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1 FEVER
2 DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and mitigate potential bias N/A
3 LEARNING OBJECTIVE This lecture is designed to meet the following end-of-week learning objective: 1. Define fever and describe the impact of aging on thermoregulation and develop an approach to fever of unknown origin
4 MODULE OBJECTIVE At the end of this lecture, students should be able to: 1. Explain how body temperature is regulated and how fever occurs 2. Define normal body temperature and fever 3. Develop a differential diagnosis for fever and an approach to fever of unknown origin (FUO)
5 THERMOREGULATION Heat from normal body metabolism, exercise, or the environment Cutaneous blood flow Sweating GI blood flow Hypothalamus Acceptable temperature range (setpoint range) Cooling from the environment Shivering Cutaneous blood flow Mackowiak PA. Chapter 50: Temperature Regulation and the Pathogenesis of Fever. Principles and Practice of Infectious Diseases. 7 th ed Graphic copyright Dr. A. Page.
6 FEVER = in Hypothalamic Setpoint Exogenous Pyrogens (bacteria or bacterial products) Activated Leukocytes Pyrogenic cytokines (IL-1, TNF, IFN, IL-6) PGE2 Circumventricular vascular endothelium Hypothalamic setpoint range Fever Processes usually seen when the body is cold: 1. Cutaneous blood flow = Perception of chills 2. Shivering to generate heat to match rapid rise in setpoint 3. Thermogenesis from brown fat Mackowiak PA. Chapter 50: Temperature Regulation and the Pathogenesis of Fever. Principles and Practice of Infectious Diseases. 7 th ed Graphic copyright Dr. A. Page, adapted from above.
7 NORMAL BODY TEMPERATURE Mackowiak PA, et al. JAMA. Sep 23-30;268(12):
8 Normal Body Temperature depends on Time of Day Mackowiak PA, et al. JAMA. Sep 23-30;268(12):
9 Normal Body Temperature also depends on how you measure it Sund-Levander M, et al. Scand J Caring Sci. Jun;16(2):
10 DEFINITION OF FEVER Classic definition: 38 o C Some authors have suggested: AM temperature 37.2 o C AM or PM temperature 37.8 o C Practically speaking: Monitor closely o C Most would consider 38 o C abnormal Mackowiak PA, et al. JAMA. Sep 23-30;268(12): Mackowiak PA. Chapter 50: Temperature Regulation and the Pathogenesis of Fever. Principles and Practice of Infectious Diseases. 7th ed
11 SPECIFIC DEFINITIONS OF FEVER Febrile Neutropenia Fever Temperature 38.3 o C x1 orally Temperature 38.0 o C for 1 hour Neutropenia ANC < 500 cells/mm 3 ANC < 1000 cells/mm 3 with a predicted decrease to < 500 cells/mm 3 Hughes WT et al. Clin Infect Dis. Mar 15;34(6):
12 FEVER OF UNKNOWN ORIGIN (FUO) Fever 38.3 o C on multiple readings over 3 weeks Original definition: No cause after 1 week of in-patient investigations Revised definition No cause after initial, standard investigations Not applicable to: Immunocompromised patients Nosocomial acquisition (Returned travelers) Children Petersdorf RG, Beeson PB. Med (Baltimore). Feb;40: Petersdorf RG. Arch Intern Med. Jan;152(1):
13 DIFFERENTIAL DIAGNOSIS OF FEVER Infections Non-infectious inflammatory disorders: Autoimmune connective tissue diseases Auto-inflammatory/periodic fever syndromes Malignancy (hematologic or solid tumour) Vascular thrombosis Endocrine/metabolic disorders Drugs/medications Other Hersch EC, Oh RC. Am Fam Physician Jul 15;90(2):91-96.
14 Standard Initial Work-up for Fever without an obvious cause Mourad O, et al. Arch Intern Med. Mar 10;163(5):
15 Selected Causes of Fever of Unknown Origin Roth AR, et al. Am Family Phys. Dec 1;68(11):
16 TAKE HOME MESSAGES 1. Fever is generally defined as an oral temperature 38 o C 2. It occurs if the hypothalamic thermostat is temporarily re-set at a higher level 3. Fever is the final common pathway of inflammation, whether infectious or noninfectious in origin, and therefore has a broad differential diagnosis
17 REVIEW By now you should be able to: 1. Explain how body temperature is regulated and how fever occurs 2. Define normal body temperature and fever 3. Develop a differential diagnosis for fever and an approach to fever of unknown origin (FUO)
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