Unknown Fever
Definition
Prolonged fever without a diagnosis despite extensive testing
Categories
Infections = 38%
Connective tissue = 21%
Malignancies = 12%
Misc = 6%
No diagnosis = 23%
Infections
A systemic review of 832 cases worldwide showed
Tuberculosis = 34% (presentations that escape detection as extrapulmonary and miliary)
Brucellosis = 10%
Endocarditis = 8% (cultures negative in up to 5%, TOE is positive in 90% of cases)
Q fever
Whipple’s
Brucella
Mycoplasma
Chlamydia
Histoplasma
Legionella
Bartonella
HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) need 21 days of incubation on blood cultures
Abscess = 7% (commonly abdomen or pelvis, conditions that predispose are cirrhosis, immunosuppression, recent surgery and diabetes)
Other
HIV
Herpesviruses e.g. CMV EBV
Pneumonia
UTI
Typhoid
Osteomyelitis (vertebral, mandible, discitis)
Dental abscesses
Fungal (Sporotrichosis)
Opportunistic with HIV (CMV, MAC, PCJ, Fungi, Protozoa)
Secondary syphilis
Disseminated gonoccocemia, meningococcemia, leishmaniasis, yersiniosis
Tick-borne (Babesiosis, Lyme, Anaplasmosis, Ehrlichiosis, Borrelia)
Pulmonary infections (Q fever, leptospirosis, psittacosis, tularaemia, melioidosis)
Helminths
Connective Tissue
Temporal arteritis
Adult-onset Still’s disease (fever, arthritis, rash)
Polyarteritis nodosa
Takayasu’s arteritis
Granulomatosis with polyangiitis
Mixed cryoglobulinemia
Sarcoidosis
SLE
Rheumatoid arthritis
Malignancy
Lymphoma
Leukemia
Multiple Myeloma
Renal cell carcinoma (20% of cases have fever)
Hepatocellular and mets to liver
Atrial myxomas
Sarcoma
Miscellaneous
Drugs (allergic or idiosyncratic reaction)
Factitious
Disordered heat homeostasis (hypothalamic dysfunction following a stroke or ABI, or skin conditions such as ichthyosis)
Alcoholic hepatitis (fever hepatomegaly, jaundice and anorexia)
Venous thrombosis (dyspnoea, pleuritic pain, cough, haemoptysis)
Haematoma with subsequent inflammation
Hyperthyroidism and thyroiditis
Phaeochromocytoma and adrenal insufficiency
Hereditary period fever syndromes (Mediterranean fever, TRAPS)
Diagnostic approach
Study showed 10 potential diagnostic clues per patient from history and exam
3 potential clues from laboratory testing
81% of these clues were misleading
History
Travel
Animal exposure
Immunosuppression
Drugs and toxin history
Localising symptoms
Blood tests
FBC, Platelets, LFT, UEC
CRP/ESR (ESR>100 = 58% malignancy, 25% infection or systemic)
Blood cultures +/- test for 21 days
Urinalysis
=======
LDH
TB test
HIV
If abnormal LFT then Hepatitises
LDH
Rheumatoid Factor
CK
EBV test
ANA
SPEP
Imaging
Routine CXR (helpful in 8% of cases, false positive in 11% of cases)
CT chest abdo pelvis (CT chest helpful 9%, false positive 8% and CT abdo helpful 12%, false positive in 10%)
PET scan (helpful in 23%, false positive in 10%)
References
UpToDate - Less common causes of FUO [Needs Log In]
UpToDate - Causes of FUO in adults [Needs Log In]
UpToDate - Approach to adults with FUO [Needs Log In]