Fever

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.”

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

• 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

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
  • Cough
  • Dyspnea
  • Chest pain
• Gastrointestinal
  • Abdominal pain
  • Nausea and/or vomiting
  • Diarrhea
  • Constipation or obstipation
• Urogenital
  • Dysuria
  • Hematuria
  • Deep pelvic pain
  • Testicular or scrotal pain
  • Genital ulcers or vesicles
  • Vaginal or urethral discharge
• Neurologic
  • Dizziness
  • Headache
  • Neck stiffness
  • Altered mental status
  • Photophobia
  • Seizures
  • Focal neurological deficits
• 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.

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

• Auscultation of the heart

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

• Capillary refill time
• Joints
• Edema

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

The pattern of fever may help to determine a diagnosis, although it has limited value in comparison to more specific laboratory tests.

References:^{[10][11][12][13]}

Malignancy involving any system may also cause fever.

See also “Overview of WBC parameters.”

• Antipyretics: indicated in case of intolerable fever; do not prevent febrile seizures
  • Acetaminophen
  • NSAIDs
    • Ibuprofen
    • Aspirin
• 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.

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]

• 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.