This document defines fever of unknown origin and outlines the process for evaluating a patient with prolonged or recurrent fever when the cause is not readily apparent. It discusses taking a thorough history including fever characteristics, travel, exposures, medications and symptoms. A full examination focuses on potential infectious sources or underlying conditions. Initial tests include blood counts, inflammation markers and cultures, with further imaging and specialty-guided biopsies as needed to identify treatable causes. Empiric antibiotics may be used selectively while avoiding overuse before a pathogen is identified. Referrals to specialists can help determine causes like inflammatory diseases or infections requiring their management.

1. PUO Guideline by
Dr A Abdurrazaq

2. Definition :
Fever of unknown origin refers to the presence of a
documented fever for a specified time, for which a
cause has not been found after a basic medical
evaluation.

3. History
Fever:
-Thermometer used ,
- its type,
- factitious,
- site ,
- core or peripheral

4. Pattern:
 Continuous:
Temperature remains above normal throughout
the day and does not fluctuate more than 1 °C
in 24 hours (meningitis, encephalitis, Lobar
pneumonia, typhus fever).

5.  Remittent:
Temperature remains above normal throughout
the day and fluctuates more than 1 °C in 24 hours
( Endocarditis,brucellosis).

6.  Intermittent:
Temperature elevation is present only for a
certain period, later cycling back to normal (
Tertian fever in Plasmodium vivax , ovale &
falciparum. Quartan fever in P. malariae, TB ,
JIA ),

7. Another class of intermittent fever is
Pel-Ebstein fever weeks high for one week
and low for the next week and so on

8.  Undulant Fever:
Rising & falling like a wave (Brucellosis)

9.  Cyclical fever:
usually every 3 weeks
(cyclic neutropenia & Hyper IgD ).

11. Height & Duration:
Temperature below 38.5 intermittent is usually due to
Viral infection .Temperature above 40 is a pediatric
emergency.(Infectious causes: septicaemia,ruseola,
measles. Non infectious: Kawasaki disease, malignant
hyperthermia, drug fever ,rarely intracranial Hge).

12. Response to:
paracetamol and or NSAID
(no response: dysautonomia)

13. Associated symptoms:
 Nasal discharge(Sinusitis),
 Red eyes(Kawasaki ),
 GI ( IBD ,Salmonella,Abcesses), Recurrent
pharyngitis with ulcers ( Periodic fever) in people
of Mediterranean origin (FMF),
 Salmon rash only during fever (JIA),
 Limb pain (leukaemia, osteomyelitis,JIA

14. Other part of the history:
History of travel to TB-endemic region (Pakistan,India,china
,Nigeria,) Malaria endemic regions (central & south America, Haiti,
Africa).
Prophylaxis & immunization
History of contact with cat, sheep, dog, monkey
o Bites (tick: arbovirus, malaria)
o Meat: undercooked (brucella,toxoplasma, hepatitis)
o Pica (visceral larva migrans, toxoplasmosis)

15.  Drug history:
All including non -prescription (Drug fever),
Antibiotics eg cephalosporin, penicillin, Phenytoin can
all cause drug fever.
 Ethnicity:
Sephardic Jew, Armenian, Turkish, Arab (Familial
Mediterranean Fever), Ashkenazi Jew (Riley-Day
Syndrome).

16. Examination:
ENT:
o Sinuses
o Lymphadenopathy (Malignancy, EBV, CMV)
o Red, no exudates (EBV)
o Dental abscess
o Conical teeth (ectodermal dysplasia)
o Smooth tongue (dysautonomia)
o Gum hypertrophy, tooth loss(leukaemia, histiocytosis).

17. Eyes:
o Conjunctivitis
o palpebral (infectious mononucleosis)
o bulbar (Kawasaki) ,Phlyctenular (TB)
o Retinopathy (PAN, miliary TB, toxoplasmosis, vasculitis)
o Pupil dilation (hypothalamic or autonomic dysfunction)

18. Skin
o Rash only during fever (JIA)
o No sweat (familial dysautonomia)
o Petechiae (endocarditis, rickettsia)
o Papules (cat scratch)
o Eschar (tularaemia)
o Erythema migrans (Lyme)
o Malar (SLE)
o Palpable purpura [polyarteritis nodosa (PAN)]
o Erythema nodosum (JIA, SLE, streptococcal, infection, malignancy, IBD, TB)
o Seborrheic dermatitis(histiocytosis)
o Sparse hair (ectodermal dysplasia)

19. Chest & Cardiovascular:
o Murmur (Endocarditis or left atrial myxoma)
o Crackles(lobar pneumonia)
Abdominal:
o Hepato/spleno-megally(salmonella, cat scratch,
endocarditis, malaria),
o point tenderness (Intra-abdominal abscess).
Genito-urinary:
o Girls – Pelvic tenderness (child sex abuse – STI)

20. Musculo-skeletal:
 Tender:
- Bone (osteomyelitis, malignancy)
- Muscle (trichinella,arbovirus,dermatomyositis)
- Trapezius (subdiaphragmatic abscess)
 Reflexes:
- Brisk (hyperthyroid)
- Absent (dysautonomia)

21. Investigation:
 Basic Investigation:
FBC, ESR, CRP, U&E, LFT,
blood culture,
urinalysis, urine & stool culture,
CXR,X-ray sinus cavities

22.  2nd line Non –invasive Investigations:
o Viral cultures,
o Serology for (brucellosis,weil felix for rickettsia,widal
test for salmonella, leptospiral & herpes group viruses)
o ANA,C3,C4 , C-ANCA ,Ig G,A,M,D, &E levels with
subsets,
o TB Quantiferon.
o USS (Abdo,pelvic ,chest & lymph node).
o EBV & CMV titres.
o Ophthalmologist review

23.  Selective Investigations:
o CT or MRI (Abdo & Head) ,
o Bone scan ,
o Tissue, lymph node or bone marrow biopsy.
o ECHO,
o PCR for HIV,
o DNA analysis for fabrys disease .
o PET Scan ,
o White cell scan.

24.  Management:
 Empirical Antibiotics :
Ceftriaxone or cefotaxime if critically ill or fever in
less than 3 months.
 TB treatment after lymph node biopsy, induced
sputum or TB sputum culture.
 Overall it is good practice to avoid antibiotics
until an organism is isolated.

25. Referral
- Gastroenterologist –IBD ,
- Rheumatology –JIA ,CTD
-Oncologist- Leukemia
- Cardiologist-Endocarditis, Left
atrial Myxoma
- ID – TB, Brucellosis, Salmonella,
HIV