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Fever

Last updated: September 20, 2021

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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

References:[1]

Basic approach

  • Identify and treat sepsis, if present.
  • Identify and treat the underlying cause.
  • Provide supportive therapy (antipyretics, IV fluids, tepid sponging).

Red flags

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

Past medical history, social history, and 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.

General

HEENT

Cardiovascular

Pulmonary

Abdominal and pelvic

DRE should be avoided in neutropenic patients because of the risk of rectal mucosal injury and bacteremia.

Neurologic

Lymph nodes

Skin and soft tissue

Extremities

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

In patients with suspected SIRS or sepsis

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
  • CT scan of the head, face, and/or neck with IV contrast
Pulmonary
Cardiovascular

Abdominal

Urologic/pelvic

Neurologic/psychiatric
Skin and soft tissue/bone/lymphatic

Rheumatologic

Hematologic
Endocrine

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)
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]

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.

Risk factors Differential diagnoses
Recent international travel
HIV infection

Trauma/stress

Drug exposure
Inherited fever syndrome

Autoimmune disease

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.

  • Definition: : temperature elevation > 38.3°C (101°F) lasting ≥ 3 weeks without a definitive diagnosis despite thorough clinical investigation
  • Classification
  • Diagnostic approach
  • 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.

References:[14][15][16][17]

Familial Mediterranean fever (FMF)

Other hereditary fever syndromes

  • Hyper-IgD syndrome
  • TNFα reception-associated periodic syndrome

References:[18][19]

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