Summary![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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” and “Fever of unknown origin.”
Pathophysiology![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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
References:[1]
Emergency evaluation![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Basic approach
- Identify and treat sepsis, if present.
- Identify and treat the underlying cause.
- Provide supportive therapy (antipyretics, IV fluids, tepid sponging).
Red flags
-
General
- Fever lasting > 3 weeks
- Temperature > 40°C (104°F)
- Rash (especially petechial)
- Anemia
- Neutropenia (see “Neutropenic fever”)
- Jaundice
- B symptoms
- Lymphadenopathy (if generalized or persisting > 2 weeks)
-
Localized
- 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
Focused history![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
History of present illness
- Onset
- Duration
- Characteristics (e.g., continuous vs. intermittent or nocturnal, high grade vs. low grade)
Recent exposures
- Travel (see below)
- Sick contacts
- New medication or substance
- Animals, including farm and wild animals
Associated symptoms
- General
- Chills, rigors
- Night sweats
- Unintentional weight loss
-
HEENT
- Nasal congestion and/or rhinorrhea
- Odynophagia
- Dysphagia
- Ear pain and/or discharge
- Pulmonary
- Gastrointestinal
- Abdominal pain
- Nausea and/or vomiting
- Diarrhea
- Constipation or obstipation
- Urogenital
- Neurologic
-
Skin and soft tissue
- Rash
- Localized inflammation
- Pruritus
- Extremities
- Myalgia
- Arthralgia
- Bone pain
- Arthritis
- Joint stiffness or change in range of motion
Past medical history, social history, and family history
- Past medical history
- Past surgical history
- Medications
- Indwelling devices/implants
- Vaccination status (see immunization schedule)
- Menstrual history
- Sexual history
- Allergies
-
Social history
- Occupation
- Pets
- Alcohol
- Drug use
- Tobacco
- Family history
Travel 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
- Accommodation
- 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. [2]
Consider early consultation of an infectious disease specialist for patients with fever who have recently traveled abroad.
Focused examination![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
General
- General appearance
- Age
- Temperature
- Heart rate
- Blood pressure
- Respiratory rate
- Pulse oximetry
HEENT
- Eyes and eyelids
- Fundoscopy
- Ears
- Nose and paranasal sinuses
- Oral cavity, salivary glands, and oropharynx
- Temporal arteries
- Thyroid gland
Cardiovascular
Pulmonary
- Auscultation of the lungs
- Percussion of the lungs
- Evaluation for fremitus and egophony
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
DRE should be avoided in neutropenic patients because of the risk of rectal mucosal injury and bacteremia.
Neurologic
- Orientation to person, place, and time
- Sensitivity to light
- Muscle strength, deep tendon reflexes, and sensory function
- Nuchal rigidity
Lymph nodes
- Palpation of all major lymph node groups
Skin and soft tissue
- Evaluation for pallor and icterus
- Skin appendages
- Skin turgor
- Indwelling devices
- Rash
- Signs of abnormal bleeding
- Ulceration
- Presence of ticks
Extremities
Focused diagnostics![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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.
Laboratory studies
Routine
- CBC with differential
- Blood glucose
- BMP
- LFTs
- Coagulation studies (e.g., INR, PTT)
- Urinalysis with microscopy
In patients with suspected SIRS or sepsis
- Blood gas analysis
- Serum lactate
- Procalcitonin assay
- ESR/CRP
- Blood cultures (at least 2 sets)
- Additional cultures from other sites as indicated
- Chest x-ray
Cultures should be obtained before initiating empiric antibiotic therapy, if possible without delaying the administration of antibiotics.
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 |
|
|
Pulmonary |
| |
Cardiovascular | ||
Abdominal |
|
|
Urologic/pelvic |
|
|
Neurologic/psychiatric |
| |
Skin and soft tissue/bone/lymphatic |
|
|
Rheumatologic |
|
|
Hematologic |
| |
Endocrine |
|
Differential diagnoses by fever characteristics![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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., typhoid fever, lobar pneumonia), Kawasaki disease | |
Remittent fever | Temperature permanently over 38°C (100.4°F); daily fluctuations ≥ 1°C (1.8°F) | Viral infections, acute bacterial endocarditis | |
Intermittent fever [3] | High spike and rapid defervescence | Pyogenic/focal infection, TB, juvenile idiopathic arthritis, infective endocarditis, malaria, leptospira, borrelia, schistosomiasis, lymphoma | |
Recurrent fever [4] | 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 [5] |
Pel-Ebstein fever | Fever lasting 1–2 weeks followed by an afebrile period of 1–2 weeks | Hodgkin lymphoma | |
Periodical fever [6] | Fever that recurs over months or years in the absence of associated viral or bacterial infection or malignancy | Periodic fever syndromes (e.g., familial Mediterranean fever, hyper-IgD syndrome) | |
Others | Still disease, Crohn disease, Behcet disease, relapsing malaria (tertian malaria, quartan malaria), drug fever, factitious fever | ||
Biphasic fever | A fever that breaks and returns once more | Dengue fever , leptospirosis [7] | |
Undulant fever | Temperature rises gradually and falls (like a wave) over days to weeks. | Brucellosis [8][9] | |
Postoperative fever | Has a highly variable course and many different causes; discussed in the article on perioperative management. |
References:[10][11][12][13]
Differential diagnoses by affected system![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
System | ||
---|---|---|
Infectious causes | Noninfectious causes | |
HEENT |
|
|
Pulmonary | ||
Cardiovascular |
| |
Abdominal | ||
Urologic/Pelvic | ||
Neurologic/psychiatric |
| |
Skin and soft tissue/bone/lymphatic | ||
Rheumatologic | ||
Hematologic | ||
Endocrine |
Malignancy involving any system may also cause fever.
Differential diagnoses by associated finding![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
See also “Overview of WBC parameters.”
Associated finding | Differential diagnoses | |
---|---|---|
Jaundice | ||
Rash |
| |
Eosinophilia |
| |
Leukopenia | ||
Anemia |
|
Differential diagnoses by risk factors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Risk factors | Differential diagnoses |
---|---|
Recent international travel | |
HIV infection |
|
Trauma/stress |
|
Drug exposure |
|
Inherited fever syndrome |
|
Autoimmune disease |
Treatment![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
- Antipyretics: indicated in case of intolerable fever; do not prevent febrile seizures
- Antibiotics in case of suspected bacterial infection (e.g., pneumonia)
Acetaminophen is the preferred antipyretic during pregnancy but should be avoided in patients with severe hepatic dysfunction.
NSAIDs are contraindicated in pregnancy and hemorrhagic fevers. They should be used with caution in breastfeeding patients and those with CAD.
Inherited fever syndromes![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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
- Chest pain (40%): due to pleuritis and sometimes pericarditis
- Scrotal pain: due to inflammation of the tunica vaginalis
- Myalgia
- Erysipeloid
- 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
References:[14][15]
Acute management checklist![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
- Treat sepsis (if present).
- Identify and treat the underlying cause.
- Antipyretic therapy
- Evaluate for hypovolemia and consider hydration (see intravenous fluid therapy).
- Tepid sponging
- Consider isolation precautions.