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

2. LEARNING OBJECTIVES 1- Define fever and FUO. 2- Put a differential diagnosis. 3- Master a panel of investigations. 4- Decide when to start empirical therapy?

3. MCQ The commonest cause of PUO is: A- A common disease presenting in an atypical way. B- A rare disease presenting in atypical way. C- A common disease presenting typically. D- A rare disease presenting typically.

4. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 1- How you define this complaint in view of duration? 2- Put a differential diagnosis inside a general frame? 3- What shall you ask in the context of history? 4- What are the general and special sites you look for in physical examination? 5- Set a panel of investigations you are planning to perform? 6- Start a treatment plan?

5. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 1- How you define this complaint in view of duration?

6. DEFINITIONS Fever: A rectal temperature of ≥38 C. It fluctuates in degree and timing. FWLS (Fever without localising sign): Fever of acute onset, with duration of <1 wk and without localizing signs. 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.

7. Axillary 36 - 37.4  C Oral 36.7 - 37.7  C Rectal 36.9 - 37.9  C Range of normal temperature

8. PATHOGENESIS Regulators: 1- Thermo sensitive neurons in pre-optic and anterior hypothalamus 2- Blood temperature 3- Receptors in skin and muscles Mechanisms: 1- Pyrogens (endogenous and exogenous) 2- Heat production exceeding loss 3- Defective Heat loss

9. Continuous: Temperature remains above normal throughout the day and does not fluctuate more than 1 °C in 24 hrs Typhoid, lobar pneumonia, Remittent: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours SBE Intermittent: The temperature elevation is present only for a certain period, later cycling back to normal Kala Azar Undulant: fever is typically undulant, rising and falling like a wave Brucellosis Relapsing: multiple episodes of fever occur and each may last up to 3 days. Individuals may be free of fever for up to 2 weeks before it returns. Tick borne

10. Remember the sequelae FeverBacteremiaSepticemiaSepsis Septic shock MODDeath SIR

11. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 2- Put a differential diagnosis inside a general frame?

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

13. 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

14. 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

15. Always look for Abscesses: Abdominal, brain, dental, hepatic, pelvic, perinephric, rectal, subphrenic, psoas CAUSES

16. APPROACH The Best Approach “there is no substitute for observing the patient, talking to him and thinking about him”

17. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 3- What shall you ask in the context of history?

18. 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.

19. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 4- What are the general and special sites you look for in physical examination?

20. 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.

21. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 5- Set a panel of investigations you are planning to perform?

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

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

24. INVESTIGATIONS Level 3: Tissue biopsy, Endoscopy

25. INVESTIGATIONS avoid indiscriminately ordering a large battery of tests.avoid indiscriminately ordering a large battery of tests.

26. A 10 - year old female, presented to the outpatient clinic with a 4 - week history of fever (38.3 C – 39.5 C) and easy fatigability. She underwent a good primary work up by the family physician prior to referral with failure to reach a diagnosis. She is sitting now with her worried parents in the desk next to you and ready to receive your questions and actions. 6- Start a treatment plan?

27. Treatment in general, NONE Until diagnosis

28. Treatment You should know that 1. most children will get better 2. most children have common illnesses 3. it hasn’t killed them yet! So do not rush to antibiotic treatment.

29. Treatment Admit 1- Reliability 2- Toxicity 3- Invasive investigations

30. Treatment (little or no role in cases of classic fever of unknown origin) Empirical therapy (little or no role in cases of classic fever of unknown origin) is indicated only in: 1- Nonsteroidal agents in presumed JIA 2- Antituberculosis drugs in critically ill children with possible disseminated TB 3- Clinically deteriorating with suspicion of bacteremia or sepsis. 4- Immunocompromised Antibiotics if used should be at targeted disease rather than blanket therapy with 4-5 antibiotics.

31. FUO is more likely to be an unusual presentation of a common disorder than a common presentation of a rare disorder. FUO is more likely to be an unusual presentation of a common disorder than a common presentation of a rare disorder. Giving antibiotics to a child with FUO is like shooting a gun into dark room Giving antibiotics to a child with FUO is like shooting a gun into dark room Take home message

32. SUMMARY OF DEFINITIONS FEATURECLASSIC FUO Definition>38.0°C, >3 wk, >2 visits or 1 wk in hospital Patient locationCommunity, clinic, or hospital Leading causesinfections, inflammatory conditions, Cancer, undiagnosed, habitual hyperthermia History emphasis Travel, contacts, animal and insect exposure, medications, immunizations, family history, cardiac valve disorder Examination emphasis Fundi, oropharynx, temporal artery, abdomen, lymph nodes, spleen, joints, skin, nails, genitalia, rectum or prostate, lower limb deep veins Investigation emphasisImaging, biopsies, sedimentation rate, skin tests Management Observation, outpatient temperature chart, investigations, avoidance of empirical drug treatments Time course of diseaseMonths Tempo of investigationWeeks

33. Infections Oncology Rheumatology

34. Thank you