Approach to undifferentiated fever in adults

Essentials

1
Over one-third of patients who have fever for more than 2 to 3 days with no localizing symptoms and signs are likely to have a bacterial infection; half of these will be in the respiratory or urinary tracts.
2
An unexplained fever in a person over the age of 50 should be regarded as due to a bacterial infection until proved otherwise.
3
An undifferentiated fever in an alcoholic patient, an intravenous drug user or an insulin-dependent diabetic is generally an indication for admission to hospital.
4
Any fever in a traveller returned from a malaria-endemic area should be regarded as due to malaria until proved otherwise.
5
Severe muscle pain, even in the absence of overt fever, may be an early symptom of meningococcaemia, staphylococcal or streptococcal bacteraemia.
6
An unexplained rash in a febrile patient should be regarded as meningococcaemia until proved otherwise.
7
The diagnosis of meningococcaemia should be considered in every patient with an undifferentiated fever.
8
There will always be a small number of febrile patients whose sepsis is not initially recognized because they do not appear toxic and their symptoms are non-specific. It is essential that all such patients be encouraged to seek review if they have any clinical deterioration.
9
The omission of fever from the Sepsis 3 definition or Sequential Organ Failure Assessment (SOFA) scoring system should not preclude the clinician from considering sepsis or septic shock when a patient with an undifferentiated fever is being assessed.

Introduction

Fever is a common presenting symptom to the emergency department (ED); about 5% of patients give fever as the reason for their visit. Most patients with fever have symptoms and signs that indicate the site or region of infection. A prospective study of patients aged 16 years or older who presented to an ED with fever ≥37.9°C found that 85% had localizing symptoms and signs that suggested or identified a source of fever and 15% had unexplained fever after the history and examination.

Fever with no localizing symptoms or signs at presentation is often seen in the first day or two of the illness. Patients with such a problem will ultimately prove to have a self-limiting viral infection, but others will have non-viral infections requiring treatment. Among the latter group are illnesses that may be serious and even rapidly fatal.

Over one-third of patients who have fever for more than a few days with no localizing symptoms and signs are likely to have a bacterial infection.

If no cause is found in an adult with fever present for over 3 days, there is a good chance the patient will have a bacterial infection that needs treatment. Over half of these infections are likely to be in the respiratory or urinary tracts.

The most important task in the ED for febrile patients without localizing features is not to miss early bacterial meningitis, bacteraemia (such as meningococcaemia) and early staphylococcal and streptococcal toxic shock syndromes.

Approach

The management of febrile patients varies according to the severity, duration and tempo of the illness, the type of patient and the epidemiological setting. Although steps in the management of a febrile patient in the ED, listed here, may be set out in a sequential manner, in reality the mental processes involved occur simultaneously by the bedside.

Step 1: Identify the very ill.
Step 2: Find localizing symptoms and signs.
Step 3: Look for ‘at-risk’ patients.

Step 1: identify the seriously ill patient who requires urgent intervention

The first step in managing febrile patients is to identify those in need of immediate resuscitation, urgent investigations and empirical therapy. The presence of any of the following features justifies immediate intervention: shock, coma/stupor, cyanosis, profound dyspnoea, continuous seizures and severe dehydration.

Step 2: identify those with localized infections or easily diagnosable diseases

Having excluded those who need urgent intervention, the doctor has more time to attempt a diagnosis. The history and physical examination are usually sufficient to localize the source of community-acquired fever in most cases, especially if the illness has been present for several days.

History

A precise history remains the key to diagnosis of a febrile illness. An inability to give a history and to think clearly is a sign of potential sepsis.

Illness

An abrupt onset of fever, particularly when accompanied by chills or rigors and generalized aches, is highly suggestive of an infective illness.

Localizing symptoms, their evolution and relative severity, help to identify the site of infection; localized pain is particularly valuable in this way.

The severity and course of the illness can be assessed by the patient’s ability to work, to be up and about, to eat and sleep and the amount of analgesics taken.

Previous state of health

Underlying diseases predispose patients to infection at certain sites or those caused by certain specific organisms. Knowledge of any defects in the immune system is similarly helpful. For example, asplenic patients are more prone to overwhelming pneumococcal septicaemia and renal transplant patients to Listeria meningitis.

A past history of infectious diseases, particularly if properly documented, may be useful in excluding infections such as measles and hepatitis. Immunocompromised patients are at significantly higher risk compared with the standard population for contracting an infective illness.

Predisposing events

Recent operations, accidents and injuries and medications taken may be the direct cause of the illness (e.g. drug fever or rash from co-trimoxazole, ampicillin) or may affect the resistance of the patient, predisposing to certain infections. Concurrent menstruation raises the possibility of toxic shock syndrome.

Epidemiology

Information on occupation, exposure to animals, hobbies, risk factors for blood-borne viruses and travel overseas or to rural areas may suggest certain specific infections (e.g. leptospirosis, acute HIV infection, hepatitis C, malaria, etc.).

Contact with similar diseases and known infectious diseases

This information is useful in the diagnosis of problems such as meningococcal infection, viral exanthema, respiratory infection, diarrhoea and zoonoses.

Examination

Physical examination in the febrile patient serves two purposes: to assess the severity of the illness and to find a site of infection.

Bedside assessment of severity and ‘toxicity’ based on intuitive judgement is frequently wrong and many patients with severe bacterial infections do not appear obviously ill or toxic.

Physical examination may yield a diagnosis in a febrile patient who has not complained of any localizing symptoms. The following checklist of special areas to be examined is often useful:

Eyes: Conjunctival haemorrhages are seen in staphylococcal endocarditis and scleral jaundice may be present before cutaneous jaundice is obvious.
Skin: Rashes of any sort, especially petechial rash; cellulitis in the lower legs may present with fever and constitutional symptoms before pain in the leg develops. Evidence of intravenous drug use should be sought at the common injection sites. Be sure to examine the pannus or skin folds in the morbidly obese patients.
Heart: Murmurs and pericardial rubs may be heard.
Lungs: Subtle crackles may be heard in pneumonic patients without respiratory symptoms.
Abdominal organs: Tenderness and enlargement without subjective pain may be the only clue to infections in these organs.
Assess the groin, particularly in a diabetic patient, for signs of necrotizing infection (example: Fournier gangrene).
Lymph nodes: Especially the posterior cervical glands. Tenderness of the jugulo-digastric glands is a good sign of bacterial tonsillitis.
Sore throat may be absent in the first few hours of streptococcal tonsillitis. Examination of the throat may give the diagnosis. Oedema of the uvula is also a useful sign of bacterial infection in that region.
Marked muscle tenderness is a frequent sign of sepsis.
Neck stiffness may be a clue to meningitis in a confused patient who cannot give a history.
Any area that is covered (e.g. under plasters or bandages) must be examined for evidence of sepsis. There are two caveats when local symptoms and signs are being assessed:
Localizing features may not be present or obvious early in the course of a focal infection (e.g. the absence of cough in bacterial pneumonia, sore throat in tonsillitis or diarrhoea in gastrointestinal infections in the first 12 to 36 hours of the illness).
Localizing features may occasionally be misleading. For example, diarrhoea, which suggests infection of the gastrointestinal tract, may be a manifestation of more generalized infection, such as gram negative septicaemia, and crepitations at the lung base may indicate a sub-diaphragmatic condition rather than a chest infection.

Step 3: look for the ‘at-risk’ patient

If no diagnosis is forthcoming after the first two steps, the next task is to identify the ‘at-risk’ patient who may not appear overtly ill but who, nonetheless, requires medical intervention. This applies particularly to those with treatable diseases that can progress rapidly.

Four sets of pointers are helpful in identifying these patients: the type of patient (host characteristics), exposure history, the nature of the non-specific symptoms and how rapidly the illness evolves.

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