Causes of pyrexia of unknown origin
| Diagnosis | Suggestive 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 | ||
| Abscess | Localising symptoms | Imaging, white cell scan |
| Endocarditis | New murmur, haematuria | Repeated blood cultures, echocardiogram |
| Mastoiditis | Localised tenderness | CT scan with contrast |
| Osteomyelitis | Localising symptoms | Bone scan, MRI |
| Septic arthritis | Localising symptoms | Joint ultrasound, joint aspiration |
| Sinusitis | Local pain | CT scan with contrast |
| Other infections | ||
| Brucellosis | Hepatosplenomegaly, farming community | Prolonged culture of blood + urine, serology (Brucella spp) |
| Campylobacter | Diarrhoea | Stool microscopy and culture |
| Cat scratch disease | Lymphadenopathy, cat scratch | Lymph node biopsy, serology (Bartonella) |
| EBV | Lymphadenopathy | EBV IgM rise, EBV by PCR testing |
| Enterovirus | Rash | Stool viral culture, serology |
| Hepatitis | Jaundice, tenderness over liver | Serology |
| Leptospirosis | Farming, headache, myalgia, then jaundice | Serology (Leptospira interrogans) |
| Lyme disease | Rash, possibility of tick bite | Serology (Borrelia burgdorferi) |
| Malaria | Travel to endemic area | Blood film |
| Salmonella | Diarrhoea | Culture of stool, urine and blood |
| Shigella | Diarrhoea | Culture of stool |
| Tuberculosis | Contact history or residence in an endemic area | Tuberculin test, LDH |
| Yersinia | Diarrhoea | Culture stool and blood, serology |
| Post-infectious | ||
| Acute rheumatic fever | Recent pharyngitis, Ducket Jones criteria | Throat swab, ASOT, Anti-DNAase B, ECG |
| Post-streptococcal reactive arthritis | Recent pharyngitis, arthritis | Throat swab, ASOT, Anti-DNAase B |
| Reiter syndrome | Urethritis, arthritis, and conjunctivitis | Culture of stool, HLA type (B27 predisposes) |
| Malignancy | ||
| Hodgkin disease | Lymphadenopathy, weight loss, night sweats | Lymph node biopsy |
| Leukaemia | Splenomegaly, anaemia, thrombocytopenia | Blood film, bone marrow examination |
| Lymphoma | Lymphadenopathy | Lymph node biopsy, LDH |
| Neuroblastoma | Local mass, anaemia | Urine catecholamines, US of any mass |
| Wilms tumour | Abdominal pain and mass, haematuria | Abdominal/renal ultrasound |
| Connective tissue diseases | ||
| Beçhet’s disease | Oral and genital ulcers, conjunctivitis | |
| Henoch-Schonlein purpura | Typical rash, haematuria, arthritis | |
| Juvenile dermatomyositis | Typical rash, muscle weakness | Creatinine kinase |
| Polyarteritis nodosa | Rash, joint involvement | Biopsy, renal angiography |
| Sarcoidosis | Arthritis, uveitis | ACE, biopsy of affected area if possible |
| Systemic lupus erythematosus | Typical rash, renal involvement | Anti ds DNA antibodies, renal biopsy |
| Systemic onset JIA | Arthritis, typical rash with fever, miserable | Ferritin |
| Wegener’s granulomatosis | Respiratory tract involvement, renal failure | Biopsy, ANCA autoantibodies |
| Miscellaneous | ||
| Drug induced fever | Suggestive drug history | Stop suspected drug |
| Factitious | Not present in hospital | Careful observation in different settings |
| Inflammatory bowel disease | Diarrhoea, weight loss | White cell scan |
| Kawasaki disease | Rash, peeling palms, cracked lips | Echocardiogram, US gall bladder |
| Periodic fever syndromes | Chronic episodic fever | Serial FBC, family history |
| Thyrotoxicosis | Weight loss, tremor, sweating, tachycardia | Thyroid function tests, thyroid autoantibodies |