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Fever of undetermined origin (FUO), also referred to as pyrexia of unknown origin (PUO), has the following (Petersdorf–Beeson modified) criteria:12
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illness for at least 3 weeks
fevers >38.3°C (100.9°F) on several occasions
undiagnosed after 1 week of intensive study
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Red flag pointers for fever
High fever
Repeated rigors
Drenching night sweats
Severe myalgia (? sepsis)
Severe pain anywhere (? sepsis)
Severe sore throat or dysphagia (? Haemophilus influenzae epiglottitis)
Altered mental state
Incessant vomiting
Unexplained rash
Jaundice
Marked pallor
Tachycardia
Tachypnoea
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Most cases represent unusual manifestations of common diseases and not rare or exotic diseases. Examples are tuberculosis, bacterial endocarditis, hepatobiliary disease and lung cancer.13
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Keep in mind that the longer the duration of fever, the less likely the diagnosis is to be infectious—fevers that last greater than 6 months are rarely infectious (only 6%). One study showed that 9% are factitious.14
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Patients with FUO in definite need of further investigation are:
++
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A diagnostic approach
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A knowledge of the more common causes of FUO is helpful in planning a diagnostic approach (refer to TABLE 53.1).
++
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The history should include consideration of past history, occupation, travel history, sexual history, IV drug use (leads to endocarditis and abscesses), animal contact, medication and other relevant factors. Symptoms such as pruritus, a skin rash and fever patterns may provide clues for the diagnosis. The average patient with a difficult FUO needs to have a careful history taken on at least three separate occasions.15
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A common mistake is the tendency to examine the patient only once and not re-examine. The patient should be examined regularly (as for history taking) as physical signs can develop eventually. HIV infection must be excluded. Special attention should be paid to the following (see FIG. 53.3):
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++
skin—look for rashes, vesicles and nodules
the eyes and ocular fundi
temporal arteries
sinuses and ears (canal and TM)
teeth and oral cavity—? dental abscess, other signs
heart—murmurs, pericardial rubs
lungs—abnormalities including consolidation, pleuritic rub
abdomen—enlarged/tender liver, spleen or kidney
rectal and pelvic examination (note genitalia)
lymph nodes, especially cervical (supraclavicular)
blood vessels, especially of the legs—? thrombosis
urine (analysis)
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Basic investigations include:
++
haemoglobin, red cell indices and blood film
white cell count
ESR/C-reactive protein
chest X-ray and sinus films
urine examination (analysis and culture)
routine blood chemistry
blood cultures
++
Further possible investigations (depending on clinical features):
++
stool microscopy and culture
culture of sputum (if any)
specific tests for malaria, typhoid, EBM, Q fever, brucellosis, psittacosis, cytomegalovirus, toxoplasmosis, syphilis, various tropical diseases and others
NAAT (e.g. PCR) tests
HIV screening
tests for rheumatic fever
tuberculin test
tests for connective tissue disorders (e.g. DNA antibodies, C-reactive protein)
upper GIT series with small bowel follow-through
CT and ultrasound scanning for primary and secondary neoplasia
gall bladder functioning
occult abscesses
MRI—best for detecting lesions of the nervous system
echocardiography—for suspected endocarditis
isotope scanning for specific causes
aspiration or needle biopsy
laparoscopy for suspected pelvic infection
tissue biopsies (e.g. lymph nodes, skin, liver, bone marrow) as indicated
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Fever in children is usually a transient phenomenon and subsides within 4–5 days. At least 70% of all infections are viral. Occasionally a child will present with FUO which may be masked from antibiotic administration. Common causes of prolonged fever in children differ from those in adults. Most cases are not due to unusual or esoteric disorders,17 the majority representing atypical manifestation of common diseases.
++
A summary of the common causes (with the most common ranked first) is as follows.17
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Infectious causes (40%)
++
Viral syndrome
Urinary tract infection
Pneumonia
Pharyngitis
Sinusitis
Meningitis
+++
Collagen–vascular disorders (15%)
++
+++
Neoplastic disorders (7%)
++
Leukaemia
Reticulum cell sarcoma
Lymphoma
+++
Inflammatory diseases of the bowel (4%)
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The diagnosis of septicaemia can be easily missed, especially in small children, the elderly and the immunocompromised, and in the absence of classic signs, which are:
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Patients with septicaemia require urgent referral as it has a very high mortality rate.18 Investigations should include two sets of blood cultures and other appropriate cultures (e.g. urine, wound, sputum). Empirical initial treatment in adults (after blood cultures) is di/flucloxacillin IV and gentamicin IV.19
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Glossary of terms
Bacteraemia The transient presence of bacteria in the blood (usually asymptomatic) caused by local infection or trauma.
Septicaemia (sepsis) The multiplication of bacteria or fungi in the blood, usually causing a systemic inflammatory response (SIRS). SIRS is defined as two or more of (in adults):
Severe sepsis Sepsis associated with organ dysfunction, hypoperfusion or hypotension with two or more of: fever, tachycardia, tachypnoea and elevated WCC.
Septic shock Sepsis with critical tissue perfusion causing acute circulatory failure including hypotension and peripheral shutdown—cool extremities, mottled skin, cyanosis. Consider S. aureus (food poisoning, tampon use) and S. pyogenes.
Pyaemia A serious manifestation of septicaemia whereby organisms and neutrophils undergo embolisation to many sites, causing abscesses, especially in the lungs, liver and brain.
Primary septicaemia Septicaemia where the focus of infection is not apparent, while in secondary septicaemia a primary focus can be identified. Examples of secondary septicaemia in adults are:
urinary tract (e.g. Escherichia coli)
respiratory tract (e.g. Streptococcus pneumoniae)
pelvic organs (e.g. Neisseria gonorrhoeae)
skin (e.g. Staphylococcus aureus)
gall bladder (e.g. E. coli, Streptococcus faecalis)
Patients with septicaemia require urgent referral.