1. University Of Baghdad College of Medicine Dept. Of Pediatrics 5th Year Infectious Diseases Module

2. LEARNING OBJECTIVES 1- Be able to understand the main clinical presentations of PUO 2- Be able to formulate a differential and provisional diagnoses. 3- Plan a panel of investigations according to the suspected diagnosis. 4- Decide the plan of treatment.

3. DEFINITION FUO (Fever of unknown origin): Fever documented by a health care provider and for which the cause could not be identified after 3 wk of evaluation as an outpatient or after 1 wk of evaluation in the hospital.

4. between 5 and 15% of FUO cases defy diagnosis, despite exhaustive studies.

5. CAUSES 1- Infections: Bacterial Systemic: Brucellosis, Salmonella, Tuberculosis Localized infections: Osteomyelitis, Pneumonia and Sinusitis Viruses: CMV, Hepatitis viruses,HIV, IM (Epstein-Barr virus) Parasitic Diseases: Malaria,Toxoplasmosis Fungal diseases

6. CAUSES 2- Rheumatologic diseases JRA, Rheumatic fever, SLE and drug fever. 3- Neoplasms Leukemia, Lymphoma, other malignancies. 4- Miscellaneous Familial Mediterranean fever, Kawasaki disease. 5- Undiagnosed

7. HISTORY Fever specifications, sweating, antipyretics use and response, appearance, other complaints (CNS, urinary,,,,), pain (severity, site), rash and distribution, arthralgia / arthritis, travel, contact, animals, medications, hospitalization, immunizations, ethnicity, exposure to contaminated food or water.

8. CAREFUL PHYSICAL EXAMINATION General appearance and vital signs (heart rate, pressure, respiratory, temperature), pallor, jaundice, clubbing, skin and scalp, eyes, sinuses, oropharynx, LN, abdomen, musculoskeletal, genitourinary.

9. INVESTIGATIONS Level 1: CBC differentials, ESR, CRP, metabolic panel (RFT, LFT, elects), GUE, stool, C/S, LP, CXR, US, TB, EBV, CMV, cultures.

10. INVESTIGATIONS Level 2: Echo, CT, Bone scan, Serology, Autoimmune, Bone marrow

11. INVESTIGATIONS Level 3: Tissue biopsy, Endoscopy

12. Treatment in general, NONE Until diagnosis

13. Infections Oncology Rheumatology

14. Hints As the duration of fever increases, infectious etiology decreases Malignancy and factitious fever should be considered with more prolonged fever The most critical features of the evaluation of a patient with FUO is to take a carefully history and to reassess the patient frequently. The Best Approach is “there is no substitute for observing the patient, talking to him and thinking about him”

15. Hints It is important to look for uncommon presentation of common disease and to perform a detailed physical examination Clinically challenging - get expert help! Clinical balance between trial antimicrobial (often anti tuberculosis regimen) or corticosteroid trial. avoid indiscriminately ordering a large battery of tests.

17. Approach

18. Complete history and physical examination Positive findings: Order appropriate and specific diagnostic tests Negative findings CBC, ESR, LFT, GUE, Culture, Blood culture, Skin PPD, CXR, US, Muscle enzymes,,, Positive: Order appropriate and specific diagnostic tests and manage accordingly Negative results CT chest, abdomen and pelvis with contrast

19. Assign to most likely diagnosis Infection Autoimmune disease Urine, sputum culture, AFB, HIV, CMV, EBV serology, LP, Echo BMA, BMA, LN biopsy, Liver biopsy, colonoscopy Malignancy ASO, RF, ANA, muscle biopsy, skin biopsy

20. After full work up for PUO Empirical therapy Diagnosis Anti Tb, Antimicrobial, NSAID Watchful waiting No diagnosis Treatment

21. Task 1- Intra abdominal abscess History: Seven-year old male, PUO, Swinging in nature, with non specific localizing abdominal pain and a prior history of appendicitis. Physical examination: Febrile, Right iliac fossa mass Order relevant investigations and outline treatment accordingly.

22. Task 2- Pulmonary tuberculosis History: Eleven-year old male, PUO, cough, Weight loss, father have chronic undiagnosed cough. Physical examination: Febrile, cachectic, no LAP, bronchial breathing in the right upper zone. Order relevant investigations and outline treatment accordingly.

23. Task 3- Bacterial endocarditis History: Three-year old boy, PUO, known case of congenital heart disease (Ventricular septal defect), Physical examination: Febrile and heart murmur. Order relevant investigations and outline treatment accordingly.

24. Task 4- Urinary tract infection History: Seven-month old female, recurrent fever and diarrhea, failure to thrive, repeated episodes of vomiting Physical examination: Febrile, wasted, Order relevant investigations and outline treatment accordingly.

25. Task 5- Osteomyelitis History: Three-year old female, PUO, limping, tenderness in the right lower thigh. Physical examination: Febrile, toxic, swelling and tenderness in the lower right thigh. Order relevant investigations and outline treatment accordingly.

26. Task 6- Brucellosis History: Ten-year old girl, PUO, drenching sweating, history of ingestion of diary product, back pain Physical examination: Febrile, sweating Order relevant investigations and outline treatment accordingly.

27. Task 7- Kala-azar History: Three-year old female, from Diyala, PUO, abdominal distension, poor appetite. Physical examination: Febrile, organomegaly Order relevant investigations and outline treatment accordingly.

28. Task 8- Mononucleosis History: Nine-year old girl, PUO, bilateral cervical swelling, sore throat. Physical examination: Febrile, cervical LAP, exudative tonsillitis. Order relevant investigations and outline treatment accordingly.

29. Task 9- HIV History: Four-year old girl, recurrent fever, recurrent infections, skin rash (ecchymoses), mother is on regular blood transfusion Physical examination: Febrile, pneumonia, organomegaly, wasted Order relevant investigations and outline treatment accordingly.

30. Task 10- Leukemia History: Four-year old girl, PUO, abdominal distension, cervical swelling, skin rash (ecchymosis) Physical examination: Febrile, pallor, generalized LAP, petachial rash and ecchymoses, hepatosplenomegaly. Order relevant investigations and outline treatment accordingly.

31. Task 11- Lymphoma History: Four-year old girl, PUO, weight loss, sweating and abdominal distension Physical examination: Fever, pallor, abdominal mass Order relevant investigations and outline treatment accordingly.

32. Task 12- Juvenile Rheumatoid Arthritis History: Thirteen-year old girl, PUO, small joints swellings, skin rash. Physical examination: Febrile, joint swellings, maculopapular skin rash Order relevant investigations and outline treatment accordingly.

33. Task 13- Drug fever History: Four-year old girl, recurrent fever, case of undiagnosed fever on multiple drugs intake Physical examination: Febrile, Order relevant investigations and outline treatment accordingly.

34. Task 14- Factitious fever History: Five-year old girl, fever, non plausible manifestations, after a period of legitimate disorder, mother is a medical staff. Physical examination: Febrile. Order relevant investigations and outline treatment accordingly.

35. Task 15- Toxoplasmosis History: Seven-year old male, PUO, low grade with painless cervical swelling. History of raising pets at home. Physical examination: Febrile, unilateral cervical LAP. Order relevant investigations and outline treatment accordingly.

36. Thank you