Fever
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Fever: Clinical Evaluation & Causes
Definition
Fever is defined as a core body temperature >38.0°C (100.4°F), reflecting an upward resetting of the hypothalamic thermostat. This distinguishes it from hyperthermia (>41.0°C), where the thermostat is not reset but overwhelmed (e.g., heat stroke, drug reactions).
- Normal oral temperature: ~37°C (98.6°F)
- Fever threshold (most guidelines): ≥38.0°C rectally, or ≥37.5°C orally
- Hyperpyrexia: >41.0°C - almost always hyperthermia (not fever), and dangerous to neural tissue requiring rapid cooling (misting + fans, cool water immersion, cooling blankets)
Older adults have a blunted febrile response and lower baseline temperature, so even a lower threshold (~37.8°C/100.4°F) may signal significant illness in frail elderly patients - as noted in Rosen's Emergency Medicine.
Pathophysiology (Brief)
Exogenous pyrogens (bacteria, viruses, toxins, immune complexes) stimulate release of endogenous pyrogens - cytokines such as IL-1, IL-6, TNF-α, and IFN-γ. These act on the hypothalamic thermoregulatory center to produce prostaglandin E2 (PGE2), which raises the set point. NSAIDs/aspirin block PGE2 synthesis and reduce fever.
The sequence:
- Set point rises → patient feels chilled (body is below new set point)
- Shivering generates heat → body temperature rises to meet new set point
- Patient feels hot and sweats when the set point returns to normal
Moderate fever may actually aid host defenses - improving lymphocyte function, enhancing chemotaxis, and inhibiting microbial replication.
Clinical Evaluation
History - Key Elements
| Feature | What to Elicit |
|---|---|
| Fever pattern | Continuous, remittent, intermittent, relapsing |
| Onset & duration | Acute (<1 wk) vs. subacute/chronic (>3 wks = consider FUO) |
| Associated symptoms | Chills/rigors, night sweats, weight loss, rash, cough, dysuria, headache, stiff neck |
| Travel history | Malaria, typhoid, dengue, enteric fever |
| Exposures | Animals (zoonoses), sick contacts, sexual history, IV drug use |
| Medications | Drug fever, immunosuppressants (alter presentation) |
| Vaccination history | Especially in children |
| Ethnicity | Some FUO causes are ethnicity-linked |
| Immunosuppression | Lowers threshold for opportunistic infections |
Physical Examination
Systematic head-to-toe assessment:
- Skin: rashes (petechiae/purpura = meningococcemia; maculopapular = viral, drug, rickettsia; vesicles = varicella, HSV; erythroderma = toxic shock)
- Eyes: conjunctivitis, Roth spots (endocarditis), jaundice (hepatitis, malaria)
- Ears/sinuses/throat: otitis, sinusitis, pharyngitis, strawberry tongue (Kawasaki, scarlet fever)
- Lymph nodes: adenopathy (EBV, lymphoma, TB, HIV)
- Heart: new murmur (infective endocarditis)
- Lungs: consolidation signs (pneumonia)
- Abdomen: organomegaly, tenderness (appendicitis, cholangitis, pyelonephritis)
- Joints: arthritis (reactive, septic, rheumatologic)
- Neurological: meningismus, altered mental status
Differential Diagnosis by Category
1. Infectious (Most Common Overall)
Life-threatening (do not miss):
- Sepsis / septic shock
- Bacterial meningitis
- Meningococcemia
- Necrotizing fasciitis
- Infective endocarditis
- Peritonitis / intra-abdominal sepsis
Common causes by system:
| System | Examples |
|---|---|
| Respiratory | Community-acquired pneumonia (S. pneumoniae, Haemophilus, atypicals), influenza, COVID-19, TB |
| Urinary | UTI, pyelonephritis, urethritis |
| CNS | Viral/bacterial meningitis, encephalitis, brain abscess |
| Skin/soft tissue | Cellulitis, abscess, erysipelas |
| GI | Gastroenteritis (Salmonella, Shigella, Campylobacter), C. difficile colitis, cholangitis |
| Bone/joint | Septic arthritis, osteomyelitis |
| Viral | EBV (most common viral FUO), CMV, HIV, HSV, enterovirus, arboviral (dengue, Zika) |
| Parasitic | Malaria (must consider in any returning traveler!) |
In patients over 65, >80% of bacterial infections originate from respiratory, genitourinary, and skin/soft-tissue systems - per Rosen's Emergency Medicine.
2. Non-Infectious Causes (Box 8.1 in Rosen's)
These are less common but must not be missed:
| Category | Examples |
|---|---|
| Rheumatologic / Inflammatory | SLE, adult-onset Still's disease, vasculitis, rheumatoid arthritis, polymyalgia rheumatica, acute rheumatic fever |
| Neoplastic | Lymphoma (Hodgkin's - classic B symptoms: fever, night sweats, weight loss), leukemia, renal cell carcinoma, hepatocellular carcinoma |
| Drug fever | Beta-lactams, sulfonamides, anticonvulsants, allopurinol, heparin - typically 7-10 days after drug initiation |
| Thromboembolic | DVT, pulmonary embolism (low-grade fever) |
| Endocrine | Thyroid storm, adrenal insufficiency |
| CNS | Hypothalamic dysfunction, subarachnoid hemorrhage |
| Postoperative | Transfusion reaction, wound infection, pneumonia, line sepsis, UTI, atelectasis |
| Tissue injury | MI, infarction, hematoma resorption |
Diagnostic Approach
Step 1: Stability Assessment First
Per Rosen's Emergency Medicine: the primary decision is assessing stability.
- Unstable (altered mental status, respiratory distress, hemodynamic instability): resuscitate immediately - airway, IV access, fluids, empiric broad-spectrum antibiotics - do not wait for culture results
- Stable: systematic workup
Step 2: Laboratory Evaluation
Guided by history and examination:
| Test | When to Order |
|---|---|
| CBC with differential | Most febrile patients |
| CRP / ESR | Inflammatory markers (less specific) |
| Procalcitonin | Bacterial vs. viral infection, sepsis monitoring |
| Blood cultures (x2) | Bacteremia, endocarditis, sepsis |
| Urinalysis + urine culture | All febrile patients without clear source |
| Chest radiograph | Respiratory symptoms or unclear source |
| LFTs | GI symptoms, jaundice, travel history |
| HIV serology | Risk factors, unexplained lymphadenopathy |
| Metabolic panel | Assess organ function, hydration |
| Thick/thin blood smear | Travel to malaria-endemic regions |
Step 3: Imaging
- CXR: pneumonia, mediastinal adenopathy
- CT chest/abdomen/pelvis: occult infection, abscess, malignancy
- Echocardiogram: if endocarditis suspected
- MRI: CNS infection, osteomyelitis
Special Scenario: Fever of Unknown Origin (FUO)
Classic definition (Petersdorf & Beeson, 1961):
- Temperature ≥38.3°C on multiple occasions
- Duration >3 weeks
- No diagnosis after 3 outpatient visits OR 3 days of in-hospital evaluation
Modern threshold has migrated toward 1-2 weeks, per Swanson's Family Medicine Review.
Most common FUO causes by category (adults):
- Infectious (most common) - TB, endocarditis, occult abscess, EBV/CMV
- Rheumatologic / Inflammatory - SLE, adult Still's disease, vasculitis
- Neoplastic - Lymphoma, RCC, hepatocellular carcinoma
- No diagnosis found - ~23% of pediatric cases; higher in some adult series
Initial FUO workup:
- Detailed history and physical exam (most valuable step)
- CBC, metabolic panel, ESR, CRP
- Blood cultures, urine culture
- Chest X-ray
- Consider: ANA, ANCA, RF, SPEP, TSH, ferritin (very high in Still's disease), LDH
- Procalcitonin for bacterial vs. inflammatory distinction
- CT chest/abdomen/pelvis if above unrevealing
- PET scan for occult malignancy or vasculitis in refractory cases
Red Flags Requiring Urgent Evaluation
- Temperature >41°C (hyperthermia - cool immediately)
- Petechial or purpuric rash (meningococcemia)
- Neck stiffness + fever + headache (meningitis)
- Altered mental status
- Hemodynamic instability
- Immunocompromised host (neutropenic fever - treat within 1 hour)
- Returning traveler with fever (rule out malaria urgently)
Sources: Rosen's Emergency Medicine (9th ed.), Goldman-Cecil Medicine, Swanson's Family Medicine Review - all via the Medical Textbook Library.
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