FEVER AND FEVER OF UNKNOWN ORİGİN

1. FEVER AND FEVER OF UNKNOWN ORİGİN Meral Sonmezoglu, MD. Assoc Professor of Infectious Dıseases

2. BODY TEMPERATURE

3. BODY TEMPERATURE • Heat is derived from biochemical reactions occuring in all living cells (glucose catabolism, ATP) • Shivering is primary means of by which heat is enhanced • Heat is generated primarily in vital organs lying deep within the body core • Distributed thoughout the body via the circulatory system • Heat is lost from body surfaces to teh envirement

4. BODY TEMPERATURE • The mean oral temperature 36.8 ºC 0.4 ºC • Low level at 6 AM and high level at 4 to 6 PM, with normal daily variation is 0.5 ºC • Rectal temperature 0.4 ºC higher than oral • Unadjusted-mode TM temperature 0.8 ºC lower than rectal • Lower esophageal temperature closely reflect core temperature

5. NORMAL BODY TEMPERATURE • Maximum normal oral temperature At 6 AM : 37.2 At 4 PM : 37.7

7. DISCOMFORT DUE TO FEVER • For each 1 °C elevation of body temperature: • Metabolic rate increase 10-15% • Insensible water loss increase 300-500ml/m2/day • O2 consumption increase 13% • Heart rate increase 10-15/min

8. Combined symptoms Fever pattern Medication Surgical or dental procedure Any prosthetic materials or implanted devices Occupation ( animal; fume; infectious agent or infected individuals ) Travel history Unusual hobbies Dietary proclivities Household pets Sexual exposure IV drug abuse, alcoholism Trauma Animal or insect bite Blood transfusion immunization Family history APPROACH TO THE PATIENTHISTORY

9. APPROACH TO FEVER • Underlying Diseases: • Splenectomy • Surgical Implantation of Prosthesis • Immunodeficiency • Chronic Diseases: Cirrhosis Chronic Heart Diseases Chronic Lung Diseases

11. APPROACH TO THE PATIENT PHYSICAL EXAMINATION • Head to toe • Finger to hole • Special attention to skin, lymph nodes, eyes, nail bed, CV system, chest , abdomen, musculoskeletal system, and nerve system. • Rectal examination is imperative • Penis, scrotum, testes , foreskin and pelvic examination in women should be examined

12. APPROACH TO FEVER • Associated Symptoms: • Shaking chills • Ear pain,Ear drainage,Hearing loss • Visual and Eye Symptoms • Sore Throat • Chest and Pulmonary Symptoms • Abdominal Symptoms • Back pain, Joint or Skeletal pain

13. APPROACH TO THE PATIENT LABORATORY TESTS • Clinical Pathology • CBC+DC+PLT, blood smear, UA, ESR, abnormal fluid accumulation and CSF examination, bone mallow aspiration, stool routine • Chemistry • Electrolyte, BUN, creatinine, LFTs, amylase, CPK and serology… • Microbiology • Gram’s stain and culture • Imaging • Plain film, sonography, CT, MRI and Gallium scan

14. FEVER OF UNKNOWN ORIGIN

15. FEVER OF UNKNOWN ORIGIN DEFINITION • Defined by Petersdorf and Beeson in 1961 • Temperature > 38.3 ºC on several occasions • A duration of fever of > 3 weeks • Failure to reach a diagnosis despite 1 week of inpatient investigation • Durack and Street proposed a new system in 1991 • and suggested two changes to the earlier • definition. • Durrack and Street proposed four types of FUO

17. Classic FUO • Temperature > 38ºC (101ºF) recordedon several occasions occurring for more than three weeks • in spite of investigations on three OPD visits or threedays of stay in hospital or • one week of invasiveambulatory investigations is called classic FUO

18. Nosocomial FUO • Temperaturemorethan 38.3ºC (> 101°F) is recorded on several occasions in ahospitalized patient who is receiving acute care and inwhom infection was not manifest or incubating onadmission. • Three days ofinvestigations including at least two days incubation ofcultures, is the minimum requirement for this diagnosis

19. Neutropenic FUO • Temperature of > 38.3ºC (101ºF)on several ocasion is observed in a patient whoseneutrophil count is less than 500/microliter or is expectedto fall to that level in 1 or 2 days • This diagnosis should be considered wheninvestigation including at least two days of incubationof cultures. • It is also called immunodeficientFUO

20. HIV associated FUO • Temperature of > 38.3ºC (>101ºF) on several occasions is found over a period ofmore than 4 weeks for our patient or more than threedays for hospitalized patients with HIV infection • This diagnosis is considered ifappropriate investigations over three days including twoday of incubation of cultures reveals no source

21. FUO CAUSE • Big three • Infection (25-30%) • Malignancy (10-30%) • Collagen vascular disorder (10-15%) • Unknown (5-10%)

26. FEVER OF UNKNOWN ORIGIN: REPORT OF 27 CASES

27. A clinical review of 449 cases with fever of unknown origin • Out of the 449 FUO cases, definite diagnosis was eventually achieved in 387 patients (86.9%). • The most common causes of FUO were infectious diseases (56.8%), with tuberculosis accounting for 43.6% of cases of infection. • 76 patients were suffered from collagen vascular diseases (CVD): with Still's disease, systemic lupus erythematosus and vasculitis accounting for 34.2% (26/76), 18.4% (14/76) and 13.2% (10/76) of the this category, respectively. • 16.5% (64/449) of the FUO cases were diagnosed as malignancy. • Miscellaneous causes were found in 7.0% of the FUO cases. However, no definite diagnosis had been made in the remaining 62 (13.8%) cases until they discharged from the hospital

28. Fever of Unknown OriginPK Agarwal*, A Gogia**

29. Childhood World J Pediatr 2011;7(1):5-10

30. Infections in childhood World J Pediatr 2011;7(1):5-10

31. World J Pediatr 2011; 7(1):5-10

32. FUO MALIGNANCY ASSOCIATED • Hodgkin’s lymphoma • Non-Hodgkin lymphoma • Leukemia • Renal cell carcinoma • Hematoma • Colon carcinoma

33. FUO AUTOIMMUNE ASSOCIATED • SLE • RA • Adult Still’s disease • Temporal arteritis • Mixed connective tissue disease

34. FUO INFECTION ASSOCIATED • Intra-abdominal or pelvic abscess • Abscess 1/3 infection origin of FUO, most intra-abdominal or pelvic • Vague localized abdominal pain • Surgical complication or leakage of visceral contents • Liver abscess: elevated ALK-p K. pneumoniae bacteremia in DM, alcoholism, Liver cirrhosis Liver echo may be negative, so abdominal CT is important for diagnosis

35. FUO INFECTION ASSOCIATED • Osteomyelitis and septic hip • Tenderness over infected site, but some patients only with fever • Associated sign: L-spine OM with root compression sign, vertebral OM with psoas muscle abscess or CV surgery with sternal OM • Septic hip: 16% of septic arthritis, most with OA or destructive joint, so that with prolonged and insidious onset • Diagnostic tool: Bone scan or Gallium scan CT or MRI

36. FUO INFECTION ASSOCIATED • Infectious endocarditis • Clue of DX: continuous bacteremia, new murmurs, vascular phenomenon, vegetation on cardiac echo, and unexplained fever • Culture negative endocarditis Recently received antibiotics HACEK group organisms. Haemophilus parainfluenaze/ aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, andKingella kingae Fungus, Rickettsia and Chlamydia • TTE(60%) and TEE(95%)

37. FUO INFECTION ASSOCIATED • Granulomatous infection • TB( extrapulmonary TB or miliary TB) is the most common cause in Taiwan • TB may involve liver, spleen, bone, kidneys, pericardium or meninges and in miliary TB of lung CXR may be negative initial • Bone marrow study may diagnose • Nontuberculous mycobacterial infections and deep-seated fungal infection

38. FUO INFECTION ASSOCIATED • Dengue fever • Infectious mononucleosis • Scrub typhus • Typhoid fever • HIV • Malaria • Amebiasis • NG related sinusitis

40. Thank You