FEVER

Objectives
• Background
• Definition
• Pathophysiology
• Approach
 FEVER in the ER
◼ Fever is part of the presenting complaint in:

◼ 6% of all adult (ages 18-65) visits

◼ 10% to 15% of all elderly (>65 years old) visits

◼ 20% to 40% of all pediatric visits

 Causes
◼ Infection
◼ Other problems:
◼ Autoimmune diseases
◼ Neoplasia

◼ Some medications

◼ Amphetamine abuse

◼ Dehydration

◼ …
 DEFINITION OF FEVER
◼ Fever is an elevation of
body temperature that
exceeds the normal daily
variation, in conjunction
with an increase in
hypothalamic set point
 Pathophysiology
Heat 390C Heat
Production Loss

Heat Production 370C Heat Loss

VARIATION IN TEMPERATURE
◼ Physiologic variation:
◼ Age

◼ Sex

◼ Exercise

◼ Circadianrhythm <1o C
◼ Underlying disorders
 Thermometry
◼ Anatomic variation
◼ Rectal T 0.4oC > Oral T
◼ Oral T 0.5oC > Axillary T
 NORMAL BODY TEMPERATURE

◼ Maximum normal oral

temperature
◼At 6 AM : 37.2
◼At 4 PM : 37.7
Production of endogenous pyrogens
 PHYSIOLOGY OF FEVER
◼ Exogenous pyrogen Activated leukocytes
Endogenous pyrogen(IL1,TNF,…)
Acute Phase Response

◼ Preoptic area of anterior hypothalamus (PGE2)

increase of set point =>
◼ Brain cortex
◼ Vasoconstriction heat conservation
◼ Muscle contraction heat production FEVER
 ACUTE PHASE RESPONSE
◼ Metabolic changes ◼ Altered hepatocyte function
◼ Negative nitrogene (Acute phase reactants)
balance ◼ C reactive protein(increased)
◼ Loss of body weight ◼ Serum amyloid A(increased)
◼ Fibrinogen(increased)
◼ Altered synthesis of ◼ Fibronectin(increased)
hormones ◼ Haptoglobin(increased)
◼ Hematologic alterations ◼ Ceruloplasmin(increased)
◼ Ferritin(increased)
◼ Leukocytosis
◼ Albumin(decreased)
◼ Thrombocytosis ◼ Transferrin(decreased)
◼ Decreased erythrocytosis
 The grade of fever
◼ Low grade fever: 37.3-38 oC
◼ Moderate fever: 38.1-39 oC
◼ High fever: 39.1-41 oC
◼ Hyperpyrexia: >41.5 oC
 Hyperthermia
◼ Hyperthermia is an elevation of body
temperature above the hypothalamic set point
(Heat production exceeds heat loss)
◼ Example: Heat stroke
CAUSES OF HYPERTHERMIA
SYNDROME
◼ Heat stroke: Exercise, Anticholinergic
◼ Drug induced:

Cocaine, Amphetamine, MAO inh

◼ Neuroleptic malignant syndrome:
Phenothiazine
◼ Malignant hyperthermia: Inhalational anesthetics
◼ Endocrinopathy:
Throtoxicosis, pheochromocytoma
 DIAGNOSIS OF
HYPERTHERMIA

◼ History
◼ Antipyretics are not effective

◼ Skin is hot but dry

 Central Fever
(Hypothalamic Fever )
◼ Lesion that has disturbed hypothalamic
temperature-regulation centers
 TREATMENT OF FEVER
◼ Most fevers are associated with

self-limited infections,

most commonly of viral origin

 TREATMENT OF FEVER
◼ Reasons not to treat fever:
◼ The growth and virulence of some organisms
◼ Host defense-related response

◼ Fever is an indicator of disease

◼ Adverse effect of antipyretic drugs

◼ Social benefits
 DISCOMFORT DUE TO
FEVER
◼ For each 1 °C elevation of body temperature:
◼ Metabolic rate increase 10-15%
◼ Insensible water loss increase
300-500ml/m2/day
◼ O2 consumption increase 13%
◼ Heart rate increase 10-15/min
 TREATMENT OF FEVER
◼ Reasons to treat fever:
◼ The elderly individual with pulmonary or cardiovascular
disease
◼ The patient at additional risk from the hypercatabolic state
(Poor nutrition, Dehydration)
◼ The young child with a history of febrile convulsions
◼ Toxic encephalopathy or delirium
◼ Pregnant women (contraversy)
◼ For the patient comfort
◼ Hyperpyrexia
 Treatment Strategies
◼ Acetaminophen
◼ Pediatric dose: 10-15mg/kg q4-6h
◼ Adult dose: 650mg q4-6h
◼ Can be hepatotoxic in high doses
ATTENUETED FEVER RESPONSE
◼ Fever may not be present despite infection in:
◼ Newborn

◼ Elderly

◼ Uremia

◼ Significantmalnourished individual
◼ Taking corticosteroids
APPROACH TO
THE PATIENT
WITH FEVER
 Analysis for fever
◼ Verify presence of fever- True or factitious fever
◼ Duration- Acute or chronic
◼ Mode of onset- Abrupt or gradual
◼ Progression- Continuous or intermittent.
 Approach to the patients with fever
Key factors are:
◼ Age
◼ Height of temperature & Severity of illness
◼ Travel history
◼ Family History
◼ Drug History
◼ Habit History
◼ Underlying illness
◼ Presence of a focus of infection
◼ Laboratory finding
 Age
◼ Elderly and Neonates/ young infants:
◼ May not have the characteristic signs of serious
infection
◼ Localizing features may be absent

◼ Can deteriorate rapidly

 Severity of illness
◼ Toxic patient:
◼ High grade fever
◼ Lethargy

◼ Evidence of poor perfusion

◼ Cyanosis

◼ Hypoventilation or hyperventilation

◼ Tachycardia

◼ The sensitivity of a “toxic appearance” in

detecting serious bacterial infection varied from
11% to 100% in different studies.
 Fever in returning travelers
◼ The number of travelers at risk for febrile illness
is significant.
◼ More than 500 million people cross international
borders each year.
 History
◼ Occupation
◼ Family History
◼ Recent Infection in the Family
◼ Drug History
◼ Antipyretics
◼ Immunosuppressants

◼ Antibiotics
 Habit History

Injection Drug Abuse Excessive Alcohol Use

 Habit History
Consumption of Unpasteurized
Exposure with some animal Dairy Products
 Underlying Diseases
◼ Presence of inserted devices
▪ IV lines, pacemakers, joint prostheses

◼ Immunodeficiency:
◼ Neutropenic cancer patients
◼ transplantation
◼ Corticosteroid intake
◼ Splenectomy
◼ Chronic Diseases:
◼ Cirrhosis
◼ Chronic Heart Diseases
◼ Chronic Lung Diseases
◼ Diabetes
PATTERN OF FEVER
Sustained (Continuous) Fever
Remittent Fever
Intermitent Fever (Hectic Fever)
Relapsing Fever
 Associated Symptoms
◼ Shaking chills
◼ Ear pain, Ear drainage, Hearing loss
◼ Visual and Eye Symptoms
◼ Sore Throat
◼ Chest and Pulmonary Symptoms
◼ Abdominal Symptoms
◼ Back pain, Joint or Skeletal pain
 Physical Examination
◼ Vital signs
◼ Neurological examination
◼ Skin lesions, Mucous membrane
◼ Eyes
◼ ENT
◼ Lymphadenopathy
◼ Lungs & Heart
◼ Abdominal region
◼ Hepatomegaly, Splenomegaly
◼ Abdominal mass
◼ Musculoskeletal
 ACUTE FEBRILE ILLNESS

◼ Most fevers are associated with

self-limited viral infections.

 Initial Laboratory Evaluations in
UNEXPLAINED PROLONGED FEVER
◼ CBC (diff.)
◼ PBS for Malaria and borelia
◼ Two Blood Culture in 30 min. Interval
◼ CXR
◼ U/A
◼ L.F.T. in selected patients
◼ Wright in selected patients
 Red flags

◼ The following are of particular concern:

◼ Persons who are clinically unstable or are at
risk for rapid deterioration
◼ Major alterations of immunity
 FUO
FEVER OF UNKNOWN
ORIGIN
 Classic FUO
◼ Definition:
◼ Fever of 38.3 ˚C or higher on several
occasions
◼ Fever of more than 3 weeks duration
◼ Diagnosis uncertain, despite appropriate
investigations after at least 3 outpatient
visits or at least 3 days in hospital
 Causes of classical FUO

Infections 22-58%

Neoplasms up to 30%

Noninfectiouse up to 25%
inflammatory diseases
Miscellaneous causes up to 25%

Undiagnosed up to 30%
 Infections
commonly associated with FUO
◼ Localized pyogenic infections
◼ Intravascular infections

◼ Systemic bacterial infections (Tuberculosis,

Brucellosis,…)
◼ Fungal infections

◼ Viral infections

◼ Parasitic infections
 Malignancies
commonly associated with FUO
◼ Hodgkin’s disease
◼ Non-hodgkin’s lymphoma
◼ Leukemia
◼ Renal cell carcinoma
◼ Hepatoma
◼ Colon carcinoma
◼ Atrial myxoma
Noninfectious inflammatory diseases
with FUO
◼ Collagen vascular/ ◼ Granulomatouse diseases
hypersensitivity diseases ◼ Crohn’s disease
◼ Lupus
◼ Sarcoidosis
◼ Still’s
disease ◼ Idiopathic
◼ Temporal arteritis granulomatouse
(Giant cell arteritis) disease
 Miscellaneous causes of
FUO
◼ Drug fever
◼ Factitious fever

◼ FMF

◼ Subacute thyroiditis
 Approach to FUO
◼ Determinewhether the patient has
a true FUO
◼ Work up of true FUO:
◼ Careful history
◼ Serial follow-up histories
◼ Careful physical examination
◼ Physical examination should be repeated
 Work up in FUO
◼ Initial noninvasive laboratory examination
◼ Imaging
◼ Invasive Procedures
 Obligatory investigations
◼ CBC and differential, ESR, CRP,
◼ Blood cultures (n = 3),
◼ Urinalysis, urine culture,
◼ Electrolytes, creatinine,
◼ AST, ALT, LDH, Alkaline phosphatase,
◼ Creatine kinase, Total protein, Protein electrophoresis
◼ ANA, Rheumatoid factor
◼ Chest x-ray
◼ Abdominal ultrasonography
◼ Tuberculin skin test or IGRA
 PDC
◼ Potentially diagnostic clues (PDC):
◼ History
◼ Key symptoms

◼ Localizing signs

◼ Initial labrotory tests

◼ If PDCs absent or misleading
◼ Cryoglobulin
and funduscopy
◼ FDG-PET/CT
(or labeled leukocyte scintigraphy or gallium scan)
◼ If Scintigraphy normal
◼ Repeat history and physical examination
◼ Perform PDC-driven invasive testing

◼ If PDCs absent or misleading

◼ Chest CT
◼ Abdominal CT

◼ Temporal artery biopsy (in > 55 years old)

FDG-PET/CT
 LATER-STAGE DIAGNOSTIC TESTS

◼ In some cases, more invasive tests are appropriate.

◼ Abnormalities found with imaging often need to be
confirmed by pathology and/ or culture of biopsy specimens.
◼ If lymphadenopathy is found, lymph node biopsy is
necessary, even when the affected lymph nodes are hard to
reach or when previous biopsies were inconclusive.
◼ In the case of skin lesions, skin biopsy should be
undertaken.
◼ If no diagnosis
◼ In stable condition:

◼ Follow-up for new PDCs

◼ Consider NSAID treatment

◼ Deterioration:

◼ Further diagnostic tests

◼ Consider therapeutic trial