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Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
Pyrexia of unknown origin
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Pyrexia of unknown origin

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Pyrexia of unknown origin

Pyrexia of unknown origin

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  • 1. Pyrexia of Unknown Origin PUO or FUO Dr.T.V.Rao MD1/19/2013 Dr.T.V.Rao MD 1
  • 2. What is the normal human body temperature?A. 37.5 CB. 98.6 FC. Each human being is a unique individual, and therefore, normal temperature cannot be defined.1/19/2013 Dr.T.V.Rao MD 2
  • 3. What is the normal human body temperature?A. 37.6 CB. 98.6 FC Each human being is a unique individual, and therefore, normal temperature cannot be defined.1/19/2013 Dr.T.V.Rao MD 3
  • 4. Normal Body Temperature• For healthy individuals 18 to 40 years of age, the mean oral temperature is 36.8° ± 0.4°C (98.2° ± 0.7°F)• Low levels occur at 6 A.M. and higher levels at 4 to 6 P.M.• The maximum normal oral temperature is 37.2°C (98.9°F) at 6 A.M. and 37.7°C (99.9°F) at 4 P.M.• These values define the 99th percentile for healthy individuals.1/19/2013 Dr.T.V.Rao MD 4 Mackowiak, et al., JAMA 1992;268:1578
  • 5. Definition• Fever > 38.3 on several occasions• Fever lasting more than 3 weeks• No diagnosis despite 1 week of inpatient workup1/19/2013 Dr.T.V.Rao MD 5
  • 6. Terminology• Old Definition: 1. Fever higher than 38.3oC on several occasions. 2. Duration of fever – 3 weeks 3. Uncertain diagnosis after one week of study in hospital• New Definition: – Eliminated the in-hospital evaluation requirements → 3 outpatient visits, or 3 days in hospital. … Ambulatory as well as in1/19/2013 hospital Dr.T.V.Rao MD 6
  • 7. 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 intestines1/19/2013 Dr.T.V.Rao MD 7
  • 8. Definition Expansion1. Classical PUO2. Nosocomial PUO3. Neutropenia PUO4. HIV-Associated5. Transplant1/19/2013 Dr.T.V.Rao MD 8
  • 9. Categories of FUOFeature Nosocomial Neutropenic HIV-associated ClassicPatient’s Hospitalized, Neutrophil count Confirmed HIV- All others withsituation acute care, no either <500/µL or positive fevers for ≥3 infection when expected to weeks admitted reach that level in 1-2 daysDuration of 3 daysb 3 daysb 3 daysb (or 4 3 daysb or 3+illness while weeks as outpatientinvestigated outpatient) visitsExamples Septic Perianal infection, MAIc infection, Infections, thrombophlebitis, aspergillosis, TB, non- malignancy, sinusitis, C. candidemia Hodgkin’s inflammatory difficile colitis, lymphoma, drug diseases, drug drug fever fever fever aAllrequire temperatures of ≥38.3 C (101 F) on several occasions. bIncludes at least 2 days’ incubation of microbiology cultures. cM. avium/M. intracellulare. 1/19/2013 Modified Dr.T.V.Rao Durack, AC Street, in JS Remington, MN Swartz (eds): 9 from DT MD Current Clinical Topics in Infectious Diseases. Cambridge, MA, Blackwell, 1991.
  • 10. Pattern of Fever1/19/2013 Dr.T.V.Rao MD 10
  • 11. Etiologies of PUO• Infection: Three major causes• Abscess .. especially occult ..• Intracellular organisms. (salmonella mycobacterium, bruc ella)• Intravascular … SBE1/19/2013 Dr.T.V.Rao MD 11
  • 12. “True Fever”• Occurs when IL-1, IL-6, TNF-ά or other cytokines are released from monocytes and macrophages in response to infection, tissue injury, drugs, and other inflammatory processes, increasing the body’s set point. The anterior hypothalamus maintains an inherent set point near 36ºC(98.6ºF).• Normal circadian rhythm, which is highest(up to 2ºC, 3ºF) ~6pm and lowest at 6am. This accounts for increased volume of ER visits that peaks in the evening. Most true fevers follow this diurnal pattern.
  • 13. Infectious Causes of FUO• Intraabdominal abscess (liver, splenic, psoas, etc)• Appendicitis, cholecystitis, tubo-ovarian abscess, pyometra• Intracranial abscess, sinusitis, dental abscess• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint prosthesis, pyelonephritis, prostatitis1/19/2013 Dr.T.V.Rao MD 13
  • 14. Infectious Causes of FUO• Intraabdominal abscess (liver, splenic, psoas, etc)• Appendicitis, Cholecystitis, tubo-ovarian abscess, pyometra• Intracranial abscess, sinusitis, dental abscess• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint prosthesis, pyelonephritis, prostatitis1/19/2013 Dr.T.V.Rao MD 14
  • 15. Infectious Causes of FUO• Intraabdominal abscess (liver, splenic, psoas, etc)• Appendicitis, Cholecystitis, tubo-ovarian abscess, pyometra• Intracranial abscess, sinusitis, dental abscess• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint prosthesis, pyelonephritis, prostatitis1/19/2013 Dr.T.V.Rao MD 15
  • 16. Bacterial Pyrogens• Lipopolysaccharide (LPS) endotoxin Endotoxin binds to LPS-binding protein and is transferred to CD14 on macrophages, which stimulates the release of TNFα.• Staphylococcus aureus enterotoxins1/19/2013 Dr.T.V.Rao MD 16
  • 17. Infectious Causes of FUO• Tuberculosis, Mycobacterium avium complex, syphilis, Q fever, Legionellosis• Salmonellosis (including typhoid fever), Listeriosis, ehrlichiosis,• Actinomycosis, nocardiosis, Whipple’s disease• Fungal (candidaemia, cryptococcosis, sporotrichosis, Aspergillosi s, Mucormycosis, Malassezia furfur)• Malaria, Babesiosis, toxoplasmosis, schistosomiasis, fasci oliasis, Toxocariasis, amoebiasis, infected hydatid cyst, trichinosis, trypanosomiasis• Cytomegalovirus, HIV, Herpes simplex, Epstein-Barr virus, parvovirus B191/19/2013 Dr.T.V.Rao MD 17
  • 18. Miscellaneous Causes of FUO• Complex partial status epilepticus, cerebrovascular accident, brain tumor, encephalitis• Drug fever, Sweet’s syndrome, familial Mediterranean fever• Gout, pseudo gout• Kawasaki’s syndrome, Kikuchi’s syndrome• Crohn’s disease, ulcerative colitis, sarcoidosis, granulomatous hepatitis• Deep vein thrombosis• Atelectasis?1/19/2013 Dr.T.V.Rao MD 18
  • 19. Bacterial Pyrogens• Staphylococcus aureus toxic shock syndrome toxin (TSST) Both Staphylococcus toxins are super antigens and activate T cells leading to the release of interleukin (IL)-1, IL-2, TNFα and TNFβ, and interferon (IFN)-gamma in large amounts• Group A and B streptococcal toxins Exotoxins induce human mononuclear cells to synthesize not only TNFα but also IL1 and IL-61/19/2013 Dr.T.V.Rao MD 19
  • 20. CAUSES CLASSIC PUO• INFECTIVE 20-30%• CANCER 10-20%• AUTOIMMUNE 15-20%• MISC 15-25%• UNDIAGNOSED 5-10%1/19/2013 Dr.T.V.Rao MD 20
  • 21. Classic FUO•Infection•Malignancy•Collagen vascular diseases1/19/2013 Dr.T.V.Rao MD 21
  • 22. Infectious Causes of FUO• Intraabdominal abscess (liver, splenic, psoas, etc)• Appendicitis, cholecystitis, tubo-ovarian abscess, pyometra• Intracranial abscess, sinusitis, dental abscess• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint prosthesis, pyelonephritis, prostatitis1/19/2013 Dr.T.V.Rao MD 22
  • 23. Infectious Causes of FUO• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint1/19/2013 Dr.T.V.Rao MD 23
  • 24. Infectious Causes of FUO• Intraabdominal abscess (liver, splenic, psoas, etc)• Appendicitis, cholecystitis, tubo-ovarian abscess, pyometra• Intracranial abscess, sinusitis, dental abscess• Chronic pharyngitis, tracheobronchitis, lung abscess• Septic jugular phlebitis, mycotic aneurysm, endocarditis, intravenous catheter infection, vascular graft infection• Wound infection, osteomyelitis, infected joint prosthesis, pyelonephritis, prostatitis1/19/2013 Dr.T.V.Rao MD 24
  • 25. Geography Malaria Saudi (malaria area)/Africa/India Brucella Saudi/Gulf Area Kala-Azar Yemen/Jazan/Sudan/India Leprosy Yemen/Najran… Typhoid India/Pakistan/Egypt/Indonesia Histoplasmosis USA … (West Coast) N.B.: Ease of Travel → Infection → All parts of the world. Tuberculosis Liver Abscess All over the world. AIDS1/19/2013 Dr.T.V.Rao MD 25
  • 26. 1/19/2013 Dr.T.V.Rao MD 26
  • 27. Pathophysiology• Meningitis and sepsis are serious etiologies of fever in infants and young children.• Neonates immature immune systems place them at greater risk of systemic infection. Hematogenous spread of infection is most common in this age group or in patients who are immunocompromised. For these same reasons, infants who have a focal bacterial infection have a greater risk of developing sepsis.1/19/2013 Dr.T.V.Rao MD 27
  • 28. Bacterial Pyrogens• Lipopolysaccharide (LPS) endotoxin Endotoxin binds to LPS-binding protein and is transferred to CD14 on macrophages, which stimulates the release of TNFα.• Staphylococcus aureus enterotoxins• Staphylococcus aureus toxic shock syndrome toxin (TSST) Both Staphylococcus toxins are super antigens and activate T cells leading to the release of interleukin (IL)-1, IL-2, TNFα and TNFβ, and interferon (IFN)-gamma in large amounts• Group A and B streptococcal toxins Exotoxins induce human mononuclear cells to synthesize not only TNFα but also IL1 and IL-61/19/2013 Dr.T.V.Rao MD 28
  • 29. What are common Causes • The following are among the most common bacterial etiologies of serious bacterial infection in this age group:• Streptococcus pneumoniae• Group B streptococci• Neisseria meningitidis• Haemophilus influenzae type b• Listeria monocytogenes• Escherichia coli1/19/2013 Dr.T.V.Rao MD 29
  • 30. Consequences of Fever can be confusing• Approximately 2.5-3% of highly febrile children younger than 3 years develop occult bacteremia, which typically is caused by S pneumoniae. Viral infections are common in the young child as well; however, exclude serious bacterial infection prior to assuming a viral etiology for the fever.1/19/2013 Dr.T.V.Rao MD 30
  • 31. History Taking• Family History: – Scrutinized for possible infectious or hereditary disorders • Tuberculosis • FMF• Past Medical Condition: Lymphoma → may recur Rheumatic Fever → may recur Still’s Disease → may recur Behcet’s Disease → may recur• Exposure to sexual partner … Acute HIV• Illicit drug abuse (IV) … infective endocarditis, Hepatitis … HIV1/19/2013 Dr.T.V.Rao MD 31
  • 32. Physical Examination….. Looking for the KEY physical sign …. Diagnostic yield60% in children (50%repeated)• Document the Fever: – Significant and persistent for more than ONE occasion.• Analyzing the Pattern: – Neither specific Nor sensitive enough to be considered diagnostic … EXCEPT Tertian & Quarter Pattern → Malaria Pel-Ebstein Pattern → Lymphoma/ Tuberculosis Pulse-Temp Dissociation → Typhoid/ Brucellosis1/19/2013 Dr.T.V.Rao MD 32
  • 33. Infections• Tuberculosis (especially extrapulmonary) Abdominal abscesses Pelvic abscesses Dental abscesses Endocarditis Osteomyelitis 1/19/2013 Dr.T.V.Rao MD 33
  • 34. Infections• Sinusitis Cytomegalovirus Epstein-Barr virus Human immunodeficiency virus Lyme disease Prostatitis Sinusitis1/19/2013 Dr.T.V.Rao MD 34
  • 35. Etiologies of PUO• Infection – Tuberculosis: .. Disseminated • The single most common infection in most PUO series except in children and elderly. • Usually extrapulmonary or military, or • Occurs in the lungs and significant pre-existing lung disease. • Pulmonary TB in AIDS is often subtle (normal chest x- rays → 15 – 30%). • PPD is (+ve) < 50% of TB with PUO. • Diagnosis often requires Bx of LN/Liver/Bone marrow. • Sputum smear (+) only 25%1/19/2013 Dr.T.V.Rao MD 35
  • 36. Etiologies of PUO – Abscess: • Usually located in abdomen or pelvis. • Secondary to appendicitis or diverticulitis. • Pyogenic liver abscess usually follow biliary tract dis./abd. Suppuration. • Amoebic liver abscess is similar to pyogenic → amoebic serology is positive > 95% of cases. • Splenic abscess is usually secondary to hematogenous seeding. • Perinephric or renal abscess is usually secondary to UTI.1/19/2013 Dr.T.V.Rao MD 36
  • 37. Etiologies of PUO – Bacterial Endocarditis • Culture remains negative in 5% of patient. • Culture negative is likely with the following organisms: – Coxiella burnetii → no growth. – HACEK group → incubate blood 7 – 21 days – Brucella } Special media/ – Legionelle } long time – Mycoplasm/Chlamydia } – Fungal → usually sterile • Peripheral signs may not be detected. • Right-side Endocarditis → Lack murmurs → self antibiotics → growth (-ve).1/19/2013 Dr.T.V.Rao MD 37
  • 38. Etiologies of PUO• Infection – Tuberculosis: .. Disseminated • The single most common infection in most PUO series except in children and elderly. • Usually extra pulmonary or military, or • Occurs in the lungs and significant pre-existing lung disease. • Pulmonary TB in AIDS is often subtle (normal chest x- rays → 15 – 30%). • PPD is (+ve) < 50% of TB with PUO. • Diagnosis often requires Bx of LN/Liver/Bone marrow. • Sputum smear (+) only 25%1/19/2013 Dr.T.V.Rao MD 38
  • 39. Geography Malaria Saudi (malaria area)/Africa/India Brucella Saudi/Gulf Area Kala-Azar Yemen/Jazan/Sudan/India Leprosy Yemen/Najran… Typhoid India/Pakistan/Egypt/Indonesia Histoplasmosis USA … (West Coast) N.B.: Ease of Travel → Infection → All parts of the world. Tuberculosis Liver Abscess All over the world. AIDS1/19/2013 Dr.T.V.Rao MD 39
  • 40. HIV associated PUO• HIV alone• TB,M avium/intracelulare• Toxoplasmosis• CMV ,PCP ,Salmonella• Cryptococcus, Histoplasmosis• Non Hodgkins Lymphoma• Drug induced1/19/2013 Dr.T.V.Rao MD 40
  • 41. Malignancies• Chronic leukemia Lymphoma Metastatic cancers Renal cell carcinoma Colon carcinoma Hepatoma Myelodysplastic syndromes Pancreatic carcinoma Sarcomas1/19/2013 Dr.T.V.Rao MD 41
  • 42. Autoimmune Conditions with Fever• Adult Stills disease Polymyalgia rheumatic Temporal arteritis Rheumatoid arthritis Rheumatoid fever Inflammatory bowel disease Reiters syndrome Systemic lupus erythematous Vasculitides1/19/2013 Dr.T.V.Rao MD 42
  • 43. Miscellaneous• Drug-induced fever Complications from cirrhosis Factitious fever Hepatitis (alcoholic, granulomatous, or lupoid) Deep venous thrombosis Sarcoidosis1/19/2013 Dr.T.V.Rao MD 43
  • 44. Diagnosis• A cost-effective individualized approach is essential in the evaluation of these patients to prevent performing inappropriate tests.1/19/2013 Dr.T.V.Rao MD 44
  • 45. Minimal Initial Diagnostic Workup For FUO• Comprehensive history• Physical examination• CBC + differential• Blood film reviewed by hematopathologist• Routine blood chemistry• UA and microscopy• Blood (x 3) and urine cultures• Antinuclear antibodies, rheumatoid factor• HIV antibody• CMV IgM antibodies; heterophile antibody test (if c/w mono-like syndrome)• Q-fever serology (if risk factors)• Chest radiography• Hepatitis serology (if abnormal LFTs)1/19/2013 Dr.T.V.Rao MD 45 Mourad, et al. Arch Intern Med. 2003;163:545
  • 46. Diagnostic TestingBlind application leads to excessive falsetests …• Complete Blood Count – Anemia if present → suggest a serious underlying disease – Leukocytosis with bands → occult bacterial infection – Lymphocytosis & atypical Lymphocyte → Infectious mononucleosis – Leucopenia and Lymphopenia → advanced HIV – Leukoerythroblastic Anemia → Disseminated TB – Thrombocytopenia → Malaria/Leukemia – Peripheral Blood → Malaria1/19/2013 Dr.T.V.Rao MD 46
  • 47. Diagnostic Testing• Urinalysis, Urine Culture, U/E, LFT• ESR – If elevated → significant inflammatory process – Greatest use in establishing a serious underlying disease, esp. if v. high → ESR > 100 mm/h … Tuberculosis … m myeloma … temporal arteritis1/19/2013 Dr.T.V.Rao MD 47
  • 48. Diagnostic Testing – 58% → malignancy → Lymphoma/myeloma – 25% • Infection – Endocarditis • Giant cell arteritis – ↑ High ESR → lacks specificity: • Drug Reaction } • Thrombophlebitis } may cause very high ESR • Nephrotic Syndrome } – Normal ESR → significant inflammatory process is absent with exception.1/19/2013 Dr.T.V.Rao MD 48
  • 49. Diagnostic Testing• CRP-closely associated with inflammatory process – Not invariable components of the febrile response. – Usually does not go up with viral infection. * ESR & CRP is elevated in: 1. Bacterial Infection 2. Neoplasm 3. Immunological-mediated inflammatory states 4. Tissue infarction1/19/2013 Dr.T.V.Rao MD 49
  • 50. Diagnostic Testing• Acute Phase Proteins Proteins Increased Proteins Decreased Fibrinogen Albumin Ferritin Transferrin Plasminogen Alpha- Fetoprotein Protein S Cerruloplasmin New England J Med. 1999, 340.448-4541/19/2013 Dr.T.V.Rao MD 50
  • 51. Diagnostic Testing• Blood Testing – Anti-nuclear Antibodies – Rheumatoid Factor – CMV Antibody … IgM – Heterophile Antibody Test in children and young adult – Tuberculin Skin Test … 5 unit ID – Thyroid Function Test – HIV Screening1/19/2013 Dr.T.V.Rao MD 51
  • 52. Diagnostic Testing• Imaging Studies: … to localize abnormalities for definite tests or treatment – Chest x-ray: • Military shadows → disseminated tuberculosis • Atelectasis } 1. Liver ↑ Hemi diaphragm } Abscess 2. Spleen Pleural Effusion } 3. Pancreatic 4. Subphrenic • Mediastinal mass → Lymphoma/Tuberculosis/ Sarcoid • If CXR is (N) → Repeat on weekly basis1/19/2013 Dr.T.V.Rao MD 52
  • 53. Diagnostic Testing – CT-Scan → CT scan chest • Mediastinal mass → Tuberculosis/Lymphoma/ Sarcoidosis • Dorsal Spine → Spondylitis and disc space disease • CT-Scan Abdomen → very effective to visualize – All types of abscesses – Retroperitoneal tumor, lymph node or hematoma – MRI: spleen, lymph node and the brain1/19/2013 Dr.T.V.Rao MD 53
  • 54. Diagnostic Testing• Serology Test – Brucella Titer – CMV & EBV antibody test – HIV testing (Elisa screening) – ANF• Radio nuclear Scanning – Bone TC-scan → osteomyelitis (skeletal) – Gallium scan → occult inflammation – Indium labeled WBC-scan → occult abscesses1/19/2013 Dr.T.V.Rao MD 54
  • 55. Diagnostic Testing – Hepatomegaly or Abnormal LFT • Hepatic Granuloma – Non-caseating: Tuberculosis/Sarcoidosis & Brucellosis – Caseating: Tuberculosis – Bone Marrow • Granuloma ± Tubercle Bacilli → Tuberculosis • Aplastic Cells → Leukemia • Leishmania Bodies → Kala-Azar • Atypical Cells → Lymphoma • Atypical Plasma Cells → M. myeloma – Temporal Artery → Giant Cell Arteritis – Pleural or Pericardial → Extrapulmonary Tuberculosis1/19/2013 Dr.T.V.Rao MD 55
  • 56. Investigation• Blood culture before the antibiotics• Culturing of Urine• Sputum culture• Stool examination for Bacterial and Parasitic infection.1/19/2013 Dr.T.V.Rao MD 56
  • 57. Etiologies of PUO – Abscess: • Usually located in abdomen or pelvis. • Secondary to appendicitis or diverticulitis. • Pyogenic liver abscess usually follow biliary tract dis./abd. Suppuration. • Amoebic liver abscess is similar to pyogenic → amoebic serology is positive > 95% of cases. • Splenic abscess is usually secondary to haematogenous seeding. • Perinephric or renal abscess is usually secondary to UTI.1/19/2013 Dr.T.V.Rao MD 57
  • 58. Tuberculosis• Sputum examination for AFB• Culturing for AFB• Monteux test Tuberculin test• X ray of the chest1/19/2013 Dr.T.V.Rao MD 58
  • 59. Diagnosis• More invasive testing, such as LP or biopsy of bone marrow, liver, or lymph nodes, should be performed only when clinical suspicion shows that these tests are indicated or when the source of the fever remains unidentified after extensive evaluation.• When the definitive diagnosis remains elusive and the complexity of the case increases, an infectious disease, rheumatology, or oncology consultation may be helpful.1/19/2013 Dr.T.V.Rao MD 59
  • 60. Etiologies of PUO• Factitious Fever Febrile PUO In one study … 9% of cases of PUO – False fever: thermometer manipulation using external heat or substitute thermometer. Men use this way … physician are rare for this disorder. Increasing somewhat in elderly … 115 … 116 … – Genuine fever (self induced) Administration of pyrogenic substances (bacterial suspensions) Generally young women with connection to health care …1/19/2013 often NURSES. Dr.T.V.Rao MD 60
  • 61. Pyrexia of Unknown Origin The majority of disease remaining after an initial NEGATIVE work-up are: 1. Neoplasm 2. Seronegative Collagen Vascular Disease 3. Increasing Tuberculosis 4. Increasing Drug Addition 5. Elderly with Endocarditis 6. HIV with or without infection or malignancy 7. Implanted prosthetic devices 8. Travel … New Exposure1/19/2013 Dr.T.V.Rao MD 61
  • 62. Therapeutic Trials• Limitation and risk of empirical therapeutic trials: – Rarely specific – Underlying disease may remit spontaneously false impression of success. – Disease may respond partially and this may lead to delay in specific diagnosis. – Side effect of the drugs can be misleading.1/19/2013 Dr.T.V.Rao MD 62
  • 63. Therapeutic Trials• What is the best therapy for PUO patient? – To hold therapeutic trials in the early stage… except in: • Patient who is very sick to wait. • All tests have failed to uncover the etiology.1/19/2013 Dr.T.V.Rao MD 63
  • 64. Prognosis• Prognosis is determined primarily by the underlying disease.• Outcome is worst for neoplasms.• FUO patients who remain undiagnosed after extensive evaluation generally have a favorable outcome and the fever usually resolves after 4-5 weeks.1/19/2013 Dr.T.V.Rao MD 64 Larson et al. Medicine 1982;61:269
  • 65. Summary• FUO is often a diagnostic dilemma• Infections comprise ~30% of cases• Bone marrow biopsies are of low diagnostic yield• Diagnostic approach should occur in a step-wise fashion based on the H&P• Patient’s that remain undiagnosed generally have a good prognosis1/19/2013 Dr.T.V.Rao MD 65
  • 66. • Programme Created By Dr.T.V.Rao MD for Medical Students in the Developing World • Email • doctortvrao@gmail.com1/19/2013 Dr.T.V.Rao MD 66

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