Pyrexia of unknown origin
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An intermittent or persistent fever of >38.2 �C lasting for more
than 2 weeks and for which there is no obvious cause.
- Infection accounts for 45-55% (e.g. endocarditis, tuberculosis,
- Malignancy accounts for 12-20% of cases (e.g. lymphomas or
renal cell carcinoma).
- Connective tissue disorders account for 10-15% (e.g. systemic
lupus erythematosus or polyarteritis nodosum).
- Other causes to be considered include hypersensitivity to drugs,
pulmonary emboli, granulomatous diseases (e.g. sarcoidosis),
metabolic conditions (e.g. porphyria) and a factitious cause (i.e.
fever induced deliberately by the patient).
- The longer the history of fever, the more likely it is that it arises
from a non-infectious cause.
- A detailed history of the presenting complaint.
- Occupational and social history is important (e.g. vets and
are at risk of zoonotic infections, such as brucellosis).
- Travel may suggest exposure to unusual tropical infections.
- Sexual history may indicate possible HIV or related risks.
- Drug history must include those prescribed by a doctor or not,
as some drugs and health products can cause fever.
- Patients may overlook vital information at the first interview;
further opportunities for discussion are often necessary.
- The patient must be examined carefully for localized bone or
joint pain, subtle rashes, lymphadenopathy, abdominal masses,
cardiac murmurs and mild meningism.
- The physical examination should be repeated regularly to
detect changes, such as development of a new cardiac murmur or
enlargement of the liver that becomes palpable only at a later
After the initial history and examination is taken the investigative
process can be divided into three phases.
- Screening investigations, which are performed on all patients
- Investigations that depend on the results of history and physical
- Further screening tests and special imaging techniques: ultrasound,
CT, MRI, echocardiography and dental X-ray.
The results of the preliminary history and examination are taken
together with the results of the primary investigations to plan the
tests that will be performed in the second round. These investigations
are chosen based on syndrome groups (e.g. fever, eosinophilia
and tropical travel). If a diagnosis is not made, further imaging
techniques may be required.
A diagnosis should be made before any antimicrobial therapy is
commenced. In some infections, notably tuberculosis, which may
be suspected but not proven, a trial of therapy may be considered.
If this produces clinical improvement, a full course of chemotherapy
may be initiated.
- Skin sepsis:Streptococcus pyogenes or Staphylococcus aureus
bacteraemia may complicate skin infections.
- Normal flora: The organisms in the normal flora may become
invasive (e.g. dental abscess, cholecystitis, appendicitis or
- Following surgery: A wide range of organisms may be involved.
This problem is particularly important in surgery that involves
prosthetic devices (orthopaedic, cardiovascular, neurosurgical).
- Urinary tract: Enterobacteriaciae or enterococci (see Urinary and genital infections
- Pneumonia: Streptococcus pneumoniae (see Respiratory tract infections
- Meningitis: Neisseria meningitidis or S. pneumoniae.
Diagnosis and Treatment
- Patients are usually severely ill with fever, shock and, sometimes,
- If fever is absent, more common in children and elderly people,
or shock has not yet developed, patients may present with confusion,
drowsiness or being generally unwell.
- It is impossible to distinguish Gram-positive from Gramnegative
- Some infections have characteristic signs (e.g. the purpura of N.
With the exception of suspected N. meningitidis infection, at least
two specimens of peripheral blood should be taken for culture
before therapy is commenced. Other investigations are directed
towards finding the source of the sepsis, such as culture of urine,
sputum, skin swabs and/or CSF. Chest and abdominal X-rays and
abdominal ultrasound should be performed.
Parenteral empirical antibiotics should be chosen based on the
source of infection and the likely infecting organism.
This severe, usually bacteraemic, infection is caused by entry of
pathogens through the placental bed or the cervix within 7 days
of delivery. The organisms involved are either primary Pathogens
introduced by medical manipulation (e.g. S. pyogenes
) or elements
of the normal flora (e.g. Bacteroides
and coliforms) associated with
retained products. Fever, back pain, offensive lochia or shock may
be present and the infection may be complicated by disseminated
intravascular coagulation (DIC). Fever in the early puerperium
should be investigated with blood and urine cultures and endocervical
swabs. Empirical treatment with parenteral antibiotics,
such as a third-generation cephalosporin and metronidazole or a
combination for example of piperacillin plus tazobactam, should
begin without delay. Retained products of conception should be
removed. Intensive care support may be required.