Fever of Unknown Origin

After a month of junior attending, the blog is back! On Tuesday we discussed an interesting case of fever of unknown origin (FUO). FUO is a clinical entity that is defined as a T > 38.3 on several occasions for >3 weeks, the etiology of which remains unclear after 1 week of diagnosis.

A home-grown review article (see here) highlights the importance of approaching these patients methodically. Of note, this algorithm does not apply to patients who are HIV+ or have a known malignancy, or to children. Up to 20% of patients with FUO remain undiagnosed. Among those in whom a diagnosis is found, 25-30% are found to have infectious causes, 20-30% are found to have inflammatory causes, and 15-20% have malignant causes. The remainder belong to the "other" category - see below.

Infectious Causes of FUO

Bacterial

Endocarditis (apply Duke criteria, think of HACEK organisms and Q fever)

Abscesses (especially intra-abdominal - consider CT)

Dental abscesses, sinusitis

Osteomyelitis

Mycobacteria (TB)

Spirochetes (Syphilis - get VDRL, Lyme disease)

Viral

HIV, HBV, HCV, EBV, CMV

Fungal

Aspergillus, histoplasmosis, coccidiodomycosis, blastomycosis, disseminated candida

Parasites

Malaria, schistosomiasis, Chagas

Inflammatory Causes of FUO

SLE, RA, PMR, Sjogren's

Vasculitis (GCA, WG, PAN)

Behcet's Disease

Sarcoid, IBD, Still's Disease

Malignant Causes of FUO

Leukemia, Lymphoma

Renal Cell CA

Hepatocellular CA

Colorectal CA

Other Causes of FUO

Drug fever

DVT/PE

Subacute thyroiditis

Familial mediterranean fever

Factitious

Disorder of hemostasis

Key principles and approach (see article link above for a great algorithm):

1. Take a thorough Hx and P/E to point you to a focus: thorough ROS, travel/medication/sexual/occupational history, infectious risk factors

2. Stop all non-essential medications and fight the urge to treat empirically

3. Basic investigations: CBC + diff + film, Cr, LFTs, anti-HCV, HBsAg, anti-HBs, Blood cultures x3, UA and urine culture, HIV, CMV/EBV serology may be helpful, ANA, RF, LDH, CXR

4. Abdo CT to rule out abscess and look for tumour, nodes +/- Technitium-based nuclear scan to identify a focus

5. Apply duke criteria and obtain echo, blood cultures

6. Leg dopplers to rule out DVT

7. If older than 50, get temporal artery biopsy to rule out GCA

8. Liver bx can be helpful if LFTs abnormal