Dr Akhil Suresh junior resident OLD DEFINITION Petersdorf and Beeson in 1961 An illness of more than 3 weeks duration With fever of more than or equal to 383 0 C ID: 1035946
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1. Fever of unknown origin Dr Akhil Suresh junior resident
2. OLD DEFINITION Petersdorf and Beeson in 1961An illness of more than 3 weeks duration With fever of more than or equal to 38.3 0 C on two occasions And an uncertain diagnosis despite 1 week of inpatient care
3. NEW DEFINTITION Fever more than or equal to 38.30 C on at least 2 occasions Illness duration of more than 3 weeks No known immunocompromised state
4. 4. Diagnosis that remains uncertain after thorough history taking, physical examination and the following obligatory investigations ESR, CRPPlatelet count,TC,DC,HbRFT,LFT,LDH,creatine kinase,ferritinANA, RAFSPEP
5. URINE ANALYSIS BLOOD CULTURE (3)URINE CULTURECHEST X RAY, USG ABDOMENTUBERCULIN SKIN TEST OR INTERFERON GAMMA ASSAY RELEASE
6. ETIOLOGYINFECTIONS Bacterial- non specific Bacterial specificFungal Parasiticviral
7. Bacterial
8. Non infectious inflammatory diseases [NIID]Systemic rheumatic and autoimmune diseases VasculitisGranulomatous diseasesAutoinflammatory syndromes
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10. neoplasmsHematologicalSolidBenign
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12. Miscellaneous causes
13. DIFFERENTIAL DIAGNOSIS FUO is caused by an atypical presentation of a rather common disease than by a a very rare disease.Eg- endocarditis, diverticulitis, vertebral osteomyelitis and extrapulmonary tuberculosis
14. OTHER DISEASES TO CONSIDER Q fever – rural area, h/o heart valve disease, aortic aneurysm or vascular prosthesis Whipples disease- CNS+GIT+jointsTropics – malaria, leishmaniasis, histoplasmosis, coccidioidomycosis
15. CULTURE NEGATIVE ENDOCARDITISHACEK organismsCoxiella burnetiiBartonella spsT.whipplei
16. STERILE ENDOCARDITISSLEAPLAMARANTIC – paraneoplastic sterile thrombotic disease in adenocarcinoma
17. NIIDs- most common ones include Large vessel vasculitisPolymyalgia rheumaticaFamilial mediteranian fever Adult onset still’s disease
18. SCHNITZLER SYNDROMEUrticariaBone painMonoclonal gammopathyFUO
19. NEOPLASMSMalignant lymphoma is the most common causeFever starts even before lymphadenopathy
20. DRUG INDUCED FEVER Fever + eosinophilia+ lymphadenopathy DRESS- drug reaction with eosinophilia and systemic symptomsAllopurinol , carabamazepine, lamotrigine, phenytoin, sulfasalazine,furosemide,antimicrobials( like minocycline, vancomycin, isoniazid),quinidine, nevirapine ,etc
21. Exercise induced hyperthermia – normal CRP, ESRFactitious fever- induced by the patient by injecting contaminated water
22. Fraudulent fever – normothermic, manipulates the thermometer Simultaneous measurements from different sites can rule it outDissociation between temperature and pulse rate
23. RECURRENT FEVER Recurrent episodes of fever Fever free interval of at least 2 to 3 weeks due to apparent remission of underlying disease in this intervalEtiology is found in less than 50% of the cases
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26. APPROACHLook for PDCPDC- any localising sign, symptom or abnormal test that points towards a specific diagnosis Helps to narrow the area to search
27. HISTORY – pattern, duration, previous, drug , family, sexual, travel,exposure and animal contact EXAMINATION –eyes, lymph nodes, temporal arteries, liver , spleen, sites of previous surgery, skin and mucous membrane
28. Stop all drugs before investigation USG abdomen, CXR-PA3 BLOOD CULTURES 1 URINE CULTURERepeated culture is essential if the previously cultured samples were collected during AMD/CS therapy or within one of their discontinuation
29. To be included in the presence of PDCs- serology, ECHO,upper GI endoscopy, sinus radiography and bronchoscopyRepeat history and physical examination regularlyInvestigation of cryoglobulin appears to be a very valuable screening test (low cost)
30. Fever persisting beyond 72 hours after discontinuation of a drug is unlikely to be caused by that drug Multiple blood samples should be cultured in the lab for longer periods to ensure the growth of fastidious organisms
31. FUO with headache CSF examination Rule out HSV, M. TB,cryptococcus neoformans TB meningitis – low glucose <45 mg % -- high protein 100 to 500 mg % cell count 100 to 500
32. TST may be negative – miliary TB, malnutrition, immunosupresssion TST sensitivity is same as that of IGRA In miliary TB do liver bx for AFB, Cultutre, PCR (highest diagnostic yield )
33. In case of recurrent fever look for clues to recurrent syndromes All tests should be done or repeated during symptomatic phase If the duration is more than two years it is probably not infection or malignancy
34. SCINTIGRAPHYA non invasive technique to allow detection of foci in all parts of the body on the basis of functional changes in tissues Ga 67 citrate / In 111/99mTc labelled leukocyte scintigraphy
35. Not useful in early phase due to lack of substantial pathologic changesReadily allows whole body imaging
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37. PET scan FDG –flurodeoxyglucose Accumulates in tissues with high rate of glycolysis normal intake – brain, heart, bowel, kidney and bladder Malignant cells and activated leucocytes
38. In fever bone marrow shows increased uptake due to cytokine activation as a result of upregulation of glucose transporters Higher resolution and greater sensitivity in chronic low grade infection Higher accuracy in central skeleton
39. Vascular intake is increased in vasculitis Difficult to distinguish between infection, inflammation and malignancyAids targeted bxAlways stop CS because it decreases the pathological uptake in lymph nodes and vasculitis
40. Disadvantages availabilityExpense maybe cost effective n early stages to reduce hospital stay
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42. LATE TESTS LN BxSkin BxPulmonary wedge excision , excised tonsil histology and peritoneal bxScreening chest CT ( has 80% specificity but doesn’t add much to FDG PET CT)Screening abdominal CT ( only 65% specific )
43. BM aspiration only with PDCLiver bx more complicated, do with PDCs ,abnormal LFT is not an indication Temporal artery bx- giant cell arteritisPreferred in all with FUO with headache in more than 55 years Other late stage diagnostics are more expensive
44. FINAL WORD Failure to recognize PDC can cause a diagnostic delay If the patient is stable in between wait for newer PDCs to appear If the patient is unstable do further work up
45. TREATMENT Avoid empirical therapy unless the patient is rapidly deteriorating AMD ATT diminish the ability to culture fastidious bacteria/ mycobacteria AMD use only if neutropenia/ hemodynamically unstable ATT- TST +/suspicious of miliary TB
46. If fever doesn’t respond to 6 week empirical ATT go for other diagnosis COLCHICINE can prevent attacks of FMFNot effective once attack has started Non reliable response
47. EARLY COTICOSTEROIDSMasks symptomsCan lead to failure to diagnose life threatening infections or malignant lymphoma
48. NSAIDsSupportive Dramatic response may be see in adult onset stills disease
49. ANAKINRA- last ditch Recombinant IL-1 receptor antagonist Blocks IL-1alpha, IL-1betaUsed in anti inflammatory syndromes- FMF, hyper IgD syndrome, Schintzler’s syndromeMonotherapy improves symptoms without CS side effects in most of the chronic inflammatory conditions
50. PROGNOSIS Most FUO related death occurs due to malignancy (NHL)Otherwise death is rare in FUO
51. THANKYOU