1 / 73

FUO Basics

FUO Basics. Patty W. Wright, MD & C. Buddy Creech, MD, MPH with appreciation to William Goins, MD and Bryan Youree, MD March 2011. Objectives. To discuss the definition of fever of unknown origin (FUO) the classifications of FUO the most common etiologies of FUO

ezra-merrill
Download Presentation

FUO Basics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. FUO Basics Patty W. Wright, MD & C. Buddy Creech, MD, MPH with appreciation to William Goins, MD and Bryan Youree, MD March 2011

  2. Objectives • To discuss • the definition of fever of unknown origin (FUO) • the classifications of FUO • the most common etiologies of FUO • the diagnostic work-up of patients with FUO

  3. What is a normal body temperature?

  4. Normal Body Temperature (Adults) • 1 million axillary temperatures measured twice daily in 25,000 healthy adults • Mean temperature: 37°C (36.2 – 37.5°C) • Readings >38.0°C were deemed as “suspicious/probably febrile” • Thermometers may have read 1.4 – 2.2°C (2.6 – 4.0°F) higher than today’s instruments Wunderlich C. Das Verhalten der Eigenwärme in Krankenheiten. Leipzig, Germany: Otto Wigard;1868. Mackowiak, et al., JAMA 1992;268:1578

  5. Normal Body Temperature (Adults) Mackowiak, et al., JAMA 1992;268:1578

  6. Normal Body Temperature (Adults) • Mean temperature varied diurnally • Low: 6 AM • Peak: 4 – 6 PM • Mean variability: 0.5°C (0.9°F) • Women had slightly higher temperatures • Black subjects tended to have higher temperatures than whites Mackowiak, et al., JAMA 1992;268:1578

  7. Normal Temperature Curves (Children)

  8. What is hyperthermia?

  9. Hyperthermia • Unregulated elevation of temperature • Does not involve hypothalamic thermoregulatory center • Cytokines not directly involved

  10. Excessive heat production Exertional hyperthermia Thyrotoxicosis Pheochromocytoma Cocaine Delerium tremens Malignant hyperthermia Disorders of heat dissipation Heat stroke Autonomic dysfunction Disorders of hypothalamic function Neuroleptic malignant syndrome CVA Trauma Mechanisms of Hyperthermia

  11. What is fever?

  12. Fever • Resetting of the thermostatic set-point in the anterior hypothalamus • Initiation of heat-conserving mechanisms • Cytokine-mediated

  13. What is a Fever of Unknown Origin?

  14. Fever of Unknown Origin • Temp > 101°F (38.3°C) on several occasions • Fever of at least 3 weeks duration • No diagnosis after a 1 week evaluation in the hospital or (in the modern era) a reasonable outpatient work-up Petersdorf RG, Beeson PB. Medicine 1961;40:1-30.

  15. Historical Causes of FUO • Hippocrates: Excess of yellow bile • Middle Ages: Demonic possession (encephalitis?) • 18th Century: Friction associated with the flow of blood through the vascular system and from fermentation and putrefaction occurring in the blood and intestines

  16. aAll require temperatures of ≥38.3°C (101°F) on several occasions. bIncludes at least 2 days’ incubation of microbiology cultures. Modified from DT Durack, AC Street, in JS Remington, MN Swartz (eds): Current Clinical Topics in Infectious Diseases. Cambridge, MA, Blackwell, 1991.

  17. What are the three most common causes of FUO (in general)?

  18. Classifications of FUO Modified from DT Durack in Mandell, Bennett, and Dolin. Principles and Practice of Infectious Diseases, 2005. 6th ed.

  19. Evolving Etiology of FUO in Adults Mourad, et al. Arch Intern Med. 2003;163:545

  20. Magnitude of Fever • 102°F rule • Most noninfectious disorders in adults are associated with temperatures ≤ 102°F • Best used to exclude noninfectious causes of fever • 106°F • Temperatures ≥ 106°F are rarely due to infection • Examples: central fever, drug fever, NMS, malignant hyperthermia

  21. Causes of FUO in Adults Cunha BA. Fever of unknown origin. Infect Dis Clin North Am 1996;10:111-127.

  22. What is the most common malignancy causing FUO?

  23. Causes of FUO Cunha BA. Fever of unknown origin. Infect Dis Clin North Am 1996;10:111-127.

  24. Causes of FUO Cunha BA. Fever of unknown origin. Infect Dis Clin North Am 1996;10:111-127.

  25. Causes of FUO Cunha BA. Fever of unknown origin. Infect Dis Clin North Am 1996;10:111-127.

  26. Drug Fever • Diagnosis of exclusion • Approximately 10% of fevers in hospitalized patients • Look “well” • Relative bradycardia may occur • Usually no rash • Fever usually returns to normal within 3 days • May take longer if accompanied by a rash ***************************************** Johnson DH, Cunha BA. Drug fever. Infect Dis Clin North Am 1996;10:85-91.

  27. Causes of FUO in Children • Most common infectious etiologies in children: • Bartonella, EBV, CMV, Histoplasmosis, Blastomycosis, TB

  28. What is periodic fever?

  29. Periodic Fever • Periodic is different from sporadic, intermittent, occasional • Periodicity involves having repeated cycles appearing at regular intervals

  30. Periodic Fever Syndromes • Non-familial • PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) • Familial • Familial Mediterranean Fever (FMF) • Hyper IgD Syndrome (HIDS) • TNF-receptor associated periodic syndrome (TRAPS or Hibernian Fever) • Muckle-Wells Syndrome (MWS) • Familial Cold Urticaria (FCU) • Cyclic Hematopoesis (CH)

  31. PFAPA Case Definition Periodic fevers beginning before the age of 5 years At least one clinical criterion (ulcers, pharyngitis, adenitis) Absence of cough, purulent rhinitis, or otitis on examination Asymptomatic periods between attacks Normal growth and development Exclusion of cyclic neutropenia

  32. PFAPA Registry (Vanderbilt) In 1997, parents of registry patients were contacted by telephone to collect information on patients believed by their physicians to have PFAPA 94 patients were available, 83 with long-term follow-up data

  33. Characteristics of PFAPA Patients Thomas KT, et al. J Pediatr. 1999;135:15-21.

  34. PFAPA Symptoms, by Report Thomas KT, et al. J Pediatr. 1999;135:15-21.

  35. Efficacy of Treatment Thomas KT, et al. J Pediatr. 1999;135:15-21.

  36. Familial Periodic Fever Syndromes

  37. What is the diagnostic work up for FUO?

  38. Diagnostic Testing for FUO in Children • First tier • CBC, CMP, blood/urine cultures, ESR/CRP, EBV, CMV, CSD serology, TST • Second tier • Fungal serology; CT chest, abdomen, pelvis with contrast • Third tier • Gallium or Indium scan; bone scan *****************************************

  39. Diagnostic Algorithm for FUO in Adults Complete History and Physical Assessment Order appropriate and specific diagnostic testing Positive Findings Yes No CBC w/ diff, chemistries, LFTs, blood cultures x3, UA, urine culture, ESR, CRP, ANA, RF, HIV ab, PPD, CXR Order appropriate follow-up diagnostic testing Positive Results Yes No CT of chest/abdomen/pelvis with contrast Adapted from Roth AR, Basello GM. Approach to the Adult Patient with fever of unknown origin. Am Fam Physician. 2003;68:2223-8.

  40. Additional Workup for FUO in Adults • If symptoms of “mono” syndrome • CMV antibodies • EBV antibodies • HIV viral load • Toxoplasmosis serologies • If exposure risk factors • Q-fever serology • If abnormal liver enzyme test results • Viral hepatitis serologies Mourad, et al. Arch Intern Med. 2003;163:545

  41. Diagnostic Algorithm for FUO in Adults Assign to most likely category Infection Malignancies Autoimmune Miscellaneous Urine & sputum cultures for AFB, VDRL, HIV test, CMV & EBV serology Hematologic Nonhematologic RF, ANA Order appropriate diagnostic tests based on information from history Mammography, Chest CT with contrast, Upper/lower endoscopy, bone scan, gallium scan Peripheral smear, SPEP No Dx? No Dx? No Dx? No Dx? TTE/TEE, LP, gallium scan, sinus films BM biopsy Brain MRI; Biopsy of LN, skin lesions, or liver TA biopsy, LN biopsy Roth AR, Basello GM. Approach to the Adult Patient with fever of unknown origin. Am Fam Physician. 2003;68:2223-8.

  42. Diagnostic yield of liver biopsy 14% - 17% Hepatomegaly on exam or abnormal LFT’s not helpful in predicting abnormal biopsy result Complication rate 0.06% - 0.32% Diagnostic yield of bone marrow cultures in immunocompetent individuals 0% - 2% Liver Biopsy & Bone Marrow Biopsy Volk et al. J Clin Pathol 1998;110:150 Riley et al. J Clin Pathol 1995:48:706 Mourand et al. Arch Intern Med 2003;163:545

  43. FUO Prognosis • Determined primarily by the underlying disease • Outcome worst for neoplasms • If undiagnosed after extensive evaluation, adults generally have favorable outcome and fever usually resolves after 4-5 weeks Larson et al. Medicine 1982;61:269

  44. Where is the world’s tallest thermometer?

  45. WORLD'S TALLEST THERMOMETER BAKER, CALIFORNIA *****************************************

  46. Case Presentation- “Connor” • Connor is an 18 month old male with a one year history of periodic fevers to 104. • Between each ‘episode’ the child has grown well and has appeared healthy and active • Occasionally there are uncomplicated URI’s and gastroenteritis, but these episodes seem ‘different.’ • What additional information would you like to obtain from Connor’s parents?

  47. Case Presentation- “Connor” • During each episode, his parents report that he has pharyngitis and aphthous ulcers in the mouth. • What disease do you think Connor has and how would treat him?

  48. PFAPA • Treatment is with prednisone 2mg/kg as a single dose at the beginning of each episode. • Rarely, children will require a second dose 24 hrs later. • Treatment typically results in immediate resolution of fever and other symptoms. • Primary side effect of treatment is shortening of the interval between episodes. • PFAPA typically spontaneously resolves prior to adolescence.

  49. Case Presentation- “Kyle” • Kyle is a 7 year old male with daily fever to 103 for 3 weeks and a 10-pound weight loss. He denies other symptoms. • He reports no unusual exposures or travel. He attends 2nd grade. • On examination, his temperature is 104. There are no focal findings, though there is a hint of abdominal discomfort. • How would you proceed with his work-up?

  50. Case Presentation- “Kyle” • CBC WNL. EBV and CMV titers c/w past infection. • ALT 60. AST 36. • ESR 52. CRP 9 (nml < 10). • Abdominal ultrasound normal. • What additional work up would you consider at this time?

More Related