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.