Pyrexia of unknown origin
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1. Pyrexia of unknown origin (PUO) is defined as a fever that persists for at least 3 weeks with an unknown source despite 1 week of inpatient investigations or 3 outpatient visits. (2) Common causes of PUO include infections (especially tuberculosis), malignancies, and collagen vascular diseases. 2. A thorough history, physical exam, and initial laboratory and imaging tests are used to identify potential sources and guide further testing. Additional tests may include lumbar puncture, bone marrow biopsy, liver biopsy, or exploratory laparotomy. 3. When the source remains unknown after extensive evaluation, infectious disease, rheumatology, or oncology consultations may help identify less common causes or guide further
![Original Definition(by Petersdorf and Beeson, 1961)Temperatures ≥ 38.3ºC (101ºF) on several occasionsFever ≥3 weeksFailure to reach a diagnosis despite 1 week of inpatient investigations or 3 outpatient visits [1 IP / 3 OP]](https://image.slidesharecdn.com/pyrexiaofunknownorigin-110401041639-phpapp01/85/Pyrexia-of-unknown-origin-2-320.jpg)
Pyrexia of unknown origin
- 1. Pyrexia of unknown originMOHD HANAFI RAMLEE
- 2. Original Definition(by Petersdorf and Beeson, 1961)Temperatures ≥ 38.3ºC (101ºF) on several occasionsFever ≥3 weeksFailure to reach a diagnosis despite 1 week of inpatient investigations or 3 outpatient visits [1 IP / 3 OP]
- 4. COMMON CAUSES OF PUO
- 5. Causes of FUO(in India)Infectious 53%#1: TB (45%)Neoplasm: 17%#1: NHL (47%)Collagen Vasc.: 11%#1 SLE: 45%Miscellaneous: 5%Undiagnosed: 14%Kejariwal D et al. J Postgrad Med. 2001 Apr-Jun; 47(2): 104-7.
- 6. FUO by the Decades1950s1970s1980s1990sMourad O et al. Arch Int Med. 2003 Mar 10;163(5):545-51.
- 7. Classic PUO3 common etiologies which account for themajority of classic PUO:InfectionsMalignanciesCollagen Vascular DiseaseOthers/Miscellaneous which includes drug-induced fever.
- 8. InfectionsBacterial: abscesses, TB, complicated UTI, endocarditis, osteomyelitis, sinusitis, Lyme disease, prostatitis, cholecystitis, empyema, biliary tract infection, brucellosis, typhoid, leptospirosis, Q fever, borreliosis, etc.Parasite: Malaria,toxoplamosis, leishmaniasis, etc.Fungal: histoplasmosis, etc.Viral: CMV, infectious mononucleosis, HIV, etc.
- 9. InfectionsAs duration of fever increases, infectious etiology decreasesMalignancy and factitious fevers are more common in patients with prolonged FUO.
- 10. MalignanciesHaematologicalLymphomaChronic leukemiaNon-haematologicalRenal cell cancerHepatocellular carcinomaPancreatic cancerColon cancerHepatomaMyelodysplastic SyndromeSarcomas
- 11. Collagen vascular disease / Autoimmune diseaseAdult Still's diseasePolymyalgia rheumaticaTemporal arteritisRheumatoid arthritisRheumatoid feverInflammatory bowel diseaseReiter's syndromeSystemic lupus erythematosusVasculitidesPolyarteritisnodosaGiant cell arteritisKawasaki diseaseStill’s disease
- 12. Others/miscellaneousDrugs: penicilin, phenytoin, captopril, allopurinol, erythromycin, cimetidine, etc.HyperthyroidismAlcoholic hepatitisSarcoidosisInflammatory bowel diseaseDeep Venous Thrombosis
- 13. Roth AR and Basello GM. Am Fam Physician. 2003 Dec 1;68(11):2223-8.
- 14. Nosocomial PUOMore 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 oro-tracheal tubes.
- 15. Prostatic abscess in a man with a urinary catheter.25% of non-infectious cause includes:Acalculouscholecystitis,
- 17. Pulmonary embolism. Neutropenic PUOPatients on chemotherapy or immune deficiencies are susceptible to:Opportunistic bacterial infection
- 18. Fungal infections such as candidiasis
- 21. Perianal infections. Examples of aetiological agent:aspergillus
- 22. Candida
- 23. CMV
- 24. Herpes simplexHIV-associated PUOHIV infection alone may be a cause of fever. Common secondary causes include:Tuberculosis
- 25. Toxoplasmosis
- 26. CMV infection
- 28. Salmonellosis
- 29. Cryptococcosis
- 30. Histoplasmosis
- 32. Drug-induced feverA Clinical ApproachPyrexia of Unknown Origin
- 33. History TakingHistory of Presenting Illness (HOPI)1。Onset- acute: Malaria, pyogenic infection- gradual: TB, thyphoid fever2。Characterhigh grade fever: UTI, TB, malaria, drug3。Patternsustained/persistent: Thyphoid fever, drugs
- 34. intermittent fever:Daily spikes: Abscess, TB, SchistosomiasisTwice-daily spikes: LeishmaniasisSaddleback fever: Leptospirosis, dengue,borrelia-relapsing/ recurrent fever: Non-falciparum malaria, Brucellosis, Hodgkin’s lymphoma4。Antecedents- prior to onset of fever: dental extraction: Infective endocarditisUrinary catherization: UTI, bacteremia.
- 35. 5。Associated symptomsChills & rigorsbacterial, rickettsial and protozoaldisease,influenza, lymphoma, leukaemia, drug-inducedNight sweatsTB, Hodgkin’s lymphomaLoss of weightMalignancy, TBCough and DyspnoeaMiliaryTB, multiple pulmonary emboli, AIDS patient with PCP, CMV.HeadacheGiant cell arteritis, typhoid fever, sinusitisJoint painRA, SLE, vasculitis
- 36. Abd. PainCholangitis, biliary obstruction, perinephric abscess, Crohn’s disease, dissecting aneuryms, gynaecological infectionBone painOsteomyelitis, lymphomaSorethroatIM, retropharyngeal abscess,post-Streptococcal infectionDysuria, rectal painProstatic abscess, UTIAltered bowel habit IBD, thyphoid fever, schistosomiasis, amoebiasisSkinrashGonococcalinfection, PAN，NHL, dengue fever
- 37. Past Medical HistoryMalignancy = leukemia, lymphoma, hepatocellular caHIV infectionDMIBDcollagen vascular disease-SLE, RA, giant cell arteritis TBHeart disease: valvular heart diseasePast Surgical HistoryPost splenectomy/ post- transplantationProsthetic heart valveCatheter, AV fistula Recent surgery/ operation
- 38. Drug HistoryImmunosuppressive drug/ corticosteroid Anticoagulants: accumulation of old blood in closed space e.g. retroperitoneal, perisplenicBefore fever: drug feveroccur within 3 months after starting taking drugs may cause hypersensitivity and low grade fever, usually associated with rashDue to the allergic reaction, direct effect of drug which impair temperature regulation (e.g. phenothiazine)E.g. Antiarrhythmic drug: procainamide, quinidine; Antimicrobacterial agent: penicillin, cephalosporin, hydralazineAfter fever: may modify clinical pictures, mask certain infection e.g. SBE, antibiotic allergyFamily HistoryAnyone in family has similar problem: TB, familial Mediterranian fever
- 39. Social HistoryTravel amoebiasis, typhoid fever, malaria, SchistosomiasisResidentalareamalaria, leptospirosis, brucellosisOccupation farmers, veterinarian, slaughter-house workers = Brucellosisworkers in the plastic industries = polymer-fume feverContact with domestic / wild animal / birds : Brucellosis, psittacosis (pigeons), Leptospirosis, Q fever, ToxoplasmosisDiet historyunpasteurized milk/cheese = Brucellosispoorly cooked pork = TrichinosisIVDU = HIV-AIDS related condition, endocarditisSexual orientation = HIV, STD, PIDClose contact with TB patients
- 40. Physical ExaminationPyrexia of Unknown Origin
- 41. ExaminationGeneralPattern of fever (continous, intermittent, relapsing)
- 42. Ill/not ill
- 43. Weight loss (chronic illness)
- 44. Skin rashHandsStigmata of Infective EndocarditisVasculitis changesClubbingPresence of arthropathyRaynaud’s phenomenon
- 45. ArmsDrug injection sites (ivdu)Epitrochlear and axillary nodes (lymphoma, sarcoidosis, focal infection)Skin
- 46. Head & neckFeel temporal arteries (tender & thicken)Eyes – iritis/conjuctivitis (ct disease – reiter syndrome)Jaundice (ascending cholangitis)Fundi – choroidal tubercle (miliarytb), roth’s spot (ie) and retinal haemorrhage (leukaemia)Lymphadenopathy
- 47. Face & mouthButterfly rashMucous membranesSeborrhoic dermatitis (hiv)Mouth ulcers (sle)Buccal candidiasisTeeth & tonsils infection (abscess)Parotid enlargementEars – otitis media
- 48. ChestBony tendernessCvs – murmurs (ie, atrial myxoma), rubs (pericarditis)Resp – signs of pneumonia, tb, empyema and lung ca
- 49. AbdomenRose coloured spot (typhoid fever)Hepatomegaly (sbp, hepatic ca, met)Splenomegaly (haemopoietic malignancy, ie, malaria)Renal enlargement (renal cell ca)Testicular enlargement (seminoma)Penis & scrotum – discharge/rashInguinal ligamentPer rectal exam – mass/tenderness in rectum/pelvis (abscess, ca, prostatitis)Vaginal Examination – collection of pelvic pus/ Pelvic Inflammatory Disease
- 51. Central Nervous SystemSigns of meningism (chronic tb meningitis)Focal neurological signs (brain abscess, mononeuritis multiplex in polyarteritisnodosa)
- 52. InvestigationPyrexia of Unknown Origin
- 53. Stage 1: Laboratory investigationsStage 1: (screening tests)Full blood countESR & CRPBUSELFTsBlood cultureSerum virologyUrinalysis and cultureSputum culture and sensitivityStool FEME and occult bloodCXRMantoux test
- 54. Stage 2: Laboratory investigationsStage 2:Repeat history and examinationProtein electrophoresisCT (chest, abdomen, pelvis)Autoantibody screen (ANA, RF, ANCA, anti-dsDNA)ECGBone marrow examinationLumbar punctureConsider PSA, CEATemporal artery biopsyHIV test counselling
- 55. Stage 3: Laboratory investigationsStage 3:EchocardiographyFurther Ix abdomen (Indium-labelled WC scan – IBD, abscesses, local sepsis)Barium studiesIVULiver biopsyExploratory laparotomyBronchoscopy
- 56. Treat TB, endocarditis, vasculitis, trial of aspirin/ steroidsStage 4: Laboratory investigations
- 57. Diagnosing Pyrexia of Unknown Origin
- 58. Imaging Studies
- 59. DiagnosisMore invasive testing, such as LP or biopsy of bone marrow, liver, or lymph nodes, should be performed only when clinical suspicion shows that these tests are indicated or when the source of the fever remains unidentified after extensive evaluation. When the definitive diagnosis remains elusive and the complexity of the case increases, an infectious disease, rheumatology, or oncology consultation may be helpful.