to incubate.

13. Bacterial vs Viral fevers
Bacterial Viral
 Leukocytosis  Uncommon
 Shift to left  Uncommon
 High grade fever  Low grade fever
 Neutropenia  uncommon
 Raised ESR and CRP  Uncommon
 Response to antibiotics  Usually self limiting

14. Common causes of FUO
 The causes are subdivided into 4 categories:
o (1) infectious diseases, (40-60%)
o (2) autoimmune diseases, (10-20%)
o (3) malignancies, and
o (4) miscellaneous.
o Children younger than 6 years are most likely to have FUO
resulting from an infection; autoimmune diseases start to
become more common after 6 years, although infection
remains the most frequent cause of FUO

15. FUO: Etiology: Bacterial
 Bacterial endocarditis  Pyelonephritis
 Bartonellosis  Salmonellosis
 Brucellosis  Sinusitis
 Chlamydia  Subdiaphragmatic abscess
 Lymphogranuloma  Tuberculosis
venereum  Tularemia
 Psittacosis
 Q fever
 Leptospirosis
 Rickettsial diseases
 Liver abscess
 Q fever
 Mastoiditis (chronic)
 Rocky Mountain spotted
fever

16. Viral & Fungal Etiology
 Cytomegalovirus  Malaria
 Epstein-Barr virus  Sarcoidosis
(infectious  Toxoplasmosis
mononucleosis)  Visceral larva migrans
 Hepatitis viruses  Visceral leishmaniasis
 Blastomycosis
(nonpulmonary)
 Histoplasmosis
(disseminated)

17. Autoimmune and malignancy
 Polyarteritis nodosa
 Systemic idiopathic juvenile arthritis
 Systemic lupus erythematosus
 Hodgkin disease
 Leukemia or lymphoma
 Neuroblastoma

18. Drug Fever
 Pharmacologic action of the drug (e.g., Jarish–Herxheimer
reaction, tumor cell necrosis with chemotherapeutic agents
 Drug's effects on thermoregulation (e.g.,MOA inhibitors)
 Drug Administration–Related Fever (e.g.,Amphtericin B,
Bleomycin)
 Fever Related to Pharmacologic Action of the Drug (e.g., Jarisch-
Herxheimer reaction)
 Idiosyncratic Reactions (Malignant hyperthermia,NMS)
 Hypersensitivity (e.g., penicillin, methyldopa, quinidine)

19. Approach to PUO:History
 Specifics of the history should include the following:
 • Duration and characteristics of the fever (number of spikes per day,
timing of the temperature elevation, whether the temperature returns to
normal or below normal)
 • Travel history or exposure to people who have traveled to regions
endemic for particular diseases (typhoid, malaria, tuberculosis, RMSF)
 • Exposure to any animals (cat-scratch disease, rat-bite fever,
leptospirosis)
 • Exposure to unpasteurized dairy products (brucellosis)
 • Presence of rashes, conjunctivitis, mucous membrane changes, and
arthritis (juvenile arthritis, Kawasaki syndrome, SLE)
 • Presence of associated cough, weight loss, or lymphadenopathy
(lymphoma, leukemia, neuroblastoma)

20. Physical Examination
 Rectal temperature, respiratory rate, heart rate, and blood pressure
measurements should be obtained.
 Inspection of the pharynx for hyperemia and exudate, of the tympanic
membranes for chronic otitis media, transillumination of the sinuses for
sinusitis, a search for a purulent nasal discharge, and auscultation of the chest
for localized wheezing are all important.
 In the older child, an examination of the teeth to exclude dental caries and
periodontal disease should be included. A new cardiac murmur may be a clue
to rheumatic fever or infective endocarditis.
 Lymphadenopathy, especially if generalized, may suggest a viral infection,
such as infectious mononucleosis, cytomegalovirus infection, toxoplasmosis, or
HIV infection.
 Joints must be examined meticulously for swelling, restricted range of motion,
and tenderness. Skin rashes may suggest a viral disease or an autoimmune
disease such as juvenile idiopathic arthritis.

21. Interesting Scenarios
 Repeated fevers,absence of tears,smooth tongue: Riley-Day syndrome
 fever cycle periodicity as multiples of 7 days, that is, most commonly at
21 or 28-day intervals:Cyclical Neutopenia
 Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS):
The syndrome is characterized by recurrent attacks of fever, typically
occurring every 4 to 8 weeks. Febrile episodes last about 5 days and can
be associated with cervical lymphadenopathy, abdominal pain, and
headache.
 Periodic fever, aphthous stomatitis, pharyngitis, and cervical
adenopathy (PFAPA): characterized by periodic episodes of high fevers
lasting 3 to 6 days with recurrence every 21 to 28 days

22. Investigations:Level 1
 Sedimentation rate
 • Complete blood count with differential (evaluation for anemia,
thrombocytopenia, presence of blasts)
 • Metabolic panel, including BUN, creatinine, liver function tests,
lactate dehydrogenase, and uric acid levels
 • Urinalysis and urine culture
 • Chest x-ray and tuberculin skin test
 • Epstein-Barr virus and cytomegalovirus serology
 • Viral culture of the nasopharynx and eyes (if clinically
warranted)

23. Level 2
 Echocardiogram. Evaluate for coronary artery brightness or
aneurysms associated with Kawasaki disease and pericardial
effusion associated with various rheumatologic conditions,
including SLE.
 Abdominal or pelvic computed tomography. Detection of
occult abscesses or granulomatous lesions
 Bone scan. Evaluation for occult osteomyelitis or discitis
 Serology. As clinically indicated by history or physical exam
 ANA, double-stranded DNA, compliment levels (if history or
physical suggests SLE)

24. Level 3
 Bone marrow aspiration, looking for infiltrative process
or to culture a variety of organisms (such as brucellosis,
tuberculosis, or disseminated fungal infection).
 • Biopsy of suspicious skin lesions or lymph nodes.
 • Endoscopy and biopsy

25. Recap points:
 Petersdorf & Beeson
criteria
 Durrack & Street
classification
 Think common etiologies
first
 Examination and
investgations based on
the history

26. References
1. Nelson Textbook of Pediatrics, 18th ed. Chapter:175
2. Sarah S.Long Principles and Practice of Pediatric infectious
diseases: 114-122
3. Mendel Douglas Principles and Practice of Pediatric infectious
diseases: 536-549
4. Clinical Methods: The History, Physical, and Laboratory
Examinations. 3rd edition.Walker HK, Hall WD, Hurst
JW:Chapter 211
5. AAP Textbok of Pediatric care: Chapter 182
6. Pediatric infectious disease secrets By Joel D. Klein, Theoklis E.
Zaoutis: Chapter 36.