Fever 2018-01-30T16:38:19+08:00

Pyrexia of unknown origin is defined as T ≥ 38.3°C on a few occasions for at least three weeks, accompanied by failure to reach a diagnosis after one week of inpatient investigation

Differential diagnosis

  • Infection
    • Respiratory tract
      • Sinusitis
      • Upper respiratory tract infection
      • Community-acquired pneumonia
      • Tuberculosis
      • Pneumocystis jirovecii pneumonia
      • Influenza
    • Cardiac
      • Bacterial endocarditis
      • HACEK organisms are fastidious and may only grow on extended incubation
        • Haemophilus spp.
        • Aggregatibacter spp.
        • Cardiobacterium spp.
        • Eikenella corrodens
        • Kingella spp.
    • Gastrointestinal
      • Whipple’s disease – Tropheryma whippleii causing malabsorption, migratory arthritis
      • Typhoid and other enteric fevers – Salmonella from contaminated food causing abdominal pain, fever, rash “rose spots” with hepatosplenomegaly. Risk of perforation.
      • Viral hepatitis
    • Urinary tract
      • Simple / complicated urinary tract infection
      • Renal abscess
      • Renal carbuncle
    • Soft tissue
      • Septic arthritis
      • Gonococcal arthritis
      • Osteomyelitis
    • Meningoencephalitis
      • Bacterial meningitis
      • Tuberculous meningitis
      • Cryptococcal meningitis
      • Viral encephalitis
    • Systemic infections
      • Q fever – Coxiella burnetti, including Q fever endocarditis; especially in farmers
      • Brucellosis – fever, sweating, migratory myalgia and arthralgia; undercooked meat, unpasteurized milk
      • Leptospirosis – myalgia, cough, diarrhoea, pulmonary haemorrhage; exposure to contaminated water, soil or infected animal tissue
        • Severe disease with jaundice and renal failure – Weil’s disease
      • Cat scratch disease – Bartonella, primary inoculation lesion, generalized lymphadenopathy
      • Rocky Mountain spotted fever – Rickettsia, rash, myalgia, seizures; Americas in the summer
      • Scrub typhus – Orientia, rash, myalgia, intense headache, lymphadenopathy
      • Deep-seated abscess
      • Epstein-Barr virus – lymphadenopathy, fever, rash exacerbated by amoxicillin
      • Cytomegalovirus – diarrhoea, retinitis, pneumonia
      • Human immunodeficiency virus infection
      • Malaria
  • Inflammatory
    • Adult-onset Still’s Disease
      • Fever, often spiking in the evenings
      • Arthralgia and arthritis, often of the wrists, knees and ankles
      • Maculopapular salmon-pink rash over trunk and proximal limbs
      • May have lymphadenopathy, hepatosplenomegaly
      • Yamaguchi or Fautrel’s criteria for diagnosis
    • Systemic lupus erythematosus
    • Rheumatoid arthritis
    • Mixed connective tissue disease
    • Temporal arteritis
    • Sarcoidosis
    • Polymyalgia rheumatica
    • Inflammatory bowel disease
    • Kikuchi disease
    • Systemic vasculitis
  • Neoplastic
    • Renal cell carcinoma
    • Lymphoma
    • Leukaemia
    • Colon cancer
    • Pancreatic cancer
    • Hepatic metastases
    • Hepatoma
  • Drug fever
    • Anti-epileptics
    • Antibiotics, especially beta-lactams, sulphonamides, nitrofurantoin, minocycline
    • Allopurinol
    • Anti-psychotics – neuroleptic malignant syndrome
    • Succinylcholine – Malignant hyperthermia secondary to ryanodine receptor mutation
    • Selective serotonin reuptake inhibitors, monoamine oxidase inhibitors – serotonin syndrome
  • Familial Mediterranean fever
    • Autosomal recessive
    • Attacks of severe pain and fever, lasting 1 – 3 days
    • Pain secondary to serositis – pleuritic, peritonitis, synovitis
    • Entirely well in between attacks
    • Attacks respond very well to colchicine
  • Deep vein thrombosis / pulmonary embolism
  • Hyperthyroidism

History

  • History of presenting complaint
    • Onset of fever
    • Maximal temperature
    • Associated symptoms
      • Altered mentation (if history is from a relative, etc.)
        • Confusion (encephalitis)
        • Neck stiffness (meningitis)
        • Headache (meningitis)
      • Respiratory tract
        • Runny nose, sore throat (URTI, Wegner’s, Churg-Strauss)
        • Facial tenderness (sinusitis)
        • Epistaxis (Wegner’s granulomatosis)
        • Cough – productive / non-productive, haemoptysis (pneumonia)
        • Shortness-of-breath (pneumonia, interstitial lung disease from CTD)
      • Cardiac
        • Janeway lesions / Osler nodes / splinter haemorrhages (infective endocarditis)
        • Chest pain (pericarditis)
        • Symptoms of CCF (acute infective endocarditis)
      • Gastrointestinal
        • Jaundice (hepatitis infection)
        • Diarrhoea (enteric fevers, CMV, HIV, Whipple’s disease)
      • Genitourinary tract
        • Dysuria
        • Renal angle tenderness
        • Genital ulcers (syphilis, Bechet’s)
        • Genital discharge
      • Musculoskeletal
        • Myalgia (non-specific)
        • Arthritis / arthralgia
        • Bone pain (osteomyelitis)
      • Lymphadenopathy (lymphoma, CMV, EBV, HIV, Kikuchi)
      • Inflammatory
        • Rash
        • Mouth ulcers (SLE)
        • Alopecia (SLE)
        • Dry eyes / dry mouth (Sjogren’s)
        • Arthropathy
        • Peripheral neuropathy (vasculitis)
        • Jaw claudication (GCA)
      • Neoplastic
        • Weight loss
        • Change in bowel habit
        • Breast lumps
    • Sick contacts
    • Travel history
    • Animal contact
    • Dietary habits – unpasteurized milk, raw meat
    • Sexual history
  • Past medical history
    • Previous episodes of rheumatic fever
    • Tuberculosis
    • Infective endocarditis
    • Surgery – indwelling prosthetic devices
    • Malignancy
    • Any medical conditions requiring immunosuppression
    • Previous transfusions
  • Drug history
    • Current medications
    • Illicit drug use (endocarditis)
  • Family history – FMF

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