What are the possible etiologies of chills in the absence of fever?

Chills Without Fever: Etiologies and Clinical Approach

Chills without documented fever represent a distinct clinical entity that requires systematic evaluation for both physiologic temperature dysregulation and conditions causing subjective chilliness, with critical life-threatening causes including hypothermia, sepsis with inadequate temperature measurement, adrenal insufficiency, and substance withdrawal requiring immediate exclusion.

Critical Life-Threatening Causes to Rule Out First

The most urgent consideration is ensuring accurate temperature measurement, as inadequate technique may miss true fever. Use oral or rectal temperatures rather than unreliable axillary or tympanic measurements 1. Central temperature monitoring (bladder catheter thermistors, esophageal thermistors) provides the most accurate assessment when available 1.

Immediate Life-Threatening Etiologies:

• Hypothermia (core temperature <95°F/35°C) - can present with chills and shivering as compensatory mechanisms 2
• Sepsis with early/masked fever - particularly in elderly, immunocompromised, or those on antipyretics
• Adrenal insufficiency - causes temperature dysregulation and subjective chills 1
• Substance withdrawal (alcohol, opiates, barbiturates, benzodiazepines) - produces chills and autonomic instability 1

Systematic Differential Diagnosis

Neurologic/Endocrine Causes:

• Thyroid storm (paradoxically can present with chills before high fever develops) 1
• Intracranial hemorrhage - disrupts hypothalamic temperature regulation 1
• Stroke affecting thermoregulatory centers 1

Cardiovascular/Hematologic:

• Acute myocardial infarction - can present with chills without fever 1
• Pulmonary embolism/venous thrombosis - causes inflammatory response with chills 1

Medication/Toxin-Related:

• Drug fever (without measured temperature elevation due to measurement timing or antipyretic use) 1
• Neuroleptic malignant syndrome (early presentation) 1
• Serotonin syndrome (early presentation) 1
• Malignant hyperthermia 1

Inflammatory/Autoimmune:

• Cytokine release syndrome - produces subjective chills through cytokine effects 1, 3
• Immune reconstitution inflammatory syndrome 1
• Gout (acute flare) 1

Infection-Related (Without Documented Fever):

• Early infection where cytokine release causes chilliness before temperature elevation 3
• Jarisch-Herxheimer reaction - produces chills as part of inflammatory response 1

Physiologic/Benign Causes:

• Postpartum chills - occurs in 32% of women, potentially related to feto-maternal transfusion reaction 4
• Hormonal fluctuations in young women (premenstrual, related to peripheral circulation changes) 5
• Environmental cold exposure with inadequate thermoregulation 2

Clinical Pitfalls to Avoid

1. Don't assume absence of fever rules out infection - Measure temperature accurately using oral/rectal routes, not axillary or tympanic methods which miss 20-30% of fevers 1

2. Don't overlook medication timing - Antipyretics may mask fever while patient still experiences chills from cytokine effects 3

3. Don't dismiss in postpartum women - This is a common physiologic phenomenon but can also indicate infection 4

4. Don't forget withdrawal syndromes - Particularly dangerous as they can rapidly progress to life-threatening autonomic instability 1

Diagnostic Approach Algorithm

Step 1: Verify accurate temperature measurement (oral/rectal preferred)

Step 2: Assess for immediate threats:

• Vital sign instability suggesting sepsis
• Signs of withdrawal (recent substance use history)
• Neurologic changes (stroke, hemorrhage)
• Cardiac symptoms (MI, PE)

Step 3: Review medication list for causative agents (neuroleptics, serotonergic drugs, anesthetics)

Step 4: Consider inflammatory markers (ESR, CRP) if autoimmune/inflammatory cause suspected

Step 5: In specific populations:

• Postpartum women: likely physiologic 4
• Young women with chronic symptoms: consider hormonal/circulatory factors 5
• ICU patients: broad differential including all causes listed in guidelines 1

The key distinction is that chills represent the body's thermoregulatory response or cytokine-mediated effects 3, which can occur independently of measured fever due to hypothalamic set-point changes, peripheral vasoconstriction, or inflammatory mediators acting directly on tissues rather than through temperature elevation.