Pyrexia of unknown origin
- 2. Fever of at least 101°F (38.3°C) that lasts for more than Three weeks OR occurs frequently without explanation. Even after Physician efforts to find the cause. Pyrexia of unknown origin is more often caused by an Atypical presentation of a Common entity than by a rare disorder.
- 3. Infections (30-40%)= Tuberculosis, mononucleosis, Lyme disease, cat scratch fever, endocarditis, and others Neoplasms (20-30%)=lymphoma, leukemia, pancreatic carcinoma, and other cancers and sarcomas. Collagen vascular diseases (10-20%) =Lupus, Rheumatoid arthritis, Inflammatory bowel disease, and others Miscellaneous diseases (15-20%)= Drug induced, Hyperthyroidism, hepatitis, and factors that don’t fit into other categories. undiagnosed (5-15%) despite exhaustive studies. 3
- 4. • Classical PUO • Nosocomial PUO • Neutropenic PUO • HIV-Associated • Transplant
- 5. • Classical PUO: It is defined as an unexplained fever that lasts for 3 weeks in previous Healthy people. • Nosocomial PUO: In hospital patients with fever of 101 F on several occasions caused by a process not present on admission where initial cultures are negative and diagnosis unknown after 3 days investigation. • Neutropenic PUO includes patients with fever as PUO defination, with <1 x 109 (10 power 9) neutrophils with initial negative cultures and diagnosis uncertain after 3 days.
- 6. • HIV-associated PUO includes HIV-positive patients with fever for 4 weeks as outpatients or 3 days as inpatients, with an uncertain diagnosis after 3 days investigation where at least 2 days have been allowed for cultures to incubate • Transplant PUO: May be due to infections , episodes of graft rejection in solid organ transplant recipients or in GVHD in hematopoietic stem cell transplantation.
- 7. TYPES Classical Nosocomal Neutropenic HIV Transplant Causes • diseases that affect connective tissue, • Leukemia • Infections • pulmonary embolism • enterocolitis • sinusitis • deep vein thrombosis • septic thrombophlebiti s Oppurtunitisic infections . Fungal infection Bacterial infection • Toxoplasmosis • Pnemcystiis jer.(cariini) • Cryptochoccosi s • Salmonellosis • Histoplasmosis • Cmv • Non Hodgikin lymphoma • Drug induced • Tuberculosis( 2ndry) 0-1 month-- bacterial or fungal infection 1-6month CMV ,opportunistic infections >6 Month bacterial pneumonia, community acquired infections .
- 8. • A patient looks well • Bizarre temperature chart with absence of diurnal variation &/or temperature related changes in pulse rate • Temperature >41°C • Absence of sweating during defervescence • Normal ESR and CRP despite high fever • Evidence of self injection or self harm • Normal temperature during supervised
- 9. Baseline Investigations • CBC with differential count and Blood film • ESR and CRP • Urine analysis • Liver function tests ,bilirubin and LDH( hepatitis markers if LFTs are suggestive) • Blood culture (3 times) and urine culture • ANA and rheumatoid factor • HIV antibodies • CXR • CT chest and abdomen Microscopic Investigations Immunological tests Atypical lymphocytes( EBV,CMV,HIV-1, hepatitis , Toxoplasma) , trypanosomiasis. Sputum for mycobacteria and fungi Stool for ova ,cysts and parasites Urine for WBCs, RBCs, schistosoma ova , mycobacteria( early morning urine*3) •Serology • for viruses, dimorphic fungi and some bacteria and protozoa • Connective Tissue disorders: ANA, DNA , complement levels, immunoglobulins ,cryoglobulins •Serology for Brucellosis, CMV infection, EBV infectious mononucleosis, HIV infection, amebiasis, toxoplasmosis, and chlamydial diseases Interferon gamma release assaydiagnosis of tuberculosisSerum protein electrophoresis Serum ferritin levels are useful in cases of FUO due to malignancies, SLE flare, and adult Still disease.
- 10. Test should only be performed when there is a Reasonable pretest probability of the condition investigated being present.Not all Tests should be done at once.
- 12. • Ensure a thorough history, examination and baseline investigation panel have been done. • Return to the patient's history and examination at regular intervals. • Consider non-infectious causes of a fever early on in the patient's journey. • All patients with PUO should have an HIV test. • Exclude malaria in patients with a history of relevant travel within the last 2 years.
- 13. • A positive tuberculin or interferon gamma release assay is not diagnostic for TB: microbiological confirmation through bacterial culture or molecular testing is required. • Be cautious with the interpretation of some serological tests as some perform poorly with high false positive and false negative rates. • Do not perform serological testing if there is no history of exposure to the pathogen you are testing for. • Perform PET-CT testing early in the patient's diagnostic journey when there are no localising clues in the history or examination.
- 14. • Therapeutic trials of antimicrobials or steroids are not recommended because they can mask symptoms and signs of the underlying disease process. • There are Three occasions when empirical treatment is appropriate: antituberculous therapy for suspected miliary or CNS TB, antimicrobials for patients with suspected infective endocarditis and signs of sepsis. • steroid treatment for possible temporal arteritis.
- 15. • Ensure that the patient is aware of the strong possibility of no diagnosis being made.