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Fever of Undetermined Origin

Fever of Undetermined Origin

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SUBJECT:
Medicine 2
DATE: July 02, 2008
TOPIC:
Fever of Undetermined Origin
LECTURER:
Mr. Alberto Gabriel
TRANSGROUP:SMV
Page5
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A
DEFINITION
\u2022
Classic definition by Petersdorf &Beeson, 1961
-

An illness that is characterized by a temperature of 38.3\u00b0C or greater on multiple occasions that lasts three weeks or longer, and that remains undiagnosed after one week of in-hospital evaluation.

\u2022
Durack & Street, 1991
-
Proposed a new system of classification of
FUO
* (-) for any laboratory results
Table 1. Modifications of FUO definition by Durack & Street, 1991
CATEGORIES
Diagnostic Categories of FUO
\u2022
Infections \u2013 most common cause of
classical FUO
\ue000
Systemic
\ue000
Localized
\u2022
Neoplasms
\u2022
Collagen-vascular disease
\ue000
Inflammatory diseases
\ue000
CTD, autoimmune diseases
\u2022
Miscellaneous causes
\ue000
Drug fever
\ue000
Pulmonary embolism
\ue000
Factitious fever
\u2022
Undiagnosed
COMMON CAUSES OF CLASSIC FUO
Table 2. Causes of FUO in Adults
Category

Petersd
orf
&
Beeson
(1961)
100
cases

Larson,
Featherslone &
Petersdorf
(1982)
105 cases

Knockaert
Vanneste &
Babbaers
(1992)
187 cases

Klejin
(1997)
167
cases

Infections
36
31
23
26
Malignancy
19
31
7
12.5
Collagen-
vascular disease
15
9
22
24
Others
23
7
23
8
Undiagnosed
7
12
25
30
*Naproxen \u2013 treatment for rheumatic fever
- test after 3 days = (-) fever \u2192 not infectious
(+) fever \u2192 infectious
Table 3. Causes of FUO in Children
Category

Pizzo, et
al.
(1972)
100
cases

Lohr &
Hendley
(1974)
84 cases

Mc
Chung
(1980)
99
cases

Infections
82
33
29
Malignancy
20
18
11
Collagen-vascular
disease
6
13
8
Miscellaneous
10
15
19
Undiagnosed
12
19
32
Table 4. Local Experience (PGH, 1975-1990), unpublished
Number (%)
Infections
34 (46.6)
Malignancy
20 (27.4)
Collagen-vascular (autoimmune)
10 (13.7)
Hypersensitivity
2 (2.7)
Unknown
7 (9.6)
Total
73 (100)
Source: M.F. Mendoza MD, 29th PSMID Conv
Table 5. Diagnostic Categories of 72 Patients with FUO at the Santo
Tomas University Hospital
Number (%)
Infections
44 (61)
Neoplasms
9 (13)
Connective tissue disease
4 (6)
Miscellaneous
3 (4)
Unknown
12 (17)
INFECTIONS

1. TB
2. Abdominal abscess
3. Cryptic abscess
4. Typhoid fever

CLASSIC

IMMUNO-
DEFICIENT
NEUTROPEN

IC

HIV \u2013
ASSOCIAT
ED

NOSOCOMIA
L
Patient
type

Patients not
in other
categories
fever \u2265 3
weeks

Has < 500
neutrophils

Confirmed
HIV
positive

Hospitalized
, Acute
case, No
infection
when
admitted

Duration of
illness
while
under
investigati
on

3 days or
3 OPD visits
3 days

3 days or
4 weeks
as OPD

3 days
Example of
etiology

Infections,
malignanci
es,
inflammato
ry disease

Perianal
infection,
aspergillosis
,
candidemia

MAI, TB,
non-
Hodgkin\u2019s
lymphoma

Septic
thrombo-
phlebitis,
sinusitis, C.
difficile
colitis

SUBJECT:
Medicine 2
DATE: July 02, 2008
TOPIC:
Fever of Undetermined Origin
LECTURER:
Mr. Alberto Gabriel
TRANSGROUP:SMV
Page5
5. Chronic active hepatitis

6. Infective endocarditis
7. Leptospirosis
8. Pyelonephritis
9. Malaria

10. Chronis sinusitis
11. Toxoplasmosis
12. Osteomyelitis
-
Predominant cause in developing countries
-
High in infants and children
-
Vary according to place (country)

Ex. Visceral Leishmaniasis \u2013 Middle East
Melioidosis \u2013 South East Asia & Australia
K Fujimoto Disease \u2013 Japan

- Cervical lymphadenopathy
- Malaise
- Fever
PARASITIC INFECTIONS AS CAUSE OF FUO
- may occur with other concomitant cause
\u2022
Schistosoma
\u2022
Leishmaniasis
\u2022
Toxoplasmosis
\u2022
Others \u2013 Fasciola, Amoeba
MALIGNANCIES & FUO
\u2022
Hematologic and solid tumors:
\ue000
Lymphoma
\ue000
Acute leukemia (children)
\ue000
Hypernephroma (Renal cell CA)
\ue000
Bone sarcoma
\ue000
Atrial myxoma
\ue000
GI \u2013 gastric CA, liver, colon
MALIGNANCY (Neoplasms)
\u2022
Frequency decreasing
\u2022
Higher in elderly
\u2022
More in developed country
\u2022
Infection is secondary
COLLAGEN-VASCULAR DISEASE (Autoimmune)
\u2022
Systemic Lupus Erythematosus
\u2022
Rheumatoid arthritis
\u2022
Systemic vasculitis
\u2022
Mixed connective tissue disease
\u2022

Rheumatic fever (most common due to
presence of Streptococcus
pneumoniae/viridans \u2192 heart valves, kidney)

\u2022
Others e.g. Still\u2019s disease
CONNECTIVE TISSUE DISEASE
\u2022
Young adults \u2013SLE
\u2022
Still\u2019s disease (JRA)
\u2022
Elderly \u2013 Temporal arteritis and Polymyalgia
rheumatica
\u2022
More in developed countries
MISCELLANEOUS CAUSES
\u2022
Pulmonary embolism
\u2022
Chronic hepatitis
\u2022
Other granulomatous diseases
\u2022
CNS causes
\u2022
Cyclic neutropenia
\u2022
Factitious fever
\u2022
GHVD
HYPERSENSITIVITY DISEASES
\u2022
Drug fever
\u2022
Erythema multiforme \u2013 skin infection
\u2022
Allergic vasculitis
\u2022
Serum sickness
\u2022
Milk allergy
\u2022
Halothane sensitization
\u2022
Post-pericardiotomy syndrome
AGENTS COMMONLY ASSOCIATED WITH DRUG-
INDUCED FEVER
\u2022
Allopurinol (Zyloprim)
\u2022
Captopril (Capoten)
\u2022
Cimetidine (Tagamet)
\u2022
Clofibrate (Atromid-S)
\u2022
Erythromycin
\u2022
Heparin
\u2022
Hydralazine (Apresoline)
\u2022
Hydrochlorothiazide (Esidrix)
\u2022
Isoniazid
\u2022
Meperidine (Demerol)
\u2022
Methyldopa (Aldomet)
\u2022
Nifedipine (Procardia)
\u2022
Nitrofurantoin (Furadantin)
\u2022
Penicillin
\u2022
Phenytoin (Dilantin)
\u2022
Procainamide (Pronestyl)
\u2022
Quinidine
HIV-RELATED FUO
\u2022
Opportunistic infections
\ue000
Atypical manifestations
\ue000
Prior antibiotic prophylaxis
\u2022
Mycobacterial infection \u2013 most common in the
Philippines
\u2022
Collagen-vascular \u2013 uncommon
\u2022
Pneumonia \u2013 other countries
NOSOCOMIAL FUO
\u2022
> 48 hours in hospital or at least 3 days before
the start of fever
\u2022
Risk factors
\ue000
Urinary & respiratory instrumentation
\ue000
Surgery
\ue000
IV devices
\ue000
Drugs
\ue000
Immobilization
SUBJECT:
Medicine 2
DATE: July 02, 2008
TOPIC:
Fever of Undetermined Origin
LECTURER:
Mr. Alberto Gabriel
TRANSGROUP:SMV
Page5
-
Fracture in sensitive areas (thigh,
pelvis)
-
ICU
IMMUNODEFICIENT FUO
A. Immunosuppression
\ue000
Infection
\ue000
Atypical manifestation
\ue000
GVHD in transplants
B. Neutropenic
\ue000
Bacteremia & sepsis
\ue000
Fungal infection
COMMON APPROACH TO FUO

FUO General Consideration
1. Well organized systemic approach
2. Age group difference

3.Duration of fever \u2192 > 3 weeks
4. Type of hospital
5. Immune state/underlying diseases
-
DM, collagen problem
Evaluation of FUO
-
Starts with very good history and PE
1. History \u2013 documented fever
\ue000
Recent travel
\ue000
Exposure to pets/animals
\ue000
Work environment
\ue000
Family history
\ue000
Medication
2.PE \u2013 subtle signs and symptoms
\ue000
Nausea
\ue000
Aaaa
\ue000
Oral ulcers
\ue000
Fundoscopy
\ue000
Petechial/splinter hemorrhages
USEFUL LABORATORY EXAMINATIONS
DIAGNOSIS
\u2022
More aggressive and rapid evaluation for
critically ill patients \u2013 as soon as possible
\u2022
Evaluation slow and deliberate (out-patient) for
the chronically ill
EVALUATION OF A PATIENT WITH FUO
A. No obvious cause, systemic symptoms not
disabling
\ue000
OPD work-ups
-
CBC with ESR
-
Urinalysis
-
Chest x-ray
-
Alkaline phosphatase, SGOT
-
ANA, other serologic tests
-
Blood culture
-
Stool for guiac
B.Persistence of fever or clinical deterioration \u2013
hospitalization
1. Repeat tests done in OP setting
2. Blood or BMA C/S
-
3 aerobic and anaerobic in the 1st 2
days of hospitalization
3. PPD test
4. Subsequent tests must be individualized
C. Use of specific test

1. Autoantibody screening
2. Specific PCR
3. Imaging

-
X-ray
-
Isotope scanning
4. Tumor markers
* TB \u2013 cause of prolong fever
DIAGNOSTIC ADVANCES
\u2022
Ultrasonography
\u2022
Echocardiography
\u2022
CT scan
\u2022
Magnetic Resonance Imaging (MRI) \u2013 identify
which part is affected
\u2022
Labelled WBC \u2013 Indium, Technetium
\u2022
Gallium scan
\u2022
Angiography
\u2022
PET scan
\u2022
Venous duplex imaging of LE
Table 6. Diagnostic Categories of 72 Patients with FUO at the Santo
Tomas University Hospital
Chest radiograph
Tuberculosis, malignancy,
Pneumocystis carinii
pneumonia
CT of abdomen or pelvis with
contrast agent
Abscess, malignancy
Gallium 67 scan
Infection, malignancy
Indium-labeled leukocytes
Occult septicaemia
Technetium Tc 99m

Acute infection and
inflammation of bones and
soft tissue

MRI of brain
Malignancy, autoimmune
conditions
PET scan

Malignancy, inflammation
Transthoracic or
transesophageal

echocardiography
Bacterial endocarditis
Venous Doppler study
Venous thrombosis
TUMOR MARKERS
\u2022
Diagnostic
\ue000
\u03b1 feto protein (AFP)
\ue000
\u03b2 HCG
\u2022
Highly supportive
\ue000
C19-9
\ue000
CA125
\ue000
CEA
\ue000
PSA
\u2022
Others
NON SPECIFIC INFLAMMATORY MARKERS
\u2022
Procalcitonin

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