What is the cause of chills in a patient with normal body temperature and normal blood reports?

Chills Without Fever: Diagnostic Approach

Direct Answer

Chills without fever in a patient with normal blood work most commonly indicate an early infectious process where the hypothalamic set-point has been raised but the body has not yet reached the new temperature target, though non-infectious causes including drug reactions, transfusion reactions, and certain malignancies must also be considered. 1

Understanding the Pathophysiology

Chills represent the body's mechanism to generate heat through involuntary muscle contractions when the hypothalamic temperature set-point is elevated above the current core temperature. 1 This explains why patients can experience rigors before measurable fever develops—the body is actively working to reach the new elevated set-point. 1

Immediate Clinical Assessment Priorities

Timing and Pattern Recognition

• Document the exact timing of vital signs relative to chill episodes, as temperature may spike 30-60 minutes after chills begin, and a single normal temperature does not exclude evolving fever. 2
• Obtain serial temperature measurements every 2-4 hours using central methods (bladder catheter, esophageal probe) or oral/rectal routes when central monitoring is unavailable, as peripheral measurements (axillary, tympanic) are unreliable. 2
• Morning versus evening temperature patterns matter: pneumonia typically causes morning peaks, while pyelonephritis and cholangitis produce abrupt evening spikes. 3

High-Risk Infectious Scenarios Requiring Urgent Action

Obtain blood cultures immediately (before any antibiotics) if the patient has: 4, 5, 6

• Any indwelling vascular catheter placed >48 hours ago (obtain one set from catheter hub and one peripheral set simultaneously). 5, 6
• Recent instrumentation (urologic, biliary, or gastrointestinal procedures within 7 days). 3
• Immunocompromised status (chemotherapy, transplant, chronic steroids, HIV). 6
• Prosthetic material (heart valves, vascular grafts, joint prostheses, pacemakers). 6

Critical Infectious Causes to Rule Out

Cholangitis presents with chills occurring with unusually high frequency, often before fever develops, and requires urgent imaging (ultrasound or CT) to assess for biliary obstruction. 3

Inhalational anthrax can present with chills, chest heaviness, and malaise with initially normal chest radiographs—critical to ask about occupational exposure to mail handling or bioterrorism risk. 2

Catheter-related bloodstream infection manifests as chills and rigors even before temperature elevation, particularly with gram-negative organisms. 2

Tickborne rickettsial diseases (RMSF, ehrlichiosis, anaplasmosis) cause chills with fever, but early blood counts may appear normal before characteristic leukopenia and thrombocytopenia develop. 2

Malaria in returned travelers presents with chills preceding fever spikes by 30-60 minutes, and initial blood smears may be negative if obtained between paroxysms. 2

Non-Infectious Causes to Consider

Drug-Related Reactions

• Review all medications started within the past 2 weeks, as drug fever can present with chills before temperature elevation and may occur with antibiotics (especially beta-lactams), anticonvulsants, or allopurinol. 7
• Infusion-related reactions to biologics, chemotherapy, or blood products can cause isolated chills without immediate fever. 2

Transfusion Reactions

• If any blood product was administered within 6 hours, consider febrile non-hemolytic transfusion reaction or acute hemolytic reaction, which both begin with chills. 2

Malignancy-Related

• Lymphoma and leukemia can cause chills as part of B-symptoms even with normal initial blood counts, though this typically occurs with other constitutional symptoms. 2

Diagnostic Algorithm

Step 1: Immediate Actions (Within 30 Minutes)

1. Obtain two sets of blood cultures from separate peripheral sites (20-30 mL per set) using strict aseptic technique before any antibiotics. 4, 5, 6
2. If indwelling catheter present: obtain one set from catheter hub and one peripheral set simultaneously. 5, 6
3. Complete blood count with differential to assess for leukocytosis (≥14,000 cells/mm³), left shift (bands >6% or >1,500/mm³), or cytopenias. 2
4. Comprehensive metabolic panel including liver function tests and creatinine. 2

Step 2: Focused Physical Examination

• Examine all vascular access sites for erythema, induration, purulence, or tenderness within 2 cm of exit site. 2
• Assess for costovertebral angle tenderness (pyelonephritis), right upper quadrant tenderness with Murphy's sign (cholangitis), and new cardiac murmurs (endocarditis). 2, 6
• Inspect skin thoroughly for rash (may be absent in >50% of rickettsial diseases initially), tick attachment sites, or cutaneous anthrax lesions. 2
• Evaluate for meningismus, altered mental status, or focal neurologic deficits. 2

Step 3: Risk-Stratified Imaging

Obtain chest radiograph if: 2

• Respiratory symptoms present (cough, dyspnea, chest discomfort)
• Occupational exposure to mail handling or bioterrorism risk
• Immunocompromised status

Obtain abdominal imaging (ultrasound or CT) if: 2

• Right upper quadrant tenderness or jaundice (cholangitis)
• Recent abdominal instrumentation
• Unexplained abdominal pain with chills

Step 4: Specialized Testing Based on Exposure History

• Recent travel to malaria-endemic areas: thick and thin blood smears (may need repeat every 12-24 hours if initial negative). 2
• Tick exposure or outdoor activities in endemic areas: serologic testing for Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma phagocytophilum (acute and convalescent sera). 2
• Occupational mail handling: consider anthrax testing if mediastinal widening on chest imaging. 2

When to Initiate Empiric Antibiotics

Start empiric broad-spectrum antibiotics immediately (within 1 hour) if: 5

• Hemodynamic instability develops (systolic BP <90 mmHg, MAP <65 mmHg, or lactate >2 mmol/L). 5
• Immunocompromised status with any signs of infection. 6
• Suspected meningitis or encephalitis (altered mental status, meningismus). 2
• Suspected cholangitis (Charcot's triad: fever, jaundice, right upper quadrant pain). 2

Otherwise, await blood culture results if patient is hemodynamically stable, as premature antibiotics significantly reduce culture yield and may obscure the diagnosis. 4, 5

Common Pitfalls to Avoid

• Dismissing chills because temperature is currently normal—chills often precede measurable fever by 30-60 minutes and indicate hypothalamic set-point elevation. 1, 3
• Obtaining blood cultures after starting antibiotics—this reduces yield dramatically and should only occur if antibiotics cannot be delayed beyond 45 minutes in septic patients. 4, 5
• Collecting insufficient blood volume—each blood culture bottle requires 10-30 mL of blood for optimal pathogen detection. 6
• Assuming normal WBC excludes infection—early bacterial infections may present with normal counts before leukocytosis develops, and certain infections (rickettsial diseases) cause leukopenia. 2
• Overlooking medication review—drug fever is a diagnosis of exclusion but must be considered when infectious workup is negative. 7
• Failing to repeat temperature measurements—a single normal reading does not exclude evolving fever; serial measurements over 12-24 hours are essential. 2

Special Consideration: Rising WBC on Antibiotics

If the patient develops rising WBC count while already on antibiotics (even without fever), this suggests inadequate antimicrobial coverage, emerging resistance, or secondary infection, and warrants repeat blood cultures obtained immediately before the next antibiotic dose when drug levels are lowest. 4