Pyrexia of unknown origin edited
- 1. An Update on ‘Pyrexia of Unknown Origin’ Speaker Dr. AL TARIQUE Registrar- Medicine
- 2. Pyrexia of Unknown Origin • A temperature above 38°C on multiple occasions for more than 3 weeks, without diagnosis, despite initial investigation in hospital for 1 week. • The definition has been relaxed to allow for investigation over 3 days of inpatient care, three outpatient visits or 1 week of intensive ambulatory investigation.
- 3. Aetiology Infections, 30% Malignancy, 20% Connective tissue disorders, 15% Miscellaneous, 20% Idiopathic, 15%
- 4. Specific locations Abscesses: Hepatobiliary diverticular urinary tract (including prostate) pulmonary CNS Infections (~30%)
- 5. Infections of oral cavity, head and neck Infective endocarditis Bone and joint infections
- 6. Specific organisms Tuberculosis HIV-1 infection Other viral infection Cytomegalovirus (CMV), Epstein–Barr virus (EBV)
- 7. Fungal infections Aspergillus spp. Candida spp. or dimorphic fungi Infections with fastidious organisms Bartonella spp. Tropheryma whipplei
- 8. Specific patient groups Recently spent time in a region with geographically restricted infection • Malaria • Dengue • Rickettsial infections • Brucella spp.
- 9. • Amoebic liver abscess • Enteric fever • Leishmania spp. • Middle east respiratory syndrome coronavirus
- 10. Residence in or travel to region with endemic infection • TB • Extensively drug resistant TB • Brucella spp. • HIV 1 • Trypanosoma cruzi
- 11. • Infections related to prosthetic materials and surgical procedures • Pneumonia • Urinary tract infection • Central venous catheter infections Nosocomial infections
- 12. HIV-positive individuals • Acute retroviral syndrome • AIDS-defining infections Disseminated Mycobacterium avium complex, Pneumocystis carinii, CMV and others
- 13. Malignancy (~20%) Haematological malignancy Lymphoma Leukaemia Solid tumours Renal cell carcinoma Hepatocellular carcinoma Carcinoma of colon Gastric carcinoma
- 14. Connective tissue disorders (~15%) Older adults Temporal arteritis/Polymyalgia rheumatica Younger adults Still’s disease (juvenile rheumatoid arthritis) Systemic lupus erythematosus (SLE) Vasculitic disorders Polymyositis Rheumatic fever
- 15. Miscellaneous (~20%) Cardiovascular Atrial myxoma Aortitis Aortic dissection Respiratory Sarcoidosis Pulmonary embolism Extrinsic allergic alveolitis
- 16. Gastrointestinal Inflammatory bowel disease Alcoholic liver disease Pancreatitis Endocrine/metabolic Thyrotoxicosis Thyroiditis Phaeochromocytoma
- 17. Haematological Haemolytic anaemia Thrombotic thrombocytopenic purpura Myeloproliferative disorders Inherited Familial Mediterranean fever Periodic fever syndromes
- 18. Drug reactions / Drug induced fever Allopurinol, Carbamazepine, Lamotrigine, Phenytoin, Sulfasalazine, Frusemide Antimicrobials Sulfonamides, Minocycline, Vancomycin, β-lactam antibiotics and isoniazid. Cardiovascular drug : Quinidine Factitious fever
- 19. Structured Approach Pyrexia of unknown origin
- 20. Fever > 38°C (100.4°F) and illness lasting > 3 weeks, without diagnosis, despite initial investigation during 3 days of inpatient care or after more than three outpatient visits. History and physical examination Stop antibiotic treatment and glucocorticoids
- 21. Obligatory investigations: ESR & CRP, Hemoglobin, Platelet Count, Leukocyte Count&Differential, Electrolytes & Creatinine, Total Protein, Protein Electrophoresis, Alkaline Phosphatase, ALT, AST, LDH, Creatine Kinase, Antinuclear Antibodies, Rheumatoid Factor, Urinalysis, Blood Cultures, Urine Culture, Chest X-ray, Abdominal Ultrasonography, Tuberculin Skin Test
- 22. Exclude manipulation with thermometer Stop or replace medication to exclude drug fever PDCs present PDCs absent or misleading
- 23. PDCs present PDCs absent or misleading Guided diagnostic tests Cryoglobulin & fundoscopy NO DIAGNOSISDIAGNOSIS FDG-PET/CT (or labeled leukocyte scintigraphy or gallium scan)
- 24. Scintigraphy abnormal Scintigraphy normal Confirmation of abnormality (e.g. biopsy, culture) • Repeat history & physical examination • Perform PDC-driven invasive testing NO DIAGNOSISDIAGNOSIS DIAGNOSIS NO DIAGNOSIS
- 25. Stable condition: Follow-up for new PDCs Consider NSAID Deterioration : Further diagnostic tests Consider therapeutic trial Chest and abdominal CT Temporal artery biopsy (>55years) NO DIAGNOSISDIAGNOSIS
- 26. Potentially diagnostic clues (PDCs) • The most important step in the diagnostic workup is the search for potentially diagnostic clues (PDCs) through complete and repeated history taking and physical examination and the obligatory investigations.
- 27. • PDCs are defined as all localizing signs, symptoms, and abnormalities potentially pointing toward a diagnosis.
- 28. Pyrexia of unknown origin A Clinical Approach
- 29. History taking History of presenting complaint- 1. Onset : Acute : Malaria, Pyogenic infection Gradual : TB, Typhoid fever 2. Character High grade fever : UTI, Malaria Low grade fever : TB
- 30. 3.Pattern: Despite historical claims, pattern of fever are not especially helpful in establishing a specific diagnosis. • Continued fever: Fluctuation of fever not >1°C ,does not touch baseline. • Intermittent fever: Fever that persist for several hours ,always touches baseline • Remittent fever: Fever fluctuates > 2°C , does not touch the baseline.
- 31. 4.Associated symptoms • Chills and rigors : acute pyelonephritis, acute cholangitis, subphrenic abscess, pyogenic lung abscess, SBE, lobar pneumonia • Night sweats : TB, infective endocarditis • Loss of weight : Malignancy, Vasculitis, TB, HIV, IBD, thyrotoxicosis
- 32. Cough : TB, PE, Q fever, sarcoidosis, legionnaire’s disease. Nasal symptoms : sinusitis, GPA, relapsing fever, psittacosis Confusion : TB, Cryptococcus, Sarcoid, enteric fever. Arthralgia : SLE, infective endocarditis, Lyme disease, brucellosis, enteric fever.
- 33. 5. Antecedents -prior to onset of fever: Dental extraction – infective endocarditis Urinary catherization – UTI, bacteremia
- 34. History of past illness • Past history of infection . e.g. malaria, kala-azar, tuberculosis. • History of recent dental procedure. • History of surgery and trauma. • History of neoplasia, connective tissue disorders, prosthetic valve, liver disorder.
- 35. Sexual history • HIV 1 transmission Family history • TB, familial Mediterranean fever. History of Intravenous drug injection or receipt of blood products • HIV -1, HBV and HCV
- 36. Travel history • Amoebiasis, typhoid fever, malaria, schistosomiasis Occupation • E.g. anthrax in leather tannery workers History of Animal exposures • Brucellosis, Toxoplasmosis, Leptospirosis, Q fever, Psittacosis Diet history • Consider undercooked meats , shellfish, unpasteurized dairy products or well water
- 37. Pyrexia of unknown origin Physical examination
- 38. Observations • Temperature • Sweating • Weight loss • Respiratory distress • Pallor • Jaundice • Altered consciousness
- 39. Skin • Generalised erythema • Rash-HIV, EBV, SLE, Vasculitis, still’s disease, endocarditis • IV injection track marks • Surgical scars • Prosthetic devices, e.g. central venous catheters • Tattoos
- 40. Hands and nails • Signs of chronic liver disease • Splinter hemorrhages • Finger Clubbing • Janeway lesions • Vasculitis lesions
- 41. Oropharynx • Dental caries • Tonsillar enlargement or exudate • Candidiasis
- 42. Eyes • Conjunctivitis –leptospirosis, relapsing fever, spotted fever, trichinosis • Uveitis- TB, sarcoid, adult Still’s disease, SLE, Behcet’s disease • Roth’s spot in infective endocarditis • Hemorrhages & exudates – cytomegalovirus retinitis • Choroidal lesions of tuberculosis
- 43. Head and neck • Lymphadenopathy- Lymphoma, TB, EBV, CMV, HIV, Toxoplasmosis • Parotidomegaly
- 44. Neurological • Neck stiffness • Photophobia • Delirium • Focal neurological signs
- 45. Abdomen • Hepatomegaly- TB, EBV, malignancy, malaria, enteric fever, granulomatous hepatitis, visceral leishmaniasis • Splenomegaly – Leukaemia, Lymphoma, TB, IE, CMV, EBV, sarcoid, enteric fever • Renal – Chronic pyelonephritis, perinephric abscess, renal tumor • Mass lesions • Surgical drains
- 46. Heart and Lungs • Tachycardia, hypotension • Murmurs or prosthetic heart sounds • Pericardial rub • Signs of consolidations • Pleural or pericardial effusions
- 47. Musculoskeletal • Joint swelling, erythema or tenderness • Localised tender spine suggestive of epidural abscesses or discitis • Draining sinus of chronic osteomyelitis
- 48. Genitalia and rectum • Epididymo-orchitis • Ulceration and discharge • Testicular swelling or nodules • Inguinal lymphadenopathy • Prostatic tenderness
- 49. Treatment Supportive treatment • Paracetamol • Tepid sponging • Replacement of salt and water is important in patients with drenching sweats. According to cause
- 50. Prognosis • The overall mortality is 30-40%, mainly attributable to malignancy in older patients. • If no cause is found, the long term mortality is low and fever often settles spontaneously.
- 51. Home massage • PUO is far more often caused by an atypical presentation of a rather common disease than by a very rare disease. • Because of unavailability of all diagnostic facilities and the poverty of general population, PUO can not be evaluated in every case
- 52. • The most likely cause of PUO, like all other countries of the world, is infection in our country. • Studies support that 50% of cases are caused by infections, eg, tuberculosis in western nations.
- 53. • As the duration of fever increases, the likelihood of an infectious cause decreases. • Empirical therapeutic trials with antibiotics, glucocorticoids, or antituberculous agents should be avoided in PUO except when a patient’s condition is rapidly deteriorating.
- 54. THANK YOU