Table 6

 Causes of pyrexia of unknown origin

DiagnosisSuggestive features*Useful investigations
*”Suggestive features” may not be present
ACE, angiotensin converting enzyme; ANCA, antineutrophil cytoplasmic antibody; ASOT, anti-streptolysin titre; CT, computed tomography; EBV, Epstein-Barr virus; FBC, full blood count; LDH, lactate dehydrogenase; JIA, juvenile idiopathic arthritis; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; US, ultrasound.
Localised bacterial infections
AbscessLocalising symptomsImaging, white cell scan
EndocarditisNew murmur, haematuriaRepeated blood cultures, echocardiogram
MastoiditisLocalised tendernessCT scan with contrast
OsteomyelitisLocalising symptomsBone scan, MRI
Septic arthritisLocalising symptomsJoint ultrasound, joint aspiration
SinusitisLocal painCT scan with contrast
Other infections
BrucellosisHepatosplenomegaly, farming communityProlonged culture of blood + urine, serology (Brucella spp)
CampylobacterDiarrhoeaStool microscopy and culture
Cat scratch diseaseLymphadenopathy, cat scratchLymph node biopsy, serology (Bartonella)
EBVLymphadenopathyEBV IgM rise, EBV by PCR testing
EnterovirusRashStool viral culture, serology
HepatitisJaundice, tenderness over liverSerology
LeptospirosisFarming, headache, myalgia, then jaundiceSerology (Leptospira interrogans)
Lyme diseaseRash, possibility of tick biteSerology (Borrelia burgdorferi)
MalariaTravel to endemic areaBlood film
SalmonellaDiarrhoeaCulture of stool, urine and blood
ShigellaDiarrhoeaCulture of stool
TuberculosisContact history or residence in an endemic areaTuberculin test, LDH
YersiniaDiarrhoeaCulture stool and blood, serology
Acute rheumatic feverRecent pharyngitis, Ducket Jones criteriaThroat swab, ASOT, Anti-DNAase B, ECG
Post-streptococcal reactive arthritisRecent pharyngitis, arthritisThroat swab, ASOT, Anti-DNAase B
Reiter syndromeUrethritis, arthritis, and conjunctivitisCulture of stool, HLA type (B27 predisposes)
Hodgkin diseaseLymphadenopathy, weight loss, night sweatsLymph node biopsy
LeukaemiaSplenomegaly, anaemia, thrombocytopeniaBlood film, bone marrow examination
LymphomaLymphadenopathyLymph node biopsy, LDH
NeuroblastomaLocal mass, anaemiaUrine catecholamines, US of any mass
Wilms tumourAbdominal pain and mass, haematuriaAbdominal/renal ultrasound
Connective tissue diseases
Beçhet’s diseaseOral and genital ulcers, conjunctivitis
Henoch-Schonlein purpuraTypical rash, haematuria, arthritis
Juvenile dermatomyositisTypical rash, muscle weaknessCreatinine kinase
Polyarteritis nodosaRash, joint involvementBiopsy, renal angiography
SarcoidosisArthritis, uveitisACE, biopsy of affected area if possible
Systemic lupus erythematosusTypical rash, renal involvementAnti ds DNA antibodies, renal biopsy
Systemic onset JIAArthritis, typical rash with fever, miserableFerritin
Wegener’s granulomatosisRespiratory tract involvement, renal failureBiopsy, ANCA autoantibodies
Drug induced feverSuggestive drug historyStop suspected drug
FactitiousNot present in hospitalCareful observation in different settings
Inflammatory bowel diseaseDiarrhoea, weight lossWhite cell scan
Kawasaki diseaseRash, peeling palms, cracked lipsEchocardiogram, US gall bladder
Periodic fever syndromesChronic episodic feverSerial FBC, family history
ThyrotoxicosisWeight loss, tremor, sweating, tachycardiaThyroid function tests, thyroid autoantibodies