PYREXIA OF UNKNOWN ORIGIN

1. PYREXIA OF UNKNOWN ORIGIN Dr. AlaaJumaa

2. PUO is A Common disease presenting ATYPICALLY

5. Terminology • Old Definition: Petersdorf and Beeson (1961) • Fever higher than 38.3oC on several occasions. • Duration of fever – 3 weeks • 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

6. Categories of Illness Causing PUO

7. 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: • Serology: HIV / Brucella / SLE • Imaging Tech: Abscesses/Solid Tumor

8. Geography

9. Geography J Postgrad Med 2001; 47(2):104-107

10. DIAGNOSIS AND TREATMENT

11. Diagnostic Approach • Careful History • Physical Examination (repeated) • Diagnostic Testing

12. 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.

13. 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).

14. 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)

15. History • Drug and Toxin History: • almost all drug can cause drug fever … • Antihistamine • beta lactam • anti-TB … • Salicylates and other NSAID … • eye drops, which may be associated with atropine-induced fever.

16. History • Localizing Symptoms: • May Indicate the source of fever:

17. History • Family History: • search for possible infectious or hereditary disorders • Tuberculosis • FMF • Past Medical Condition: Lymphoma → may recur Rheumatic Fever → may recur

18. 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 → Malaria Pel-Ebstein Pattern → Lymphoma/Tuberculosis Pulse-Temp Dissociation → Typhoid/Brucellosis

19. Pattern of Fever

20. 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.

21. Physical Examination • Examine for Lymphadenopathy Cervical Area 1. Lymphoma (Localized) 2. Tuberculosis 3. Infectious Mononucleosis 4. Lymphadenitis (bacterial)

22. Diagnostic Testing • CBC with a differential WBC count and a urinalysis should be part of the initial laboratory evaluation. • An erythrocyte sedimentation rate (ESR). • C-reactive protein is another acute-phase reactant that becomes elevated and returns to normal more rapidly than the ESR.

23. Diagnostic Testing • serology • 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 Screening

24. Diagnostic Testing • Cultures • Blood • 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 Tuberculosis • Any normal sterile: • CSF/urine/pleural or peritoneal fluid • Bone marrow aspirate → Tuberculosis/Brucellosis • Lymph node Bx → TB

25. Diagnostic Testing • Imaging Studies: … to localize abnormalities for definite tests or treatment • Chest 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

26. 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

27. The majority of disease remaining after an initial NEGATIVE work-up are: • Neoplasm • Seronegative Collagen Vascular Disease • Increasing Tuberculosis • Increasing Drug Addition • Endocarditis • HIV with or without infection or malignancy • Implanted prosthetic devices • Travel … New Exposure

28. 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.

29. 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.

30. THANK YOU