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FEVER AND FEVER OF UNKNOWN ORİGİN Meral Sonmezoglu, MD. Assoc Professor of Infectious Dıseases 2007 BODY TEMPERATURE 2007 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 2007 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 2007 NORMAL BODY TEMPERATURE Maximum normal oral temperature At 6 AM : 37.2 At 4 PM : 37.7 2007 2007 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 2007 APPROACH TO THE PATIENT HISTORY 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 2007 APPROACH TO FEVER Underlying Diseases: Splenectomy Surgical Implantation of Prosthesis Immunodeficiency Chronic Diseases: Cirrhosis Chronic Heart Diseases Chronic Lung Diseases 2007 2007 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 2007 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 2007 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 2007 FEVER OF UNKNOWN ORIGIN 2007 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 2007 Category of FUO Feature Nosocomial Patient’s situation Hospitalized, acute care, no Neutrophil count either infection when admitted <500 μL or expected to reach that level in 1-2 days b 3 days 3 daysb Duration of illness while under investigation Examples of cause Neutropenic HIV-Associated Classic Confirmed HIV-positive All others with fever for 3 weeks 3 daysb (or 4 weeks as out- 3 daysb or three outpatient patient) visits Septic thrombophlebitis, Perianal infection, aspergil- MAIc infection, tuberculosinusitis, Clostridium losis, candidemia sis, non-Hodgkin’s lymdifficile colitis, drug phoma, drug fever fever a All require temperatures for 38.3C on several occasions. b Includes at least 2 days’ incubation of microbiology cultures. c M. avium/M. intracellulare. Infections, malignancy, inflammatory diseases, drug fever 2007 Classic FUO • • • Temperature > 38ºC (101ºF) recorded on several occasions occurring for more than three weeks in spite of investigations on three OPD visits or three days of stay in hospital or one week of invasive ambulatory investigations is called classic FUO 2007 Nosocomial FUO • Temperature more than 38.3ºC (> 101°F) is recorded on several occasions in a hospitalized patient who is receiving acute care and in whom infection was not manifest or incubating on admission. • Three days of investigations including at least two days incubation of cultures, is the minimum requirement for this diagnosis 2007 Neutropenic FUO • Temperature of > 38.3ºC (101ºF) on several ocasion is observed in a patient whose neutrophil count is less than 500/microliter or is expected to fall to that level in 1 or 2 days • This diagnosis should be considered when investigation including at least two days of incubation of cultures. • It is also called immunodeficient FUO 2007 HIV associated FUO • Temperature of > 38.3ºC (>101ºF) on several occasions is found over a period of more than 4 weeks for our patient or more than three days for hospitalized patients with HIV infection • This diagnosis is considered if appropriate investigations over three days including two day of incubation of cultures reveals no source 2007 FUO CAUSE Big three Infection (25-30%) Malignancy (10-30%) Collagen vascular disorder (10-15%) Unknown (5-10%) 2007 2007 2007 2007 2007 FEVER OF UNKNOWN ORIGIN: REPORT OF 27 CASES 2007 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 2007 Fever of Unknown Origin PK Agarwal*, A Gogia** 2007 Childhood World J Pediatr 2011;7(1):5-10 2007 Infections in childhood World J Pediatr 2011;7(1):5-10 2007 World J Pediatr 2011; 7(1):5-10 2007 FUO MALIGNANCY ASSOCIATED Hodgkin’s lymphoma Non-Hodgkin lymphoma Leukemia Renal cell carcinoma Hematoma Colon carcinoma 2007 FUO AUTOIMMUNE ASSOCIATED SLE RA Adult Still’s disease Temporal arteritis Mixed connective tissue disease 2007 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 2007 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 2007 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, and Kingella kingae Fungus, Rickettsia and Chlamydia TTE(60%) and TEE(95%) 2007 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 2007 FUO INFECTION ASSOCIATED Dengue fever Infectious mononucleosis Scrub typhus Typhoid fever HIV Malaria Amebiasis NG related sinusitis 2007 2007 Thank You 2007