Approach to a patient with PUO



Definition

Fever

  • Persistent / intermittent
  • > 3 weeks
  • >38.3° C on several occasions

Undiagnosed after 1 week of investigations

  • Arbitrary intervals
  • To exclude self-limited viral illnesses (3 weeks)
  • To allow usual investigations to be performed

Aetiology

Most are unusual manifestations of common diseases NOT rare / exotic diseases

Common causes

Causes of PUO %
Infection 40
Malignancy 25
Autoimmune disease 15
Other (drugs, factitious etc) 10
Undiagnosed 10

Aetiology and immunologic status

  • Neutropenia
    • Occult bacterial infections
    • Fungal infections
  • Immunosuppressant drugs/HIV
    • Mycobacteria
    • CMV
    • Fungal infections
    • PCP

If fever > 6 months

  • 20% = infections, cancer or autoimmune

More important causes:

  • Granulomatous diseases (Crohn’s disease, ulcerative colitis, sarcoidosis)
  • actitious fever

Infections

  • Systemic or localized
  • Tuberculosis
  • Occult abscess
  • Endocarditis
  • Osteomyelitis
  • Viral
  • Mycoses
  • Brucellosis

10% POU no Dx found - most resolve spontaneously

Neoplasmia

  • Lymphomas
    • Hodgkin’s
    • NHL
  • Leukemia
  • Hepatocellular Ca
  • 2° in liver
  • Renal cell Ca
  • Atrial myxoma…

Autoimmune

  • Still's disease
  • Giant cell arteritis
  • SLE
  • RA
  • Polymyalgia rheumatica
  • Other vasculitides
    • PAN
    • Wegener's
    • Very high ESR

Drugs

Antimicrobials

Antihistamines

Antiepileptics

  • Barbiturates
  • Phenytoin

NSAIDs

Antihypertensives

  • Hydralazine
  • methyldopa

Miscellaneous

  • Endocrine
    • Hyperthyroidism
    • Adrenal insuffic
    • Phaeocromocytoma
  • Respiratory
    • PE
    • Sarcoidosis
  • Alcoholic hepatitis
  • Factitious fever…

Approach to PUO

4 stages of assessment

Stage 1: Hx & Ex & Preliminary Ix.

Stage 2: Review Hx & Repeat Ex, Specific Ix

Stage 3: Invsaive Ix

Stage 4: Therapeutic trial


Stage 1

History: Nature and Duration of fever. Pattern of fever. Thorough review of systems. Systemic symptoms - weight loss ,anorexia , night sweats. Drug history. Vaccination history. Family history. Infectious contacts. Sexual history. Travel history. Animal exposure. ? immunosuppression ?

Examination: Skin - embolic phenomena, rashes. Eyes - petechiae, Roth spots, jaundice. Lymph nodes – regional/generalised. CVS - new or changing murmur. Chest. Abdomen

Preliminary investigations: WBC and differential count, MSU, Blood cultures x 3, ESR/CRP, CXR, Thick and thin films, Mantoux test

Stage 2 Ix

  • ASO streptococcal disease
  • Hepatitis serology
  • HIV
  • VDRL/TPHA
  • Mantoux
  • Viral screen
    • CMV, EBV
  • Atypical pneumonia
  • Legionnaires
  • Mycoplasma
  • Psittacosis
  • Q fever
  • Brucella
  • Lyme serology
  • LDH
  • Rheumatoid factor
  • Autoantibodies
  • CPK
  • SPEP/UPEP

Stage 3 (invasive Ix)

  • Review the patient's history and examination yet again
  • Ultrasound scan
  • CT TAP/ MRI
  • ECHO
  • Bone marrow aspirate, Tissue / liver / lymph node /temporal art Bx
  • Lumbar puncture
  • Nuclear medicine – bone /WCC scan
  • PET

Stage 4

Clinically challenging - get expert help! Clinical balance between trial antimicrobial (often anti tuberculois regimen) or corticosteroid trial.


Content by Dr Íomhar O' Sullivan. Last review Dr ÍOS 26/05/21.