Fever unknown Origin

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Fever Unknown Origin a challenge for physician

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Fever unknown Origin

  1. 1. Fever Unknown Origin Diagnosis and Management Budi Riyanto
  2. 2. “ Humanity has but three great enemies; Fever, Famine and War. Of these by far the most terrible , is fever.” ( Sir William Osler, Father of Modern medicine)
  3. 3. Budi Riyanto JADE 2014 3
  4. 4. • Fever is an common feature of many illness. In majority cases the diagnosis is diagnosed or fever disappears spontaneous. • When fever persist and underlying diagnosis is not obvious, it presents a challenge for patient and physician FEVER Budi Riyanto JADE 2014
  5. 5. FEVER .. ?? • All the human being must have been expérience with Fever • Fever : Normal / Physiologic, but also is can sign of pathologic process / worst sign • But … some people always think the fever must be resolve in short time and a “simple / easy problems” Budi Riyanto JADE 2014
  6. 6. Fever • Fever: Abnormal increase in body temperature, oral -more than 37.6 °C (100.4 °F) Rectal – more than 38 °C (101 °F) • Homeostatic mechanism : fluctuation of ±1 to 1.5 °C Budi Riyanto JADE 2014
  7. 7. FEVER UNKNOWN ORIGIN Budi Riyanto JADE 2014 7
  8. 8. Original Definition (by Petersdorf and Beeson, 1961) • Temperatures ≥ 38.3ºC (101ºF) on several occasions • Fever ≥ 3 weeks • Failure to reach a diagnosis despite 1 week of inpatient investigations or 3 outpatient visits [1 IP / 3 OP] Budi Riyanto JADE 2014 8
  9. 9. Cases illustration • A 50 year old man was admitted with fever of three weeks duration. – On examination there was hepatosplenomegaly. – Routine urine and blood examinations were normal. – Widal test and Mantoux test were negative. Chest X-Ray and HIV were negative. Budi Riyanto JADE 2014 9
  10. 10. • A 49 year old man came to hospital with : – Pain in the right loin and fever of one month duration. – Loss of appetite and loss of weight were present. – He was investigated for UTI. – Repeated URE and urine cultures were negative. – Renal angle was dull but non tender. – CT scan of abdomen was diagnostic Budi Riyanto JADE 2014 10 Cases illustration
  11. 11. Classification of FUO Category Definition Aetiologies Classic • Temperature >38.3°C (100.9°F) ; • Duration of >3 weeks • Evaluation of at least 3 outpatient visits or 3 days in hospital • Infection • Malignancy • collagen vascular disease Nosocomial • Temperature >38.3°C • Patient hospitalized ≥ 24 hours but no fever or incubating on admission • Evaluation of at least 3 days • Clostridium difficile enterocolitis • drug-induced • pulmonary embolism • septic thrombophlebitis, • sinusitis Immune deficient (neutropenic) • Temperature >38.3°C • Neutrophil count ≤ 500 per mm3 • Evaluation of at least 3 days • Opportunistic bacterial infections, • aspergillosis, • candidiasis, • herpes virus HIV- associated • Temperature >38.3°C • Duration of >4 weeks for outpatients, >3 days for inpatients • HIV infection confirmed • Cytomegalovirus, • Mycobacterium avium-intracellulare complex, • Pneumocystis carinii pneumonia, • drug-induced, • Kaposi’s sarcoma, lymphoma Budi Riyanto JADE 2014 11
  12. 12. Frequency base on etiology FUO Infection (40%) Malignancy (25%) Autoimmune Disease (15%) Others/ Miscellaneous (10%) Undiagnosed (10%) Budi Riyanto JADE 2014 12
  13. 13. Infections • Bacterial: abscesses, TB, complicated UTI, endocarditis, osteomyelitis, sinusitis, Lyme disease, prostatitis, cholecystitis, empyema, biliary tract infection, brucellosis, typhoid, leptospirosis, Q fever, borreliosis, etc. • Parasite: Malaria, toxoplasmosis, leishmaniasis, etc. • Fungal: histoplasmosis, etc. • Viral: CMV, infectious mononucleosis, HIV, etc. Budi Riyanto JADE 2014 13
  14. 14. Malignancies • Haematological – Lymphoma – Chronic leukaemia • Non-haematological – Renal cell cancer – Hepatocellular carcinoma – Pancreatic cancer – Colon cancer – Hepatoma – Myelodysplastic Syndrome – Sarcomas Budi Riyanto JADE 2014 14
  15. 15. Others/miscellaneous • Drugs: penicillin, phenytoin, captopril, allopurinol, erythromycin, cimetidine, etc. • Hyperthyroidism • Alcoholic hepatitis • Sarcoidosis • Inflammatory bowel disease • Deep Venous Thrombosis Budi Riyanto JADE 2014 15
  16. 16. NOSOCOMIAL FUO • After 3 days of hospitalization • Risk factors encountered in hospital – Surgical procedure – Urinary and respiratory instrumentation – IVFD / devices – Transfusion related viral infections – Drug therapy – Post Myocardial infarction syndrome – Pulmonary thromboembolism – Immobilisation Budi Riyanto JADE 2014 16
  17. 17. Nosocomial FUO • More than 50% of patients with nosocomial PUO are due to infection. • Focus on sites where occult infections may be sequestered, such as: - Sinusitis of patients with NG or orotracheal tubes. - Prostatic abscess in a man with a urinary catheter. • 25% of non-infectious cause includes: - Acalculous cholecystitis, - Deep vein thrombophlebitis - Pulmonary embolism. Budi Riyanto JADE 2014 17
  18. 18. Roth AR and Basello GM. Am Fam Physician. 2003 Dec 1;68(11):2223-8. Budi Riyanto JADE 2014 18
  19. 19. HIV-associated PUO • HIV infection alone may be a cause of fever. • Common secondary causes include: - Tuberculosis - Toxoplasmosis - CMV infection - P. carinii infection - Salmonellosis - Cryptococcosis - Histoplasmosis - Non-Hodgkin's lymphoma - Drug-induced fever Budi Riyanto JADE 2014 19
  20. 20. DIAGNOSIS Budi Riyanto JADE 2014 20
  21. 21. Approach to patient with FUO • Stage 1: Careful history taking, physical examination and screening tests • Stage 2: Review the history, repeating physical examination • Stage 3: Specific diagnostic tests & noninvasive investigations • Stage 4: Invasive tests Budi Riyanto JADE 2014
  22. 22. Budi Riyanto JADE 2014 22 Diagnosis Hx taking P.E Lab/Imaging
  23. 23. 1st • History taking “Fever” • Occupation • Exposure to animals • Travel history • Family history Budi Riyanto JADE 2014
  24. 24. Budi Riyanto JADE 2014 24 History Taking of Fever Fever • Onset • Character • Pattern Fever • Antecedent • Associated symptoms Fever • Past medical history • Past surgical history • Social history
  25. 25. Onset • Acute • Gradual Malaria , pyogenic infection TB, typhoid Character High Malaria , UTI ,TB, drug Pattern • Sustainable/persistent • Intermittent • Relapsing Typhoid, drug Daily (abscess),twice daily( leishmaniasis),saddle back (dengue . leptospira, borellia) Malaria ,lymphoma Antecedent Prior onset the fever Dental extraction (endocarditis),urinary catheterization (UTI, bacteremia) Associated symptoms • Chills, • Night sweat, • Loss weight, • Dyspnea, • Headache, • Joint pain Budi Riyanto JADE 2014 25 Type of fever and diseases
  26. 26.  Travel  amoebiasis, typhoid fever, malaria, Schistosomiasis  Residential area  malaria, leptospirosis, brucellosis  Occupation  farmers, veterinarian, slaughter-house workers = Brucellosis  workers in the plastic industries = polymer-fume fever  Contact with domestic / wild animal / birds :  Brucellosis, psittacosis (pigeons), Leptospirosis, Q fever, Toxoplasmosis  Diet history  unpasteurized milk/cheese = Brucellosis  poorly cooked pork = Trichinosis  IVDU = HIV-AIDS related condition, endocarditis  Sexual orientation = HIV, STD, PID  Close contact with TB patients Social history and risk of infection Budi Riyanto JADE 2014 26
  27. 27.  Past Medical History  Malignancy = leukemia, lymphoma, hepatocellular carcinoma  HIV infection  DM  IBD  collagen vascular disease-SLE, RA, giant cell arteritis  TB  Heart disease: valvular heart disease  Past Surgical History  Post splenectomy/ post- transplantation  Prosthetic heart valve  Catheter, AV fistula  Recent surgery/ operation Medical history Budi Riyanto JADE 2014 27
  28. 28. Physical Examination Budi Riyanto JADE 2014 28 Hand Arm Head and Neck Face and mouth Chest Abdomen CNS
  29. 29. Body site Physical finding diagnosis Head Sinus tenderness sinusitis Temporal artery nodules & reduced pulsation Temporal arteritis oropharynx ulceration Disseminated Histoplasmosis Tender tooth Periapical abscess Fundi / conjunctiva Choroid tubercle Disseminated granulomatosis Petechiae, Roth’s spots Infective endocarditis Thyroid thyroid enlargement Thyroididtis Physical examination: Budi Riyanto JADE 2014 29
  30. 30. Body site Physical finding Diagnoses Heart murmur myxomas, endocarditis Abdomen Enlarged iliac crest lymph nodes , spleenomegaly lymphomas., disseminated granulomatosis Rectum Perirectal fluctuance and tenderness Abcess Prostatic tenderness Abcess Lower limbs deep vein tenderness DVT & thrombophlebitis Skin & nail Petechiae, splinter hemorrhages, subcutaneous nodules, clubbing Vasculitis, endocarditis Budi Riyanto JADE 2014 30
  31. 31. Contribution to diagnosis ID n (%) CVD+MD n(%) ND n(%) UD n(%) total History 14 (53.8) 31 (77.5)* 6(43) 0 51 Physical Examination 11 (42.3) 23(57.5) 5(35.7) 0 39 Biochemical test 7(27)* 23(57.5) 8(57.1) 0 38 Budi Riyanto JADE 2014 31 CONSTRIBUTION BASELINE FINDING Bilgul Mete,Int. J. Med. Sci. 2012, 9 Note : ID : Infectious Diseases,CVD:Collagen Vascular Diseases, MD : Miscellaneous diseases,UD : Undiagnosed * p< 0,001 when compared to other groups
  32. 32. Laboratory studies & investigation in FUO If any abnormality or clue is noted , further investigation is indicated Abdurachman K, Nurhan E , Sibel YK : Expert Rev Anti Infect Ther,2013,11(8) CBC with diff count Blood cultures Urine cultures Routine blood liver enzymes and bilirubin ESR CRP Hepatitis serology (if liver enzymes are abnormal) Urine analysis Chest radiograph
  33. 33. Free Powerpoint Templates Page 33 1. Echocardiography 2. Further X ray / abdomen exam including scan – IBD, abscesses, local sepsis) 3. Barium studies 4. IVU 5. Liver biopsy Further investigations 6. Exploratory laparotomy 7. Bronchoscopy Budi Riyanto JADE 2014
  34. 34. Chest X ray and CT scan • CT scan provides spatial resolution • Detect small nodules • Hilar / mediastinal adenopathy ( lymphoma, sarcoidosis),can be revealed • Chest CT very useful in FUO • Chest CT (from data) : – Can detect pulmonary TB 91% – Multi center study : specificity 77%,sensitivity 82% Budi Riyanto JADE 2014
  35. 35. Contribution of imaging to diagnosis FUO Contribution to diagnosis ID CVD+ MD ND UD N/(%) All imaging studies 21* 17 9 (-) 47(47) Abdominal USG (n:48) 4 3 1 (-) 8(16.6) Chest X-ray (n:96) 8** 3 0 0 11(11.4) Thorax CT (n:86) 13 11 2 (-) 26(30.2) Abdominal CT (n:80) 7 6 3 (-) 16(20) Bilgul Mete, Int. J. Med. Sci. 2012, 9 * p<0.001 when compared to other groups ** p= 0.001 when compared with other groups
  36. 36. Role and Interpretation of Fluorodeoxyglucose- Positron Emission Tomography/Computed Tomography in HIV-Infected Patients With Fever of Unknown Origin (A Prospective Study) • Objective : study was to evaluate prospectively the usefulness of fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG- PET /CT ) in investigation of fever of unknown origin (FUO) in HIV- positive patient ‘s • Results : FDG-PET /CT contributed to the diagnosis or exclusion of a focal aetiology of the febrile stat e in 80% of patients with FUO. The presence of increased FDG uptake in the central lymph node has 100% specificity for focal aetiology of fever. Budi Riyanto JADE 2014 36 Martin C, Castaigne.C , Tondeur M : HIV Medicine.2013;14(8):455-462.
  37. 37. Diagnostic role of imaging and invasive procedure Sensitivity Specificity NPV PPV Thorax CT 100 65 100 55 Abdominal USG 100 67 100 30 Abdominal CT 100 44 100 31 Biopsies 85 100 85 100 Budi Riyanto JADE 2014 37 Bilgul Mete, Int. J. Med. Sci. 2012, 9
  38. 38. If failed… • Review history & repeat physical examination !! • Specific investigations ( not all ..) • Repeat sampling of blood & other body fluids. • Skin tests • Blood for antibodies – HIV antibodies, CMV antibodies, EBV antibodies. Budi Riyanto JADE 2014
  39. 39. MANAGEMENT  Therapy withheld until cause is found  Empirical corticosteroids or anti inflammatories in temporal arteritis.  Change of IV lines, catheters Budi Riyanto JADE 2014
  40. 40. 40 Hx/PE (+) finding Yes Order appropriate /spec Dx test NO CBC,electrolyte,LFT, culture,urine,ESR,PPD, Chest Ro Positive finding yes Order specific Dx test and follow up No CT scan Abd Infection malignancies autoimmune miscellaneus
  41. 41. Budi Riyanto JADE 2014 41 FUO Hx,PE, Lab/Investigation Unstable patients Signs specific diseases Immediate Dx test and initial empirical or specific therapy Stable patients Screening lab test Specific lab or imaging test Specific dx, spec treatment Repeated hx or exam,observe and antipyretic
  42. 42. FUO in HIV cases Budi Riyanto JADE 2014 42
  43. 43. Budi Riyanto JADE 2014 43
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  45. 45. PROGNOSIS • Poorest prognosis - elderly & malignant • Delay in diagnosis affects prognosis of intraabdominal infections, miliary tuberculosis, disseminated fungal infections & recurrent pulmonary emboli • Undiagnosed PUO for prolonged duration – good prognosis.
  46. 46. Sit with the patient and spend more time to take history Take history from the patient and not the bystanders Make a thorough and complete physical examination Make sure you examine the fundus of the eye Do appropriate investigations, but not total screening Order relevant investigations without hesitation Budi Riyanto JADE 2014 46
  47. 47. Budi Riyanto JADE 2014 47
  48. 48. Budi Riyanto JADE 2014 48

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