Fever And Hyperthermia: MCCQE1 Preparation Guide

Introduction

Fever (pyrexia) and hyperthermia are common clinical presentations encountered in Internal Medicine and Emergency Medicine. For MCCQE1 preparation, it is crucial to distinguish between these two entities as their pathophysiology, management, and outcomes differ significantly.

Pathophysiology

Understanding the mechanism is key to answering basic science questions on the MCCQE1.

Fever

1. Pyrogens: Exogenous (bacteria, viruses) or Endogenous (IL-1, IL-6, TNF-alpha, Interferons).
2. Mediators: Pyrogens stimulate the release of Prostaglandin E2 (PGE2) in the preoptic area of the hypothalamus.
3. Result: The hypothalamic set-point is raised. The body perceives itself as “cold” and generates heat via shivering and vasoconstriction.

Hyperthermia

1. Mechanism: Failure of thermoregulation.
2. Causes: Exogenous heat exposure (Heat Stroke), drug reactions, or metabolic dysregulation.
3. Result: The body tries to lose heat (vasodilation, sweating) but fails to keep up with heat load. Antipyretics are ineffective here.

Etiology and Differential Diagnosis

Fever of Unknown Origin (FUO)

Classically defined (Petersdorf and Beeson) as:

• Temperature >38.3°C (101°F) on several occasions.
• Duration of fever >3 weeks.
• Failure to reach a diagnosis after 1 week of inpatient investigation (or 3 outpatient visits).

Life-Threatening Hyperthermia Syndromes

These are high-yield topics for the MCCQE1. You must be able to differentiate them based on history and medication lists.

Clinical Assessment

For the MCCQE1 Clinical Decision Making (CDM) component, follow a structured approach.

Management Strategies

Fever Management

The goal is patient comfort and preventing metabolic demand in compromised patients (e.g., cardiac ischemia, traumatic brain injury).

1. Antipyretics:
   • Acetaminophen: 325-1000 mg PO q4-6h (Max 4g/day).
   • Ibuprofen: 200-400 mg PO q4-6h.
   • Note: Avoid Aspirin in children/adolescents due to Reye’s Syndrome.
2. Treat the Underlying Cause: Targeted antibiotics, antivirals, or discontinuation of offending drugs.

Hyperthermia Management

This is a medical emergency.

1. ABCs: Secure airway, breathing, circulation.
2. Rapid Cooling:
   • Evaporative cooling (mist + fans).
   • Immersion (ice water bath) - most effective for exertional heat stroke.
   • Ice packs to axilla/groin (less effective).
3. Specific Antidotes:
   • Dantrolene: For Malignant Hyperthermia and NMS.
   • Cyproheptadine: For Serotonin Syndrome.
   • Benzodiazepines: To control agitation and shivering.

Canadian Guidelines & Public Health

Relevance to the Canadian healthcare system is vital for MCCQE1 success.

1. Lyme Disease

Canadian guidelines suggest prophylaxis with Doxycycline (single dose) if:

• Tick is identified as Ixodes scapularis (blacklegged tick).
• Tick attached for >24 hours (or engorged).
• Exposure occurred in a highly endemic area.
• Prophylaxis can be started within 72 hours of removal.

2. Tuberculosis (TB)

• High incidence in Northern Canadian communities and foreign-born individuals from endemic areas.
• Fever + Night Sweats + Weight Loss + Cough requires isolation and workup for active TB (Sputum AFB x3, CXR).

3. Reportable Diseases

In Canada, certain febrile illnesses must be reported to public health authorities:

• Measles
• Meningococcal disease
• West Nile Virus
• Lyme Disease
• Viral Hemorrhagic Fevers (Ebola, Marburg)

Key Points to Remember for MCCQE1

• Elderly Patients: May not mount a robust fever response even in severe infection (e.g., sepsis). Look for delirium or functional decline.
• Neutropenic Fever: Defined as single oral temp >38.3°C or >38.0°C over 1 hour + ANC <500. This is an oncologic emergency requiring immediate broad-spectrum antibiotics (e.g., Piperacillin-Tazobactam).
• Drug Fever: A diagnosis of exclusion. Usually occurs 7-10 days after starting a drug. Eosinophilia may be present.
• Heat Stroke: Defined by temp >40°C + CNS dysfunction (confusion, coma, seizure). Distinguish from heat exhaustion (normal CNS).

Sample Question

Clinical Scenario

A 24-year-old male is brought to the Emergency Department by his roommate. He was found confused and agitated in his apartment. The roommate reports that the patient has a history of schizophrenia and was recently started on a new high-dose medication regimen. On examination, the patient is stuporous and diaphoretic. Vital signs are: Temperature 40.2°C, HR 120 bpm, BP 160/95 mmHg, RR 24/min, O2 sat 96% on room air. Neurological examination reveals generalized “lead-pipe” rigidity and hyporeflexia.

Which one of the following pharmacologic agents is most appropriate for the specific management of this patient’s condition?

• A. Cyproheptadine
• B. Dantrolene
• C. Lorazepam alone
• D. Acetaminophen
• E. Ceftriaxone and Vancomycin

Explanation

The correct answer is:

• B. Dantrolene

Detailed Analysis

Diagnosis: The clinical presentation is classic for Neuroleptic Malignant Syndrome (NMS).

• Key Features: History of antipsychotic use (schizophrenia treatment), hyperthermia (>40°C), autonomic instability (tachycardia, labile BP), altered mental status, and severe muscle rigidity (“lead-pipe”).
• Pathophysiology: Dopamine D2 receptor blockade in the nigrostriatal pathway and hypothalamus.

Why B is correct: Dantrolene is a direct-acting skeletal muscle relaxant used to treat malignant hyperthermia and NMS. It reduces heat production by inhibiting calcium release from the sarcoplasmic reticulum. Bromocriptine (a dopamine agonist) is also used.

Why other options are incorrect:

• A. Cyproheptadine: This is the treatment for Serotonin Syndrome. While Serotonin Syndrome shares features like fever and altered mental status, it typically presents with hyperreflexia and clonus, not lead-pipe rigidity and hyporeflexia.
• C. Lorazepam: Benzodiazepines are used for agitation in NMS but are supportive. They are not the specific antidote for the underlying rigidity and hyperthermia mechanism, though they are often used adjunctively.
• D. Acetaminophen: This treats fever by resetting the hypothalamic set-point. In NMS, the hyperthermia is due to muscular heat production, not a set-point change. Antipyretics are generally ineffective.
• E. Ceftriaxone and Vancomycin: These are empiric antibiotics for meningitis/sepsis. While infection is a differential, the specific findings of lead-pipe rigidity and recent antipsychotic changes strongly point to NMS.

References

1. Medical Council of Canada. MCCQE Part I Objectives: Fever. Available at mcc.ca.
2. Public Health Agency of Canada. Canadian Guidelines on Lyme Disease.
3. Committee to Advise on Tropical Medicine and Travel (CATMAT). Canadian Recommendations for the Prevention and Treatment of Malaria.
4. Harrison’s Principles of Internal Medicine, 21st Edition. Chapter: Fever and Hyperthermia.
5. Toronto Notes 2024. Infectious Diseases & Internal Medicine Sections.