Fever and Chills

Introduction

• Fever is a sign of disease and plays an important role in defense against infection.
• Fever usually occurs in response to infection (mainly viral).
• Pathogens trigger hypothalamic receptors, resetting the thermostatic mechanisms to maintain a higher core temperature.
• Fever results from increased heat production (e.g., shivering) or decreased heat loss (e.g., peripheral vasoconstriction).
• Fever activates T-cell production, increases interferon effectiveness, and limits viral replication.

Fever of Undetermined Origin (FUO)

Definition (Petersdorf–Beeson Criteria)

• Illness for at least 3 weeks
• Fevers >38.3°C (100.9°F) on several occasions
• Undiagnosed after 1 week of intensive study

Red Flag Pointers for Fever

• High fever
• Repeated rigors
• Drenching night sweats
• Severe myalgia (possible sepsis)
• Severe pain anywhere (possible sepsis)
• Severe sore throat or dysphagia (possible Haemophilus influenzae epiglottitis)
• Altered mental state
• Incessant vomiting
• Unexplained rash
• Jaundice
• Marked pallor
• Tachycardia
• Tachypnoea

Common Causes

• Unusual manifestations of common diseases
  • Tuberculosis
  • Bacterial endocarditis
  • Hepatobiliary disease
  • Lung cancer

Duration of Fever

• Fevers >6 months are rarely infectious (only 6%)
• 9% of prolonged fevers are factitious

Patients Needing Further Investigation

• Babies <3 months of age
• Children with fever >40°C
• Adults >50 years
• People with diabetes
• Immunocompromised individuals
• Travelers

Diagnostic Approach

History

• Past medical history
• Occupation
• Travel history
• Sexual history
• IV drug use
• Animal contact
• Medications
• Symptoms (e.g., pruritus, skin rash, fever patterns)
• Multiple history assessments (at least three occasions)

Examination

• Regular re-examination
• Exclude HIV infection
• Special attention to:
  • Skin (rashes, vesicles, nodules)
  • Eyes and ocular fundi
  • Temporal arteries
  • Sinuses and ears
  • Teeth and oral cavity
  • Heart (murmurs, pericardial rubs)
  • Lungs (abnormalities, pleuritic rub)
  • Abdomen (enlarged/tender liver, spleen, kidney)
  • Rectal and pelvic examination
  • Lymph nodes (especially cervical and supraclavicular)
  • Blood vessels (especially of the legs)
  • Urine analysis

Basic Investigations

• Haemoglobin, red cell indices, blood film
• White cell count
• ESR/C-reactive protein
• Chest X-ray and sinus films
• Urine examination (analysis and culture)
• Routine blood chemistry
• Blood cultures

Further Possible Investigations

• Stool microscopy and culture
• Sputum culture
• Specific tests (malaria, typhoid, EBM, Q fever, brucellosis, psittacosis, cytomegalovirus, toxoplasmosis, syphilis, various tropical diseases)
• NAAT (e.g., PCR) tests
• HIV screening
• Tests for rheumatic fever
• Tuberculin test
• Tests for connective tissue disorders (e.g., DNA antibodies, C-reactive protein)
• Upper GIT series with small bowel follow-through
• CT and ultrasound scanning for primary and secondary neoplasia
• Gall bladder function tests
• Investigations for occult abscesses
• MRI for nervous system lesions
• Echocardiography for suspected endocarditis
• Isotope scanning
• Aspiration or needle biopsy
• Laparoscopy for suspected pelvic infection
• Tissue biopsies (e.g., lymph nodes, skin, liver, bone marrow)

FUO in Children

Common Causes

• Infectious Causes (40%):
  • Viral syndrome
  • Urinary tract infection
  • Pneumonia
  • Pharyngitis
  • Sinusitis
  • Meningitis
• Collagen–Vascular Disorders (15%):
  • Rheumatic arthritis
  • Systemic lupus erythematosus
  • Rheumatic fever
  • Henoch–Schönlein syndrome
• Neoplastic Disorders (7%):
  • Leukaemia
  • Reticulum cell sarcoma
  • Lymphoma
• Inflammatory Diseases of the Bowel (4%)

Septicaemia

definitions:

Bacteraemia The transient presence of bacteria in the blood (usually implies asymptomatic) caused by local infection or trauma.

Septicaemia (sepsis) The multiplication of bacteria or fungi in the blood, usually causing a systemic inflammatory response (SIRS). SIRS is defined as two or more of (in adults):

• temperature >38°C or <36°C
• respiratory rate >20/min
• heart rate >90/min
• WCC >12 × 10⁹/L or <4 × 10⁹/L

Severe sepsis Sepsis associated with organ dysfunction, hypoperfusion or hypotension with two or more of: fever, tachycardia, tachypnoea and elevated WCC.

Septic shock Sepsis with critical tissue perfusion causing acute circulatory failure including hypotension that does not respond to IV fluid administrations and peripheral shutdown—cool extremities, mottled skin, cyanosis. Consider S. aureus (food poisoning, tampon use) and S. pyogenes.

Pyaemia A serious manifestation of septicaemia whereby organisms and neutrophils undergo embolisation to many sites, causing abscesses, especially in the lungs, liver and brain.

Primary septicaemia Septicaemia where the focus of infection is not apparent, while in secondary septicaemia a primary focus can be identified. Examples of secondary septicaemia in adults are:

• urinary tract (e.g. Escherichia coli)
• respiratory tract (e.g. Streptococcus pneumoniae)
• pelvic organs (e.g. Neisseria gonorrhoeae)
• skin (e.g. Staphylococcus aureus)
• gall bladder (e.g. E. coli, Streptococcus faecalis)

Patients with septicaemia require urgent referral.

Signs

• Fever (± shivering)
• Muscle pain
• Rash (suggestive of meningococcus)
• Tachycardia
• Tachypnoea
• Cool extremities

Urgent Referral

• High mortality rate
• Investigations:
  • Two sets of blood cultures
  • Appropriate cultures (urine, wound, sputum)
• Empirical initial treatment in adults:
  • Vancomycin IV
  • Gentamicin IV

Key Facts

• Fever plays a physiological role in defense against infection.
• Normal Body Temperature:
  • Measured orally mid-morning: 36–37.2°C (average 36.8°C).
  • Fever defined as:
    • Early-morning oral temperature >37.2°C.
    • Temperature >37.8°C at other times (typically 4 pm).
  • Oral temperature is about 0.4°C lower than core body temperature.
  • Axillary temperature is 0.5°C lower than oral temperature.
  • Rectal, vaginal, and ear drum temperatures are 0.5°C higher than oral and reflect core body temperature.
• Normal diurnal variation of 0.5–1°C.
• Infections can cause fevers up to 40.5–41.1°C.
• Hyperthermia (temperature above 41.1°C) and hyperpyrexia have no upper limit.
• Infection is the most important cause of acute fever.
• Symptoms associated with fever include sweats, chills, rigors, and headache.
• Non-infectious causes of fever include malignant disease, mechanical trauma, vascular accidents, immunogenic disorders, acute metabolic disorders, and hematopoietic disorders.
• Drugs can cause fever due to hypersensitivity.
  • Important drugs:
    • Allopurinol
    • antihistamines
    • barbiturates
    • cephalosporins
    • cimetidine
    • methyldopa
    • penicillins
    • isoniazid, quinidine
    • phenolphthalein (including laxatives)
    • phenytoin
    • procainamide
    • salicylates
    • sulfonamides.
• Drug fever should abate within 48 hours of discontinuation.
• Fever presentations can vary in the very young, the elderly, immunocompromised, and travelers.

Chills/Rigors

• Abrupt onset of fever with chill or rigor can indicate:
  • Bacteraemia/septicaemia.
  • Pneumococcal pneumonia.
  • Pyogenic infection with bacteraemia.
  • Lymphoma.
  • Pyelonephritis.
  • Visceral abscesses (e.g., perinephric, lung).
  • Malaria.
  • Biliary sepsis (Charcot triad: jaundice, right hypochondrial pain, fever/rigors).
• True chill features:
  • Teeth chattering.
  • Bed shaking.
  • Lasts 10–20 minutes.
  • Shaking cannot be stopped voluntarily.
  • Absence of sweating.
  • Cold extremities and pallor.
  • Dry mouth and pilo-erection.

Hyperthermia

• Definition: Temperature greater than 41.1°C.
• Can result from:
  • Malaria.
  • Heatstroke.
  • CNS tumors, infections, or hemorrhages affecting the hypothalamus.
• Heatstroke:
  • Hot, dry, flushed skin.
  • Rapid pulse.
  • Temperature above 40°C.
  • Confusion or altered consciousness.
  • Immediate cooling required: water application, icepacks, full body immersion (caution in sick people).

Sweats

• Heat loss mechanism; permits rapid heat release by evaporation.
• Sweating usually occurs when temperature falls.
• Characteristic of some fevers (e.g., septic infections, rheumatic fever).

Febrile Neutropenia

• Fever (≥38°C) in a patient with neutrophils <0.5 × 10^9/L.
• Common in cancer therapy patients.
• Requires urgent broad-spectrum antibiotics.

Factitious Fever

• Encountered in hospitalized patients attempting to malinger.
• Suspected when:
  • High temperatures form an atypical pattern.
  • Excessively high temperature (>41.1°C) without corresponding physical signs.
  • No diurnal variation.
• Patient may manipulate the thermometer.

Neuroleptic Malignant Syndrome

• High temperature, muscle rigidity, autonomic dysfunction, altered consciousness.
• Rare, potentially lethal reaction to antipsychotic drugs.

Measurement of Temperature

• Methods:
  • Liquid crystal thermometer.
  • Electronic probe thermometer.
  • Digital infrared aural device.
  • Forehead skin (temporal area) device.
  • Digital peak-hold thermometer (oral and rectal use).
• Oral Use:
  • Place under the tongue at the ‘heat’ pocket.
• Rectal Use:
  • Suitable for babies and young children under 4 years.
  • Insert 2–3 cm past anal verge for 2–3 minutes.
• Axillary Use:
  • Generally unreliable but may be practical for young children.
  • Place high in the axilla for 3 minutes.
• Infrared Aural (Eardrum) Use:
  • Tympanic thermography is accepted standard practice.
  • Temperature measured in 3 seconds.
  • Tympanic membrane reflects core body temperature.
• Digital Electronic Pacifier (Dummy) Thermometer:
  • Popular for infants and younger children.
• Skin Use:
  • Plastic strip thermometers on the forehead are inaccurate.

Clinical Approach

• Evaluate the severity of the problem and nature of the illness.
• Some bacterial infections are life-threatening and require urgent diagnosis and hospital admission.
• Consider fever duration:
  • Less than 3 days: Often self-limiting viral infection.
  • 4–14 days: Suspect less common infection.
  • More than 14 days: Protracted fever (consider FUO).

Fever Patterns

• Intermittent Fever: Temperature rises for a few hours each day, then returns to normal (e.g., pyogenic infections, cytomegalovirus, lymphoma).
• Relapsing Fever: Fever returns to normal for days before rising again (e.g., malaria).
• Remittent Fever: Temperature returns towards normal but remains elevated (e.g., abscesses, carcinoma).
• Undulant Fever: Continuous or remittent fever for several days, followed by afebrile remissions (e.g., brucellosis, Hodgkin lymphoma).
• Continuous Fever: Common with viral infections (e.g., influenza).
• Quotidian Fever: Fever recurs daily (e.g., Pseudomonas infection).

Fever in Children

• Fever of 38.5°C and above is significant.
• Important causes: Urinary infection, meningitis, pneumonia, septicaemia, osteomyelitis, septic arthritis, pertussis, abscess.
• Fever usually responds to viral infection.
• Hyperthermia is uncommon in children.
• Treat febrile convulsions appropriately.

Fever in the Elderly

• Fever is significant and often indicates sepsis.
• Viral infection is less common.
• Elderly are more vulnerable to hyperthermia and hypothermia.

Alarm Bell Signs (Red Flags)

• High fever.
• Repeated rigors.
• Drenching night sweats.
• Severe myalgia.
• Severe pain.
• Severe sore throat or dysphagia.
• Altered mental state.
• Incessant vomiting.
• Unexplained rash.
• Jaundice.
• Marked pallor.
• Tachycardia.
• Tachypnoea.