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Fever of Unknown Origin - Coggle Diagram
Fever of Unknown Origin
Epidemiology
Prolonged
febrile illness
without
establish aetiology despite extensive evaluation/testing
In returning traveller
History very important in diagnosis
Common diagnoses
Malaria
Dengue fever
Mononucleosis
EBV
CMV
Test with serology
Rickettsial infection
Test with serology
Typhoid/paratyphoid fever
Stool samples
Blood culture
Pathogenesis
Pyrogen
Abnormal elevation of thermoregulatory "set point"
Thermogenesis in fat/muscle
Shivering
Peripheral vasoconstriction
Exogenous
Microbes + products
Endotoxin
Exotoxin
TSST
Enterotoxin
Endogenous
Pyrogenic cytokines
IL-1
IL-6
Tumor necrosis factor (TNF)
Elevated core temperature increases O2 demand
May aggravate pre-existing cardiac/pulmonary condition
In patients with organic brain disease
Elevated temperature can induce mental changes
Infection
Tuberculosis
Most common infectious cause of FUO
Mantoux test/IGRA assays frequently negative in acute infection
Sputum + only in 25%
Pulmonary TB least likely to cause FUO
Occult abscess
Abdominal or pelvic
Sealed perforation
Appendicitis
Diverticulitis
Liver abscess
Biliary/bowel disease
May not show other symptoms
Splenic abscess
Haematogenous seeding
Seen in infective endocarditis
Renal abscess
UTI
Urine cultures may be negative
Osteomyelitis
Vertebral osteomyelitis
Staphylococcal bacteriuria
Mandibular osteomyelities
Dentition
Infective endocarditis
Blood cultures negative in 2-5%
Higher if antimicrobials administered
Culture negative IE
Coxiella burnetii
Brucella
Bartonella
Mycoplasma
Chlamydia
Histoplasma
HACEK group
Non-culture based investigations
Serology
PCR
Echocardiogram positive in > 90% cases
Other endovascular infections (rare)
Mycotic aneurysm
Salmonella
Septic thrombosisphlebitis
Consider prosthetic devices
Malignancy
Non-Hodgkins Lymphoma
Leukaemia
Renal cell carcinoma
Fever in 20% cases
Hepatocellular carcinoma (or other cancers with liver metastases)
Non-infectious inflammatory/connective tissue disease
Adult still's disease
Giant cell arteritis
Systemic lupus erythematosus
Vasculitis
Polymyalgia Rheumatica
Polyarteritis nodosa
Wegener's granulomatosis
Cryolobulinaemia
Drug fever
Drugs stimulate allergic/idiosyncratic reaction or affect thermoregulation
Eosinophilia + rash in 25%
May occur weeks-months after stopping drug
Treatment/Prevention
Whether to treat is debated
May treat in patients with mental impairment and cardiac conditions
Doesn't NEED to be treated
Fever as an indication of sepsis should be treated
Prognosis
Depends on underlying aetiology
Worse if delayed diagnosis
Unresolved cause may have good prognosis
Diagnosis
Classic
Temperature > 38.3ºC
Duration of > 3 weeks
Evaluation of at least 3 outpatient visits OR 3 days in hospital
Nosocomial
Temperature > 38.3ºC
Patient hospitalised ≥ 24 hrs but no fever/incubation on admission
Evaluation of at least 3 days
Immune deficient (neutropenic)
Temperature > 38.3ºC
Neutrophil count ≤ 500 per mm^2
Evaluation of at least 3 days
HIV-associated
Temperature > 38.3ºC
Duration
4 weeks for outpatient
3 days for inpatient
HIV infection confirmed
History + examination
Full review of systems
Travel
Where + when
Animal exposure
Hobbies
Sexual history
Immunosuppression (with degree)
Drugs/toxin history
Localizing symptoms
Fever
Degree
Fever curve
Response to anti-pyretics
Blood
ESR and CRP
Markers of inflammation
LDH
Diagnosis of lymphoma
Autoimmune screen (CT disorders)
Rheumatoid factor
Anti-nuclear antibody (ANA)
Anti-neutrophil cytoplasmic antibody (ANCA)
Creatine phosphokinase (CPK)
Serum protein electrophoresis
Radiology
Chest X-ray
CT thorax, abdomen, pelvic
CT/MRI brain
Isotope bone scane
MRI spine
Fluoro-deoxy-glucose positron emission tomography scan (FDG-PET)
More general, good starting point
Radiolabelled white scane
Microbiology
3 sets of blood cultures
Urine culture and sensitivity (C&S)
CSF
Serum
Histopathology
Biopsy
Liver
Lymph node
Bone marrow
Temporal artery
For giant cell arteritis
Clinical Manifestations
Connective tissue disease
Adult still's disease
Fever
Arthritis
Transient salmon-coloured rash
Giant cell arteritis
Adults > 50 yrs
Fever
Headache
Loss of vision
Symptoms of poly myalgia rheumatic
Raised ESR
Jaw claudication
