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PYREXIA OF UNKNOWN ORIGIN
Dr. Alaa Jumaa
PUO is
A Common disease presenting ATYPICALLY
Terminology
Old Definition: Petersdorf and Beeson (1961)
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 in hospital
Categories of Illness Causing PUO
Infections 30 - 40 %
Malignancies 20 – 25 %
Collagen Vascular Disease 10 – 20 %
Miscellaneous 15 – 20 %
Undiagnosed 10 – 15 %
Epidemiology and Etiology
1970 → up to date: Infection is the most frequent.
1930 → 70% undiagnosed PUO 2000 → 5-10% undiagnosed PUO
Diagnostic Advances:
Modify the spectrum of PUO causing diseases:1. Serology: HIV / Brucella / SLE
2. Imaging Tech: Abscesses/Solid Tumor
Geography
Malaria Saudi (malaria area)/Africa/India
Brucella Saudi/Gulf Area
Kala-Azar Yemen/Sudan/India
Leprosy Yemen/Najran…
Typhoid India/Pakistan/Egypt/Indonesia
Histoplasmosis USA … (West Coast)
Tuberculosis
All over the world.Liver Abscess
AIDS
9
0
10
20
30
40
50
60
Infect Neopl CVD Other Unknown
India UK
J Postgrad Med 2001; 47(2):104-107
Geography
DIAGNOSIS AND TREATMENT
Diagnostic Approach
Careful History Physical Examination (repeated) Diagnostic Testing
History
Verify the presence of fever:Series of 347 patients → for prolonged fever
→ 35% were ultimately: a. No fever
b. Factitious Fever
Duration of Fever:The longer the duration → the less likely to
have infection and malignancy.
History
A history of exposure to wild or domestic animals should be solicited (zoonotic disease )
Ingestion of dirt is a particularly important clue to infection with Toxoplasma gondii (toxoplasmosis).
Ancestry from the Mediterranean should suggest the possibility of familial Mediterranean fever (FMF).
History
Travel: Travel to an area known to be endemic for certain disease:
Name of the area, duration of stay Onset of illness … (incubation period)
1 – 10 Days 10 – 21 Days Weeks - Months
Malaria Malaria Kala Azar
Plague Typhoid Amoebiasis
Dengue Brucella HIV
Salmonella Hepatitis A Hepatitis
History
Drug and Toxin History:almost all drug can cause drug fever … Antihistaminebeta lactamanti-TB … Salicylates and other NSAID …eye drops, which may be associated with
atropine-induced fever.
History
Localizing Symptoms: May Indicate the source of fever:
Bone ach osteomylitis
Bone Metastasis
Headache Chronic Meningitis
RUQ Pain Liver Abscess
LUQ Pain Splenic Abscess
Subtle changes in behavior Granulomatous Meningitis
History
Family History:search for possible infectious or hereditary
disorders Tuberculosis FMF
Past Medical Condition:Lymphoma → may recurRheumatic Fever → may recur
Physical Examination
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 → MalariaPel-Ebstein Pattern → Lymphoma/TuberculosisPulse-Temp Dissociation → Typhoid/Brucellosis
Pattern of Fever
Physical Examination
Sweating in a febrile child should be noted familial dysautonomia, or exposure to atropine.
A careful ophthalmic examination is important Hyperemia of the pharynx, with or without
exudate, suggests infectious mononucleosis, CMV infection,
toxoplasmosis, salmonellosis ,Kawasaki disease. The muscles and bones should be palpated
carefully.
Physical Examination
Examine for Lymphadenopathy
Cervical Area 1. Lymphoma(Localized) 2. Tuberculosis
3. Infectious Mononucleosis
4. Lymphadenitis (bacterial)
Diagnostic Testing
1. CBC with a differential WBC count and a urinalysis should be part of the initial laboratory evaluation.
2. An erythrocyte sedimentation rate (ESR).
3. C-reactive protein is another acute-phase reactant that becomes elevated and returns to normal more rapidly than the ESR.
Diagnostic Testing
serology1. Anti-nuclear Antibodies
2. Rheumatoid Factor
3. CMV Antibody … IgM
4. Heterophile Antibody Test in children and young adult
5. Tuberculin Skin Test … 5 unit ID
6. Thyroid Function Test
7. HIV Screening
Diagnostic Testing
CulturesBlood
Obtain more than 3 blood cultures from separate venipunctures over 24 hr period if you are suspecting inf. Endocarditis prior antimicrobial use.
Incubate the blood for 4 weeks, to detect the presence of SBE & Brucellosis
Sputum: For TuberculosisAny normal sterile:
CSF/urine/pleural or peritoneal fluid Bone marrow aspirate → Tuberculosis/Brucellosis Lymph node Bx → TB
Diagnostic Testing
Imaging Studies: … to localize abnormalities for definite tests or treatmentChest x-ray:
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 basis
Diagnostic Testing
CT-Scan → CT scan chest Mediastinal mass → Tuberculosis/Lymphoma/
Sarcoidosis CT-Scan Abdomen → very effective to visualize
All types of abscesses Retroperitoneal tumor, lymph node or haematoma
MRI: spleen, lymph node and the brain Radionuclide scans
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. Endocarditis
6. HIV with or without infection or malignancy
7. Implanted prosthetic devices
8. Travel … New Exposure
Therapeutic Trials
Limitation and risk of empirical therapeutic trials:Rarely specificUnderlying 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.
Therapeutic Trials
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. Tuberculosis Culture-negative endocarditis.
THANK YOU