pyrexia of unknown origin dr. alaa jumaa puo is a common disease presenting atypically
TRANSCRIPT
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PYREXIA OF UNKNOWN ORIGIN
Dr. Alaa Jumaa
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PUO is
A Common disease presenting ATYPICALLY
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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
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Categories of Illness Causing PUO
Infections 30 - 40 %
Malignancies 20 – 25 %
Collagen Vascular Disease 10 – 20 %
Miscellaneous 15 – 20 %
Undiagnosed 10 – 15 %
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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
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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
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Infect Neopl CVD Other Unknown
India UK
J Postgrad Med 2001; 47(2):104-107
Geography
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DIAGNOSIS AND TREATMENT
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Diagnostic Approach
Careful History Physical Examination (repeated) Diagnostic Testing
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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.
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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).
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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
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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.
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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
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History
Family History:search for possible infectious or hereditary
disorders Tuberculosis FMF
Past Medical Condition:Lymphoma → may recurRheumatic Fever → may recur
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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
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Pattern of Fever
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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.
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Physical Examination
Examine for Lymphadenopathy
Cervical Area 1. Lymphoma(Localized) 2. Tuberculosis
3. Infectious Mononucleosis
4. Lymphadenitis (bacterial)
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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.
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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
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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
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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
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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
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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
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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.
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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.
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