Fever is one of the most common presenting complaints in clinical practice and emergency settings. From a simple viral illness to life-threatening sepsis, fever can represent a wide spectrum of disease severity. For students and early learners, understanding fever is not about memorizing temperature cutoffs alone—it is about recognizing patterns, identifying red flags, and making timely clinical decisions.
Fever is not a disease by itself. It is a physiological response that often signals an underlying inflammatory, infectious, or systemic process. The real challenge lies in answering one key question: Is this fever benign, or is it dangerous?
Definition of Fever
Fever is defined as a regulated elevation of body temperature due to a reset of the hypothalamic thermoregulatory set point, usually in response to pyrogens.
Commonly accepted thresholds include:
- Oral temperature ≥ 38°C (100.4°F)
- Rectal temperature ≥ 38.3°C (101°F)
It is important to remember that fever is different from hyperthermia, a distinction that has major implications for management.
Normal Body Temperature and Regulation
Normal body temperature is regulated by the hypothalamus, which maintains balance between heat production and heat loss. Heat is generated through metabolism and muscle activity, while heat loss occurs via sweating, radiation, and convection.
The normal diurnal variation means that:
- Body temperature is lowest in the early morning
- Highest in the late afternoon or evening
This explains why mild evening fevers can sometimes be physiological rather than pathological.
Pathophysiology of Fever
Fever occurs when exogenous pyrogens (such as bacterial toxins) stimulate immune cells to release endogenous pyrogens, including:
- Interleukin-1 (IL-1)
- Interleukin-6 (IL-6)
- Tumor necrosis factor-α (TNF-α)
These cytokines increase prostaglandin E2 (PGE2) production in the hypothalamus, raising the temperature set point. As a result, the body perceives itself as “cold,” triggering:
- Shivering
- Peripheral vasoconstriction
- Behavioral responses like seeking warmth
Once the new set point is achieved, the patient feels warm and flushed.
Fever vs Hyperthermia: A Critical Distinction
Although both present with elevated body temperature, fever and hyperthermia are fundamentally different processes.
In fever, the hypothalamic set point is intentionally raised, and antipyretics like paracetamol are effective.
In hyperthermia, the set point is normal, but heat production or exposure overwhelms the body’s ability to dissipate heat. Examples include heat stroke, malignant hyperthermia, and drug-induced syndromes. Antipyretics are ineffective here, and immediate cooling is lifesaving.
This distinction is especially important when temperatures exceed 41°C (105.8°F).
Clinical Classification of Fever
Fever can be classified in multiple ways to guide diagnosis.
Based on duration:
- Acute fever: < 7 days
- Subacute fever: 7–14 days
- Chronic fever: > 14 days
Based on pattern:
- Continuous fever (e.g., typhoid)
- Intermittent fever (e.g., malaria)
- Remittent fever (e.g., infective endocarditis)
Pattern recognition can provide useful diagnostic clues but should never replace systematic evaluation.
Causes of Fever: Broad Differential Diagnosis
Infectious Causes
Infections are the most common cause of fever and include:
- Respiratory infections such as pneumonia and viral URIs
- Urinary tract infections and pyelonephritis
- Gastrointestinal infections
- CNS infections like meningitis and encephalitis
- Skin and soft tissue infections
Non-Infectious Causes
Fever may also arise from:
- Autoimmune and inflammatory disorders
- Malignancies such as lymphoma
- Drug reactions
- Pulmonary embolism
- Endocrine emergencies like thyroid storm
Recognizing non-infectious fever is especially important when cultures are negative and antibiotics fail to improve symptoms.
Red Flags in a Febrile Patient
Certain features should immediately raise concern for serious illness.
These include:
- Hypotension or shock
- Altered mental status
- Immunocompromised state (HIV, chemotherapy, transplant)
- Temperature > 41°C
- Signs of sepsis or organ dysfunction
Such patients require urgent evaluation and often early escalation of care.
Approach to a Patient with Fever
History Taking
A structured history is crucial. Key areas include:
- Duration and pattern of fever
- Associated symptoms like cough, dysuria, headache, or abdominal pain
- Recent travel or environmental exposure
- Drug history
- Immunization status
- Comorbid conditions
Physical Examination
Examination should be head-to-toe and focused on identifying the source of infection or inflammation. Important areas include:
- Skin for rashes or abscesses
- Neck stiffness and neurological status
- Lungs for crepitations
- Abdomen for tenderness or organomegaly
- Joints for signs of septic arthritis
Diagnostic Workup of Fever
The workup should be targeted, not routine.
Common investigations include:
- Complete blood count and inflammatory markers
- Urinalysis and urine culture
- Chest X-ray
- Blood cultures in suspected sepsis
- Lumbar puncture in suspected meningitis
- CT imaging when source is unclear
Unnecessary investigations can delay treatment and increase costs.
Fever and Sepsis: Screening and Early Management
Fever may be the first sign of sepsis. Screening tools like SIRS and qSOFA help identify high-risk patients.
Key components of early sepsis management include:
- Measuring serum lactate
- Early broad-spectrum antibiotics
- Aggressive intravenous fluids
- Source control
- Close reassessment and monitoring
Early recognition and intervention dramatically reduce mortality.
Special Situations
Neutropenic Fever
Defined as fever in a patient with an absolute neutrophil count < 500/µL. It is a medical emergency requiring:
- Immediate broad-spectrum antibiotics
- Protective isolation
- Avoidance of rectal exams or rectal temperature measurement
Fever in Immunocompromised Patients
The differential diagnosis is broader, and infections may present atypically. A low threshold for admission and empiric therapy is essential.
Management of Fever
Treatment should always target the underlying cause.
Symptomatic management includes:
- Antipyretics like paracetamol
- Adequate hydration
- Physical cooling measures if required
Antibiotics should never be prescribed blindly without clinical indication.
Common Pitfalls in Fever Management
Some frequent mistakes include:
- Overuse of antibiotics in viral fever
- Ignoring low-grade fever in high-risk patients
- Relying solely on temperature rather than overall clinical status
- Missing non-infectious causes of fever
Clinical judgment is more important than numbers alone.
Key Learning Pearls
Fever is a sign, not a diagnosis. Always search for the source. High fever with hypotension or altered sensorium should raise immediate concern for sepsis or hyperthermia. Antipyretics treat symptoms, not the cause. In immunocompromised and neutropenic patients, fever is an emergency until proven otherwise.
FAQs
Is fever always harmful?
No. Fever is often a protective immune response and may help fight infection.
When should fever be treated aggressively?
In cases of very high temperature, patient discomfort, cardiovascular compromise, or high-risk patients.
Can fever occur without infection?
Yes. Autoimmune diseases, malignancies, drugs, and endocrine disorders can cause fever.
What is the most dangerous complication of fever?
Progression to sepsis or unrecognized hyperthermia can be life-threatening.
Are antipyretics mandatory in all febrile patients?
No. They are mainly used for comfort unless specific indications exist.
