Fever is defined as an elevation of normal body temperature, which can vary based on a number of factors (e.g., the time of day, geographical location, degree of exertion). In general, fever is defined as a temperature > 38°C (100.4°F). Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever (e.g., URI, gastroenteritis). Laboratory tests and imaging should be guided by the pretest probability of the differential diagnoses. Antipyretics and tepid sponging may be used to decrease body temperature, but treatment of the underlying cause is the main goal when managing febrile patients. See also “Neutropenic fever”.
Inflammation and/or infection → release of endogenous pyrogens (cytokines) induced by exogenous pyrogens (e.g, proteins, lipopolysaccharides) → cytokine-induced upward displacement of the set point of the hypothalamic thermoregulatory center → elevation in body temperature → ↑ immune system activity and ↓ pathogen growth
- Identify and treat sepsis, if present.
- Identify and treat the underlying cause.
- Provide supportive therapy (antipyretics, IV fluids, tepid sponging).
- CNS: neck stiffness, seizures, headache, altered level of consciousness, altered mental status
- ENT: purulent ear discharge, mastoid pain
- Chest: hemoptysis, hypoxemia
- Abdomen: guarding, organomegaly, ascites, melena, hematochezia, persistent vomiting, voluminous diarrhea
- Musculoskeletal: joint swelling, reduced range of motion
- Characteristics (e.g., continuous vs. intermittent or nocturnal, high grade vs. low grade)
- Travel (see below)
- Sick contacts
- New medication or substance
- Animals, including farm and wild animals
Skin and soft tissue
- Localized inflammation
- Past medical history
- Past surgical history
- Indwelling devices/implants
- Vaccination status (see )
- Menstrual history
- Sexual history
- Drug use
- Family history
In addition to the focused history checklist above, the following history should be obtained from a returning traveler:
- Dates of travel
- Mode of travel
- Places visited (incl. travel stops)
- Pretravel vaccination status
- Prophylactic medications
- Activities (e.g., hikes, camping, swimming)
- History of bites and use of repellants
- Exposure to farm animals and livestock
- Ingestion of food or water that is potentially contaminated
- Recent tattoos or piercings
- History of medical care received
In > 25% of returning travelers with fever, a specific cause of the fever cannot be identified. 
Consider early consultation of an infectious disease specialist for patients with fever who have recently traveled abroad.
- Eyes and eyelids
- Nose and paranasal sinuses
- Oral cavity, salivary glands, and oropharynx
- Temporal arteries
- Thyroid gland
Abdominal and pelvic
- Auscultation of the abdomen
- Percussion of the abdomen
- Palpation of the abdomen (including the back)
- Percussion over the costovertebral angles
- Palpation of the spine
- Digital rectal examination
- Pelvic examination
- Orientation to person, place, and time
- Sensitivity to light
- Muscle strength, deep tendon reflexes, and sensory function
- Nuchal rigidity
- Palpation of all major lymph node groups
Skin and soft tissue
- Evaluation for pallor and icterus
- Skin appendages
- Skin turgor
- Indwelling devices
- Signs of abnormal bleeding
- Presence of ticks
The diagnostic evaluation should be guided by the pretest probability of the diagnoses under consideration. The following list includes all of the diagnostic tests that might be of use in diagnosing or ruling out possible etiologies in a patient with fever.
- CBC with differential
- Blood glucose
- Coagulation studies (e.g., INR, PTT)
- Urinalysis with microscopy
- Blood gas analysis
- Serum lactate
- Procalcitonin assay
- Blood cultures (at least 2 sets)
- Additional cultures from other sites as indicated
- Chest x-ray
In admitted patients with a new-onset fever, the minimum initial workup generally should consist of CBC with differential, serum lactate, urinalysis with microscopy, blood cultures (2 sets), and a CXR. Further testing should be guided by the suspected etiology of the fever.
Further diagnostic testing to consider based on suspected localization of symptoms
|Labs||Imaging and other interventions|
|HEENT|| || |
|Skin and soft tissue/bone/lymphatic|
Differential diagnoses by fever characteristics
The pattern of fever may help to determine a diagnosis, although it has limited value in comparison to more specific laboratory tests.
|Differential diagnosis of fever by course|
|Type of fever||Course||Associated diseases|
|Continuous fever||Temperature permanently over 38°C (100.4°F); daily fluctuations < 1°C (1.8°F)||Viral and bacterial infections (e.g., lobar pneumonia),|
|Remittent fever||Temperature permanently over 38°C (100.4°F); daily fluctuations ≥ 1°C (1.8°F)||Viral infections,|
|Intermittent fever ||High spike and rapid defervescence||Pyogenic/focal infection, , , infective endocarditis, malaria, leptospira, borrelia, schistosomiasis, lymphoma|
Recurrent fever 
|Relapsing fever||Days of fever followed by an afebrile |
period of several days and then a relapse into additional days of fever, usually after 14–21 days
|Tick-borne relapsing fever and louse-borne relapsing fever |
|Fever lasting 1–2 weeks followed by an afebrile period of 1–2 weeks|
|Periodical fever ||Fever that recurs over months or years in the absence of associated viral or bacterial infection or malignancy||Periodic fever syndromes (e.g., hyper-IgD syndrome)|
|Others||malaria ( , ), drug fever, factitious fever, , , relapsing|
|Biphasic fever||A fever that breaks and returns once more||, |
|Undulant fever||Temperature rises gradually and falls like a wave over days to weeks.||Brucellosis |
|Has a highly variable course and many different causes; discussed in the article on.|
Differential diagnoses by affected system
|Infectious causes||Noninfectious causes|
|Skin and soft tissue/bone/lymphatic|
Malignancy involving any system may also cause fever.
Differential diagnoses by associated finding
|Associated finding||Differential diagnoses|
Differential diagnoses by risk factors
|Risk factors||Differential diagnoses|
|Recent international travel|
|Drug exposure|| |
|Inherited fever syndrome|
- Antipyretics: indicated in case of intolerable fever; do not prevent febrile seizures
- Antibiotics in case of suspected bacterial infection (e.g., pneumonia)
- Definition: : temperature elevation > 38.3°C (101°F) lasting ≥ 3 weeks without a definitive diagnosis despite thorough clinical investigation
- Criteria: according to the definition + present at ≥ 3 outpatient visits or ≥ 3 days in hospital
- Causes: infection, autoimmune disease, and malignant neoplasm
- Nosocomial FUO
- HIV-associated FUO
- Classical FUO
- The patient history should be taken and physical examination should be performed several times as the inflammatory process develops.
- The pattern of fever should be documented and analyzed.
- History should include:
- Specific investigations should be guided by physical findings and clinical suspicion.
- If there are no diagnostic clues, the following tests should be performed:
- If there are no findings ; from the tests above, abdominal and chest CT should be performed.
- Patients with a negative workup generally have a favorable prognosis, with resolution of fever over time.
Infections and cancer account for the majority of cases of FUO!
Severe febrile neutropenia is life-threatening because of an impaired neutrophil-mediated inflammatory response to bacterial infections. After drawing blood and urine cultures, immediate empiric antibiotic therapy should be initiated.
Inherited fever syndromes
Familial Mediterranean fever (FMF)
- Description: A hereditary autoinflammatory disorder characterized by recurrent, self-limiting fever attacks, serositis, and often other inflamed tissue. Patients do not experience any symptoms between attacks.
- Epidemiology: mostly limited to individuals of eastern Mediterranean descent ; most common inherited fever syndrome
- Genetics: an autosomal-recessive mutation in the MEFV gene on chromosome 16
Clinical presentation: can vary greatly
- All patients experience fever attacks lasting 1–3 days that recur over weeks to months.
- Most patients (95%) experience abdominal pain and arthralgia (75%).
- Other manifestations
- The disorder often goes undiagnosed in patients with mild to moderate symptoms.
- Patients often have an appendectomy scar from a past episode of FMF that was mistaken for acute appendicitis.
- Complication: AA amyloidosis
- Therapy: Prevention of acute episodes and progression to AA amyloidosis through inhibition of granulocyte function by colchicine.
Other hereditary fever syndromes
- Hyper-IgD syndrome
- TNFα reception-associated periodic syndrome