Fever Of Unknown Origin


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Fever Of Unknown Origin

  1. 1. FEVER OF UNKNOWN ORIGIN Anupama Gowda Medical Student, 3 rd year Medical University of the Americas, Belize campus Internal Medicine Rotation Jackson Park Hospital
  2. 2. THE BASICS OF FEVER <ul><li>PRESENTATION </li></ul><ul><li>Definition </li></ul><ul><li>Differentiation from hyperthermia </li></ul><ul><li>Mechanism </li></ul><ul><li>Measurement </li></ul><ul><li>Classifications </li></ul><ul><li>Importance of fever </li></ul><ul><li>Fever of Unknown Origin (FUO) </li></ul>
  3. 3. DEFINITION <ul><li>Increase in body temperature to levels that are above normal </li></ul><ul><li>Normal = 37.0C or 98.6F </li></ul><ul><li>Temporary elevation in the body’s thermo-regulatory set point (usually 1-2 degrees) </li></ul><ul><li>Most frequent medical symptom </li></ul>
  4. 4. Differentiation from Hyperthermia <ul><li>Increase in body temperature over the body’s thermoregulatory set point </li></ul><ul><li>Due to excessive heat production or insufficient thermoregulatory or both </li></ul>
  5. 5. OUTCOMES from HYPERTHERMIA <ul><li>Previous “normal” body temperature now considered hypothermia </li></ul><ul><li>Effector mechanisms “kick” into action </li></ul><ul><li>Patient will experience the following: cold sensation, increased heart rate and muscle tone, and shivering (an attempt by the body to counteract the perceived hypothermia and in reaching the “new” thermoregulatory set point. </li></ul>
  6. 6. EFFECTOR MECHANISMS <ul><li>Increased heat production causes increased muscle tone, shivering, hormones such as epinephrine and from thyroid to be released </li></ul><ul><li>Prevention of heat loss (e.g. vasoconstriction or crawling under the blanket) </li></ul><ul><li>Brown adipose tissue (mainly in babies) </li></ul><ul><li>Increased blood pressure (from the increased heart rate and vasoconstriction) </li></ul>
  7. 7. MECHANISM <ul><li>Regulated by hypothalamus </li></ul><ul><li>Pyrogens induce fever—two types—endogenous and exogenous </li></ul><ul><li>(1) Exogenous—from outside sources of the body’s system (bacterial substance, LPS) </li></ul><ul><li>(2) Endogenous—from the body (IL-1) </li></ul>
  8. 8. MEASUREMENT <ul><li>Instrument used: thermometer </li></ul><ul><li>Routes to measure: oral, axilla, rectal, and tympanic </li></ul><ul><li>Oral route is the most common route </li></ul><ul><li>Rectal is considered the most accurate and is one degree difference from the oral temperature </li></ul><ul><li>Axilla is 0.5 degrees difference from the oral temperature </li></ul>
  9. 9. Measurement <ul><li>A person has fever if s/he has: </li></ul><ul><li>(1) Rectal >/= 38.0C or 100.4F </li></ul><ul><li>(2) Oral >/= 37.5C or 99.5F </li></ul><ul><li>(3) Axilla >/= 37.2C or 99.0F </li></ul>
  10. 10. Measurement <ul><li>Fluctuations in body temperature can be due to: </li></ul><ul><li>(1) temperature changes throughout day </li></ul><ul><li>lowest at 4:00am, highest at 6:00pm </li></ul><ul><li>(2) individual differences </li></ul><ul><li>(3) women: various points in the menustrual cycles and used in </li></ul><ul><li> fertility planning </li></ul><ul><li>(4) fever can be increased after meals </li></ul><ul><li>(5) Psychological factors </li></ul><ul><li>(6) children have higher temperatures with </li></ul><ul><li> activity </li></ul><ul><li>(7) elderly have a decreased ability to generate body </li></ul><ul><li> heat during fever therefore a low-grade fever can be </li></ul><ul><li> serious </li></ul>
  11. 11. FOUR CLASSIFICATIONS <ul><li>Low-grade: 38.0-39.0C (99.5-102.2F) </li></ul><ul><li>Moderate: 39.0-40.0C (102.2-104.0F) </li></ul><ul><li>High grade: >40.0C (>104.0F) </li></ul><ul><li>Hyperpyrexia: >42.0C (>107.6F) </li></ul>
  12. 12. IS FEVER GOOD OR BAD? Fever is GOOD….. and BAD…
  13. 13. Right Shift : increase in pCO2, temp, 2,3-BPG, altitude, exercise; decrease in pH Left Shift : decrease in pCO2, temp, 2,3-BPG, HbF; increase in pH Hemogloblin-oxygen dissociation curve
  14. 14. Oxygen-Dependent Myeloperoxidase System
  15. 15. SO WHEN IS FEVER “BAD”? <ul><li>>/= 103.0F </li></ul><ul><li>Duration >/= one to three weeks </li></ul><ul><li>If this is only symptom…. </li></ul>
  16. 16. FEVER OF UNKNOWN ORIGIN <ul><li>Two Definitions: </li></ul><ul><li>Persdorf and Beeson (1961): </li></ul><ul><li>(1) Temperature >/= 38.3C (>101.0F) on </li></ul><ul><li>several occasions </li></ul><ul><li>(2) Duration > 3 weeks </li></ul><ul><li>(3) Failure to reach a diagnosis despite </li></ul><ul><li>one week of inpatient investigation </li></ul><ul><li>Duraek and Street modified the definition: </li></ul><ul><li>(1) Dividing into four categories (Classic, Nosocomial, </li></ul><ul><li>Neutropenic, HIV-Associated) </li></ul><ul><li>(2) Differentiating the categories by three features: patient’s </li></ul><ul><li>situation, duration of illness while under investigation, and the </li></ul><ul><li>cause </li></ul>
  17. 17. MAI (Mycobacterium avium/intercellulare), Tuberculosis, Non-Hodgkin’s, drug fever* Perianal infection, aspergillosis, candidemia, drug fever* Septic thrombophlebitis, sinusitis, C-diff, drug fever* Infections, malignancy, inflammatory diseases, drug fever* Causes (few examples) 3 days or 4 weeks as outpatient 3 days 3 days 3 days or 3 outpatient visits Duration of illness while under investigation Confirmed HIV + 1. Neutrophil count less than 500/ul OR 2. Expected to reach that in 1-2 days 1. Hospitalized 2. Acute care 3. No infection when admitted ALL others with fevers greater than/equal to three weeks Patient’s situation HIV-ASSOCIATED NEUTROPENIC NOSOCOMIAL CLASSIC FEATURE
  18. 18. DRUG FEVER <ul><li>Cause common in all categories </li></ul><ul><li>Any febrile pattern which may be elevated by a drug </li></ul><ul><li>Can include any drug BUT pay attention to: anti-microbials (especially Beta lactams), cardiovascular (Quinidine), anti-neoplastic, and those that act on the central nervous system (phenytoin) </li></ul><ul><li>Other symptoms include: </li></ul><ul><li>(1) Bradycardia and hypotension (seen but not </li></ul><ul><li>common </li></ul><ul><li>(2) Eosinophilia and/or rash either: </li></ul><ul><li>--one to three weeks after the start of therapy </li></ul><ul><li>--two to three days after therapy has been stopped </li></ul>
  19. 19. Neutropenic <ul><li>Most susceptible to bacterial and fungal infections (focal), bacteremic infections, infections involving catheters (sepsis and thrombophlebitis), and perianal infections </li></ul><ul><li>Most common: Candida and Aspergillus </li></ul><ul><li>Treatment: </li></ul><ul><li>(1) Vancomycin + Ceftazidime </li></ul><ul><li>(2) Cefepime </li></ul><ul><li>(3) Cabapenem with or without aminoglycoside </li></ul><ul><li>(4) Empirical coverage for bacterial sepsis </li></ul>
  20. 20. HIV-Associated <ul><li>Caused by either HIV by itself or combined with one of the following: </li></ul><ul><li>(1) Mycobacterium avium/intracellulare </li></ul><ul><li>(2) TB </li></ul><ul><li>(3) Pneumocystis </li></ul><ul><li>(4) Salmonellosis </li></ul><ul><li>(5) Cryptococcosis </li></ul><ul><li>(6) Histoplasmosis </li></ul><ul><li>(7) Non-Hodgkin’s Lymphoma </li></ul><ul><li>(8) Drug Fever </li></ul><ul><li>Diagnosis: </li></ul><ul><li>(1) Mycobacterial infections—blood cultures, biopsies from liver, </li></ul><ul><li>bone marrow, and lymph nodes </li></ul><ul><li>(2) CT scan—identify large/mediastinal nodes </li></ul><ul><li>(3) Serological studies—identify the cryptococcal antigen </li></ul><ul><li>(4) Ga-67—pneumocysitis pulmonary infection </li></ul><ul><li>Treatment will be dependent on what is suspected. </li></ul>
  21. 21. NOSOCOMIAL <ul><li>Two “KEY” Points to remember: </li></ul><ul><li>(1) Underlying susceptibility of the patient </li></ul><ul><li>(2) What are the potential complications </li></ul><ul><li>that this patient might concur during the </li></ul><ul><li>hospitalization? (Most Important) </li></ul><ul><li>Then the investigation begins…. </li></ul>
  22. 22. NOSOCOMIAL-INVESTIGATION <ul><li>Physical and/or lab exam: </li></ul><ul><li>(1) Focus—sites where the occult infections might be—original surgical or procedural field, abscesses, hematomas, or infected foreign bodies.. </li></ul><ul><li>(2) Other sites—sinuses of intubated patients, prostatic abscesses in a man with a urinary catheter, suspicion of IV lines, septic phlebitis, and prostheses </li></ul><ul><li>Causes—variety—including: </li></ul><ul><li>(1) Clostridium difficile colitis especially associated with fever and leukocytosis before the onset of diarrhea </li></ul><ul><li>(2) Non-infectious—25% of cases—acalculous cholecystitis, DVT, pulmonary embolism </li></ul><ul><li>(3) Other causes include: drug fever, transfusion rxns, alcohol/drug withdrawal, adrenal insufficiency, thyroiditis, pancreatitis, gout, and pseudogout </li></ul><ul><li>Diagnosis made from: </li></ul><ul><li>(1) physical exams (Be Meticulous!)—repeat if necessary </li></ul><ul><li>(2) “focused” diagnostic techniques </li></ul><ul><li>(3) “speed up” the diagnostic tests </li></ul><ul><li>(4) multiple blood, wound, and fluid cultures </li></ul><ul><li>Treatment should be *SWIFT AND DECISIVE* </li></ul><ul><li>(1) Change IV lines and culture </li></ul><ul><li>(2) Stop the drugs for 72 hours </li></ul><ul><li>(3) Start empirical therapy ONLY IF you suspect bacteremia (e.g. Vancomycin for MRSA, broad- spectrum antibiotics for Gram (-) bacteria—pipercillin/tazobactam, ticarcillin, or clavulanate, imipenem, or meropenem) </li></ul>
  23. 23. CLASSIC <ul><li>Does not “fit” into any of the three categories, then it’s “Classic” </li></ul><ul><li>Includes various causes BUT the leading cause is Infections especially extrapulmonary TB. </li></ul><ul><li>Second most common cause is neoplasms (decrease in malignancies due to the improvement of diagnostic technologies) </li></ul><ul><li>Diagnosis: </li></ul><ul><li>(1) Technologies have made it easy to detect such as CT Scan, MRI, radionuclide scanning, PET scans (increased detections of neoplasms and lymphomas) </li></ul><ul><li>(2) Broad-spectrum antibiotics have decreased the number of infections leading to FUO </li></ul><ul><li>(3) Highly specific and sensitive immunologic testing have decreased the number of undetected SLE and other autoimmune diseases </li></ul><ul><li>(4) There are certain diseases still difficult to diagnose…. WHY? </li></ul>
  24. 24. CLASSIC <ul><li>Delayed antibody responses leading to mononucleosis syndromes (caused by EBV), CMV, or HIV </li></ul><ul><li>Urinary tract infections extending to kidney such as renal malacoplakia with submucosal plaques or nodules </li></ul><ul><li>Diagnoses such as intra-abdominal abscesses that are poorly localized, abscesses involving either the renal, retroperitoneal, and/or para-spinal areas </li></ul>
  25. 25. CLASSIC <ul><li>Top Ten Leading Causes: </li></ul><ul><li>(1) lymphomas </li></ul><ul><li>(2) Collagen Vascular Disease </li></ul><ul><li>(3) Abscesses </li></ul><ul><li>(4) Undiagnosed cause </li></ul><ul><li>(5) Solid tumor </li></ul><ul><li>(6) Thrombosis or hematoma </li></ul><ul><li>(7) Granulomatous disease (non-mycobacterial) </li></ul><ul><li>(8) Endocarditis </li></ul><ul><li>(9) Mycobacterial disease </li></ul><ul><li>(10) Viral disease </li></ul><ul><li>(11) Any other remaining cause </li></ul>
  26. 26. CLASSIC <ul><li>The three most common causes within the elderly include: </li></ul><ul><li>(1) Multisystem disease (most common or frequent—giant cell arteritis) </li></ul><ul><li>(2) TB (most common infection) </li></ul><ul><li>(3) Colon cancer (most important with a malignancy) </li></ul>
  27. 27. CLASSIC <ul><li>Treatment is dependent on the cause </li></ul><ul><li>Harrison’s Principles of Internal Medicine, figure 18-5. </li></ul>
  28. 28. WHAT HAPPENS…? <ul><li>If the duration of fever lasts for more than six months.. Infectious cause decreases, and the cause could be: </li></ul><ul><li>(1) Factitious disease—false deviation of temperature or self-induced disease </li></ul><ul><li>(2) Granulomatous hepatitis </li></ul><ul><li>(3) Neoplasm </li></ul><ul><li>(4) Still’s disease </li></ul><ul><li>(5) Collagen Vascular Disease </li></ul><ul><li>(6) Familiar Mediterranean Fever </li></ul><ul><li>(7) No fever </li></ul><ul><li>(8) Exaggerated circadian temperature rhythm without chills </li></ul><ul><li>(9) Increased pulse </li></ul><ul><li>(10) Nothing identified </li></ul><ul><li>(11) Other abnormalities </li></ul><ul><li>Treatment dependent on the cause. </li></ul>
  29. 29. SUMMARY
  30. 30. THANK YOU