9. Epidemiology and Etiology
Infections 30 - 60 %
Collagen Vascular Disease 20 â 35 %
Malignancies 10 â 20 %
Miscellaneous 15 â 20 %
Undiagnosed 10 â 15 %
Categories of PUO in India
Handa et al
Handa et al
(1996)
D Kejarwal et
al (2001)
Di panjan
Bhandyopadha
yay et al (2011)
Infections 43.8% 53% 53.8%
Collagen Vascular
Disease
15.7% 11% 11%
Neoplasm 8.3% 17% 22%
10. Etiologies of FUO
Infection: Three major causes
īIntracellular organisms. (Salmonella
Mycobacterium, Brucella)
īIntravascular âĻ SBE
īAbscess .. especially occult ..
11. Etiologies of FUO
īInfection- Tuberculosis: .. Disseminated
īˇ Single most common infection in most PUO series
īˇ Usually extrapulmonary or miliary, or
īˇ Occurs in the lungs and significant pre-existing lung
disease.
īˇ Pulmonary TB in HIV is often subtle (normal chest x-
rays 15 â 30%).
â
īˇ PPD is (+ve) < 50% of TB with FUO.
īˇ Diagnosis often requires Bx of LN/Liver/Bone
marrow.
īˇ Sputum smear (+) only15- 25%
12. Etiologies of FUO
Bacterial Endocarditis:
īˇ Culture remains negative in 5-30% of patient.
īˇ Culture negative is likely with the following organisms:
īĸ Coxiella burnetii no growth.
â
īĸ HACEK group incubate blood 7 â 21 days
â
īĸ Brucella } Special media/
īĸ Legionelle } long time
īĸ Mycoplasma/Chlamydia }
īĸ Fungal usually sterile
â
īˇ Peripheral signs may not be detected.
īˇ Right-side Endocarditis Lack murmurs self antibiotics
â â â
growth (-ve).
13. Etiologies of FUO
Abscess:
īˇ Usually located in abdomen or pelvis.
īˇ Secondary to appendicitis or diverticulitis.
īˇ Pyogenic liver abscess usually follow biliary tract dis./abd.
Suppuration.
īˇ Splenic abscess is usually secondary to hematogenous
seeding.
īˇ Perinephric or renal abscess is usually secondary to UTI.
īˇ Subphrenic Abscess
īˇ Retroperitoneal Abscess
īˇ Paravertebral Abscess
14. Etiologies of FUO
īCollagen-Vascular-Disease
You need to recognize the syndrome otherwise no
diagnosis
īĄ SLE
īĄ Stillâs disease (young or adult)â23-50%
īĄ Giant cell arteritis } 15% of PUO
â
īĄ Polymyalgia Rheumatica }
īĄ Behcetâs Disease
īĄ Relapsing polychondritis
15. Etiologies of FUO
īMalignancy
īĄ Lymphoma âĻ Fever is a presenting feature
īĄ Leukemia âĻ M. Myeloma
īĄ Renal cell carcinoma âĻ
īĄ HCC or secondary metastasis to the liver
Benign Neoplasm
16. Etiologies of FUO
īMiscellaneous Causes: (Non-Infectious)
īĄ Vascular Causes:
īˇ Pulmonary Emboli
īĸ 50% are febrile
īĸ Fever is < 39o
C
īĸ Patient typically has predisposing factors cancer or recent
â
immobility.
īˇ Hematoma in closed space
īĸ When it cause PUO usually arise from hemorrhage in the
â
retroperitoneal space or within the wall of an aneurysm or
dissection of the thoracic or abdominal aorta.
17. Etiologies of FUO
Hyperthyroidism
īˇ Occasionally cause PUO most frequently diagnosed clinically.
â
īˇ Often accompanied by weight loss.
Familial Mediterranean Fever
īˇ Recurrent fever
īˇ Arthritis pain out of proportional to signs
īˇ Polyserositis (peritonitis âĻ may be pleuritis)
īˇ Leukocytosis
īˇ Not always hereditary
18. Etiologies of PUO
īFactitious Fever
Febrile PUO
In one study âĻ 9% of cases of PUO
īĄ False fever: thermometer manipulation using external
heat or substitute thermometer.
īĄ H/O Psychiatric illness
īĄ Increasing somewhat in elderly âĻ
Generally young women with connection to health care
âĻ often NURSES.
23. History
īVerify the presence of fever:
īĄDuration & Pattern of Fever
Tertian & Quartian Patternâ Malaria
Pel-Ebstein Pattern â Lymphoma
Pulse-Temp Dissociation â Typhoid/Brucellosis
24. History
īFamily History:
īĄ Scrutinized for possible infectious or hereditary
disorders
īˇ Tuberculosis
īˇ FMF
īPast Medical Condition:
Lymphoma,Rheumatic Fever,Stillâs Disease,Behcetâs
Disease may recur
â
Travel History
Work Environment
īExposure to sexual partner âĻ HIV, Syphilis
īIllicit drug abuse (IV) âĻ Infective endocarditis,
Hepatitis âĻ HIV
27. Physical Examination
īExamine the Skin:
īĄ Rash:
īˇ SLE âĻ.. All types of rashes is described
īˇ Stillâs Disease Evanescent erythematous rash over the trunk
īˇ Infective Endocarditis (Janewayâs lesion)
īˇ Typhoid Fever âĻ rose spots over abdomen
īĄ Oslerâs Nodes: Painful nodule on the pads of toes & fingers â
Infective Endocarditis
28. Physical Examination
īExamine for Oral Ulcer
īĄ SLE
īĄ Behcetâs Syndrome
īExamine for Arthritis
īExamine the Fundus
īĄ Rothâs spots (white-centered haemorrhage) Infective
â
Endocarditis
īĄ Yellowish-white choroidal lesion Tuberculosis
â
īĄ Choriodoretinitis Active Toxo or CMV in HIV patient.
â
30. Diagnostic Testing-Initial Workup
īComplete Blood Count
īĄ Anemia if present Suggest a serious underlying
â
disease
īĄ Leukocytosis with bands Occult bacterial infection
â
īĄ Leucopenia and Lymphopenia Advanced HIV
â
īĄ Leukoerythroblastic Anemia Disseminated TB
â
īĄ Thrombocytopenia Malaria/Leukemia
â
īĄ Peripheral Blood Malaria
â
31. Diagnostic Testing
ī ESR
īĄ If elevated significant inflammatory process
â
īĄ Greatest use in establishing a serious underlying disease,
esp. if v. high ESR > 100 mm/h âĻ
â
Tuberculosis,Myeloma,Temporal arteritis
īCRP-closely associated with inflammatory process
âĸ ESR & CRP is elevated in:
âĸ 1.Bacterial Infection 2. Neoplasm
3.Immunological-mediated inflammatory states
4.Tissue infarction
33. Diagnostic Testing- Second Evaluation
īBlood Testing
īĄ Anti-nuclear Antibodies
īĄ Rheumatoid Factor
īĄ CMV & EBV Antibody âĻ IgM
īĄ Brucellosis AB titre
īĄ Thyroid Function Test
īĄ HIV Screening
34. Diagnostic Testing- Second Evaluation
īĄ CT-Scan CT scan chest
â
īˇ Mediastinal mass Tuberculosis/Lymphoma/ Sarcoidosis
â
īˇ Dorsal Spine Spondylitis and disc space disease
â
īˇ CT-Scan Abdomen very effective to visualize
â
īĸ All types of abscesses
īĸ Retroperitoneal tumor, lymph node or haematoma
īĄ ECHO
īĄ Bone Marrow Aspiration & Culture
īĄ Colonoscopy & Biopsy
īĄ Radionucletide scans
īĄ PET scan
35. Therapeutic Trials
īLimitations and risk of empirical therapeutic trials:
īĄ Rarely specific
īĄ Underlying disease may remit spontaneously false
impression of success.
īĄ Disease may respond partially and this may lead to delay in
specific diagnosis.
īĄ Side effect of the drugs can be misleading.
36. Therapeutic Trials
īAntimicrobial Trials:
īĄ Expected to suppress, but not cure, an infectious process
such as abscess may have false feeling of response.
â
īĄ Failure to have quick response does not mean wrong
â
diagnosis:
īˇ Endocarditis
īˇ Pelvic inflam. Disease
īˇ Typhoid Fever
Start early in certain conditions- Cirrhosis , Asplenia ,
Biologic Therapy, on Immuno Suppressive,Travel
Exposure
38. Therapeutic Trials
īEmpiric drug trial for suspected T.B:
īĄ Presence of granuloma on Bx before culture result.
īĄ Elderly or immunocompromised patient with (+ve) TB skin
test and deteriorating clinical condition.
īĄ No drug for stable patient without any suggestive features
laboratory result.
39. Therapeutic Trials
īEmpiric drug trial for suspected culture:
ī
(-ve) Endocarditis:
īĄ Patient with new or changing murmur or peripheral signs of
endocarditis.
40. Therapeutic Trials
īEmpiric drug trials for suspected Vasculitis:
īĄ Elderly with weight loss and any symptoms suggestive
(headache, visual disturbance, jaw claudication) and ESR >
â
50 mm/hr â
īĄ Patient above 50 yrs who is c/o muscle pain and stiffness
around hip and shoulder with ESR
â â
īĄ Ongoing vasculitis
Dramatic response is enough to establish the DX.
NSAIDS & Colchichine
41. Prognosis
īIt depends on:
īĄ Cause of fever
īĄ Nature of the underlying disease(s) BUT .. Generally
poor in:
īˇ Elderly
īˇ Neoplasm
īDiagnostic delay has adverse effect in:
īĄ Intra Abdominal Infection
īĄ Miliary Tuberculosis
īĄ Recurrent Pulmonary Emboli
īĄ Disseminated Fungal Infection
īĄ Temporal Arteritis
42. Outcome
īIf the cause of fever remains elusive repeat history
â
and examination.
ī5 â 15% of cases The diagnosis remain obscure.
â
However, most of these patients defervesce without
treatment no disease later.
â
57. Etiologies of PUO
īAlcoholic Hepatitis
īĄ Often unsuspected pt. deny
â
īĄ Fever is usually low grade < 38.5o
C
īĄ May have jaundice and hepatomegaly.
īĄ AST > ALT 2:1 AST < 500
â
īĄ Leukocytosis is often there.
īĄ If you do not think about it in the right time and with the
right patient âĻ then you will be troubled and will work a lot
in order to get the etiology.
58. Diagnostic Testing
īĄ â High ESR lacks specificity:
â
īˇ Drug Reaction }
īˇ Thrombophlebitis } may cause very high ESR
īˇ Nephrotic Syndrome }
īĄ Normal ESR significant inflammatory process is
â absent with
exception.
59. Diagnostic Testing
īLaparoscopy
īĄ To visualize and biopsy the pathology in the abdomen
suggestive of:
e.g. Tuberculous peritonitis
Peritoneal carcinomatosis
īBiopsy
īĄ Enlarged lymph node
īˇ Granulomatous disease (Tuberculosis)
īˇ Metastatic carcinoma
īˇ Others
61. Diagnostic Testing
īCultures
īĄ Blood
īˇ Obtain more than 3 blood cultures from separate venipunctures
over 24 hr period if you are suspecting inf. Endocarditis prior
antimicrobial use.
īˇ Incubate the blood for 4 weeks, to detect the presence of SBE &
Brucellosis
īĄ Sputum: For Tuberculosis
63. Management of FUO
īWithhold therapy until the cause is found
īExceptions:
īĄ Neutropenic Fever
īĄ Unstable hospitalized patient
īĄ Corticosteroids in suspected Temporal Arteritis
īĄ HIV Patients