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| {{Infobox_Disease | | | __NOTOC__ |
| Name = {{PAGENAME}} |
| | {{Siren|Fever of unknown origin}} |
| Image = |
| | {{Fever of unknown origin}} |
| Caption = |
| | {{CMG}}{{NE}} {{YH}} |
| DiseasesDB = |
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| ICD10 = {{ICD10|R|50||r|50}} |
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| ICD9 = {{ICD9|780.6}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = 003090 |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| MeshID = D005335 |
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| {{Search infobox}} | |
| {{CMG}} | |
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| | {{SK}} febris continua e causa ignota; febris e causa ignota; febris E.C.I.; fever/pyrexia of obscured/undetermined/uncertain/unidentifiable/unknown focus/origin/source; fever/pyrexia without a focus/origin/source; FUO; PUO |
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| '''Fever of unknown origin (FUO)''', '''pyrexia of unknown origin (PUO)''' or '''febris e causa ignota (febris E.C.I.)''' refers to a condition in which the patient has an elevated temperature but despite investigations by a physician no explanation has been found.<ref name="Mandell">
| | ==[[Fever of unknown origin overview|Overview]]== |
| [http://www.ppidonline.com/ Mandell's Principles and Practices of Infection Diseases] 6th Edition (2004) by Gerald L. Mandell MD, MACP, John E. Bennett MD, Raphael Dolin MD, ISBN 0-443-06643-4 · Hardback · 4016 Pages Churchill Livingstone </ref><ref name="Harrison">[http://books.mcgraw-hill.com/medical/harrisons/ Harrison's Principles of Internal Medicine] 16th Edition, The McGraw-Hill Companies, ISBN 0-07-140235-7</ref><ref name="Oxford"> [http://www.oup.com/us/catalog/general/subject/Medicine/PrimaryCare/?ci=0192629220&view=usa The Oxford Textbook of Medicine] Edited by David A. Warrell, Timothy M. Cox and John D. Firth with Edward J. Benz, Fourth Edition (2003), Oxford University Press, ISBN 0-19-262922-0</ref><ref name="Cecil">
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| [http://www.cecilmedicine.com/buy.cfm?book=goldman Cecil Textbook of Medicine] by Lee Goldman, Dennis Ausiello, 22nd Edition (2003), W.B. Saunders Company, ISBN 0-7216-9652-X</ref><ref name="IrwinRippe"> [http://www.lww.com/product/?0-7817-3548-3 Irwin and Rippe's Intensive Care Medicine] by Irwin and Rippe, Fifth Edition (2003), Lippincott Williams & Wilkins, ISBN 0-7817-3548-3</ref>
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| If the cause is found it usually is a [[diagnosis of exclusion]], that is, by eliminating all possibilities until only one explanation remains, and taking this as the correct one.
| | ==[[Fever Of unknown Origin historical perspective|Historical Perspective]]== |
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| == Definition == | | ==[[Fever of unknown origin classification|Classification]]== |
| In 1961 Petersdorf and Beeson suggested the following criteria:<ref name="Mandell"/><ref name="Harrison"/>
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| * Fever higher than 38.3°C (101°F) on several occasions
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| * Persisting without diagnosis for at least 3 weeks
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| * At least 1 week's investigation in hospital
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| Presently FUO cases are codified in four subclasses.
| | ==[[Fever of unknown origin pathophysiology|Pathophysiology]]== |
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| === Classic FUO === | | ==[[Fever of unknown origin causes|Causes]]== |
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| This refers to the original classification by Petersdorf and Beeson. The outpatient setting has been included to reflect current medical practise. The current definition requires three outpatient visits or three days in hospital or 1 week of "intelligent and invasive" ambulatory investigation.<ref name="Harrison"/> Studies show there are five categories of conditions: [[infection]]s (i.e. abscesses, [[endocarditis]], [[tuberculosis]], and complicated [[urinary tract infection]]s), [[neoplasm]]s (i.e. [[lymphoma]]s, [[leukaemia]]s), [[connective tissue disease]]s (i.e. [[temporal arteritis]] and [[polymyalgia rheumatica]], [[Still's disease]], [[systemic lupus erythematosus]], and [[rheumatoid arthritis]]), miscellaneous disorders (i.e. [[alcoholic hepatitis]], [[granuloma]]tous conditions), and undiagnosed conditions.<ref name="Mandell"/><ref name="Oxford"/>
| | ==[[Fever of unknown origin differential diagnosis|Differentiating Fever of unknown origin from other Diseases]]== |
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| The new definition is broader, stipulating three outpatient visits or 3 days in the hospital without elucidation of a cause or 1 week of "intelligent and invasive" ambulatory investigation.
| | ==[[Fever of unknown origin epidemiology and demographics|Epidemiology and Demographics]]== |
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| ===Nosocomial=== | | ==[[Fever of unknown origin risk factors|Risk Factors]]== |
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| Nosocomial FUO refers to [[pyrexia]] in patients that have been admitted to hospital for at least 24 hours. This is commonly related to hospital associated factors such as, surgery, use of [[urinary catheter]], intravascular devices (i.e. "drip", [[pulmonary artery catheter]]), drugs (antibiotics induced ''[[Clostridium difficile]]'' colitis, and [[drug fever]]), immobilization (decubitus, thromboembolic event). [[Sinusitis]] in the [[intensive care unit]] is associated with nasogastric and orotracheal tubes.<ref name="Mandell"/><ref name="Harrison"/><ref name="Oxford"/> Other conditions that should be considered are deep-vein thrombophlebitis, and [[pulmonary embolism]], [[transfusion reaction]]s, [[acalculous cholecystitis]], [[thyroiditis]], [[alcohol]]/[[drug withdrawal]], [[adrenal insufficiency]], [[pancreatitis]].<ref name="Harrison"/>
| | ==[[Fever of unknown origin screening|Screening]]== |
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| ===Immune-deficient=== | | ==[[Fever of unknown origin natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| Immunodeficiency can be seen in patients receiving [[chemotherapy]] or in hematologic malignant neoplasms. Fever is concommittent with [[neutropenia]] ([[neutrophil]] <500/uL) or impaired cell-mediated immunity. The lack of immune response masks a potentially dangerous course. Infection is the most common cause.<ref name="Mandell"/><ref name="Harrison"/><ref name="Oxford"/>
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| ===Human immunodeficiency virus (HIV)-associated===
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| {{see|Human immunodeficiency virus}}
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| HIV-infected patients are a subgroup of the immunodeficient FUO, and frequently have fever. The primary phase shows fever since it has a [[mononucleosis]]-like illness. In advanced stages of infection fever mostly is the result of a superimposed illness.<ref name="Mandell"/><ref name="Harrison"/><ref name="Oxford"/>
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| ==Some important causes==
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| Extrapulmonary tuberculosis is the most frequent cause of FUO.<ref name="Harrison"/>
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| Drug fever, as sole symptom of an adverse reaction to medication, should always be thought of. Disseminated granulomatoses such as [[Tuberculosis]], [[Histoplasmosis]], [[Coccidioidomycosis]], [[Blastomycosis]] and [[Sarcoidosis]] are associated with FUO.
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| [[Lymphoma]]s are the most common cause of FUO in adults. Thromboembolic disease (i.e. [[pulmonary embolism]], [[deep venous thrombosis]]) occasionally shows [[fever]]. Although infrequent, its potentially lethal consequences warrant evaluation of this cause. [[Endocarditis]], although uncommon, is another important thing to consider. An underestimated reason is factitious [[fever]]. Patients frequently are women that work, or have worked, in the medical field and have complex [[medical history|medical histories]].<ref name="Mandell"/>
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| ==Diagnosis== | | ==Diagnosis== |
| | [[Fever of unknown origin diagnostic study of choice|Diagnostic study of choice]] | | [[Fever of unknown origin history and symptoms|History and Symptoms]] | [[Fever of unknown origin physical examination|Physical Examination]] | [[Fever of unknown origin laboratory findings|Laboratory Findings]] | [[Fever of unknown origin electrocardiogram|Electrocardiogram]] | [[Fever of unknown origin x ray|X-Ray Findings]] | [[Fever of unknown origin echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Fever of unknown origin CT scan|CT-Scan Findings]] | [[Fever of unknown origin MRI|MRI Findings]] | [[Fever of unknown origin other imaging findings|Other Imaging Findings]] | [[Fever of unknown origin other diagnostic studies|Other Diagnostic Studies]] |
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| A comprehensive and meticulous history (i.e. illness of family members, recent visit to the tropics, medication), repeated physical examination (i.e. [[skin rash]], [[eschar]], [[lymphadenopathy]], [[heart murmur]]) and a myriad of laboratory tests (serological, [[blood culture]], immunological) are the cornerstone of finding the cause.<ref name="Mandell"/><ref name="Oxford"/>
| | ==Treatment== |
| | | [[Fever of unknown origin medical therapy|Medical Therapy]] | [[Fever of unknown origin interventions|Interventions]] | [[Fever of unknown origin surgery|Surgery]] | [[Fever of unknown origin primary prevention|Primary Prevention]] | [[Fever of unknown origin secondary prevention|Secondary Prevention]] | [[Fever of unknown origin cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Fever of unknown origin future or investigational therapies|Future or Investigational Therapies]] |
| Other investigations may be needed. [[Ultrasound]] may show [[cholelithiasis]], [[echocardiography]] may be needed in suspected [[endocarditis]] and a [[CT scan]] may show [[infection]] or malignancy of internal organs. Another technique is Gallium-67 scanning which seems to visualize chronic infections more effectively. Invasive techniques (biopsy and laparotomy for pathological and bacteriological examination) may be required before a definite diagnosis is possible.<ref name="Mandell"/><ref name="Oxford"/>
| | ==Case Studies== |
| | | [[Fever of unknown origin case study one|Case #1]] |
| [[Positron Emission Tomography]] using radioactively labelled [[Fluorodeoxyglucose]] (FDG) has been reported to have a [[Sensitivity (tests)|sensitivity]] of 84% and a [[Specificity (tests)| specificity]] of 86% for localizing the source of fever of unknown origin.<ref>{{cite journal | author = Meller J, Altenvoerde G, Munzel U, Jauho A, Behe M, Gratz S, Luig H, Becker W | title = Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET. | journal = Eur J Nucl Med. | volume = 27| issue = 11 | pages = 1617-25 | year = 2000 | id = PMID 11105817}}</ref> | |
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| Despite all this, diagnosis may only be suggested by the therapy chosen. When a patient recovers after discontinuing medication it likely was [[drug fever]], when antibiotics or antimycotics work it probably was infection. Empirical therapeutic trials should be used in those patients in which other techniques have failed.<ref name="Mandell"/>
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| ==Therapy==
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| Unless the patient is acutely ill, no therapy should be started before the cause has been found. This is because non-specific therapy rarely is effective and mostly delays diagnosis. An exception is made for neutropenic patients in which delay could lead to serious complications. After blood cultures are taken this condition is aggressively treated with broad-spectrum antibiotics. Antibiotics are adjusted according to the results of the cultures taken.<ref name="Mandell"/><ref name="Harrison"/><ref name="Oxford"/>
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| HIV-infected persons with pyrexia and [[hypoxia (medical)|hypoxia]], will be started on medication for possible [[Pneumocystis pneumonia|''Pneumocystis jirovecii'' infection]]. Therapy is adjusted after a diagnosis is made.<ref name="Oxford"/>
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| ==Prognosis==
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| Since there is a wide range of conditions associated with FUO, prognosis depends on the particular cause.<ref name="Mandell"/> If after 6 to 12 months no diagnosis is found, the chances diminish of ever finding a specific cause.<ref name="Oxford"/> However, under those circumstances prognosis is good.<ref name="Harrison"/>
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| ==References== | |
| <references/>
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| [[it:Febbre da causa ignota]] | |
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| [[Category:Infectious disease]]
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| [[Category:Medical signs]]
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| [[Category:Symptoms]]
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| [[Category:Ailments of unknown etiology]] | | [[Category:Ailments of unknown etiology]] |
| [[Category:Signs and symptoms]] | | [[Category:Signs and symptoms]] |
| {{WH}}
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