Fever of unknown origin
Fever of unknown origin | |
---|---|
Other names | Pyrexia of unknown origin, febris e causa ignota |
Types | Various |
Fever of unknown origin (FUO) refers to a condition in which the patient has an elevated temperature (fever) but, despite investigations by one or more qualified physicians, no explanation is found.[1][2][3]
If the cause is found it is usually a diagnosis of exclusion, eliminating all possibilities until only the correct explanation remains.
Causes
Worldwide, infection is the leading cause of FUO with prevalence varying by country and geographic region.[4] Extrapulmonary tuberculosis is the most frequent cause of FUO.[2] Drug-induced hyperthermia, as the sole symptom of an adverse drug reaction, should always be considered. Disseminated granulomatoses such as tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis and sarcoidosis are associated with FUO. Lymphomas 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 possible. Bartonella infections are also known to cause fever of unknown origin.[5]
Endemic mycoses such as
Cancer can also cause fever of unknown origin. This is thought to be due to release of pyrogenic cytokines from cancer cells as well as due to spontaneous tumor necrosis (sometimes with secondary infections).
In those with
Auto-inflammatory and auto-immune disorders account for approximately 5-32% of fevers of unknown origin.
Infection
Neoplasm
Although most neoplasms can present with fever, malignant lymphoma is by far the most common diagnosis of FUO among the neoplasms.[7] In some cases the fever even precedes lymphadenopathy detectable by physical examination.[7]
Neoplasm cause | Disease name |
---|---|
Hematologic malignancies |
|
Solid tumors |
|
Benign |
|
Noninfectious inflammatory diseases
Miscellaneous conditions
- ADEM (acute disseminated encephalomyelitis)[7]
- Adrenal insufficiency[7]
- Aneurysm[7]
- Anomalous thoracic duct[7]
- Aortic dissection[6]
- Aortic-enteral fistula[7]
- Aseptic meningitis (Mollaret's syndrome)[7]
- Atrial myxoma[7]
- Brewer's yeast ingestion[7]
- Caroli disease[7]
- Cholesterol emboli[7]
- Complex partial status epilepticus[7]
- Cyclic neutropenia[7]
- Erdheim–Chester disease[7]
- Extrinsic allergic alveolitis[7]
- Factitious disease[6][7]
- Fire-eater's lung[7]
- Fraudulent fever[7]
- Gaucher's disease[7]
- Hamman–Rich syndrome (acute interstitial pneumonia)[7]
- Hashimoto's encephalopathy[7]
- Hemoglobinopathies[6]
- Hypersensitivity pneumonitis[7]
- Hypertriglyceridemia[7]
- Hypothalamic hypopituitarism[7]
- Idiopathic normal-pressure hydrocephalus[7]
- Inflammatory pseudotumor[7]
- Kikuchi's disease[6][7]
- Linear IgA dermatosis[7]
- Laennec's cirrhosis[6]
- Mesenteric fibromatosis[7]
- Metal fume fever[7]
- Milk protein allergy[7]
- Myotonic dystrophy[7]
- Nonbacterial osteitis[7]
- Organic dust toxic syndrome[7]
- Panniculitis[7]
- POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes)[7]
- Polymer fume fever[7]
- Post–cardiac injury syndrome[7]
- Postmyocardial infarction syndrome[6]
- Primary biliary cirrhosis [7]
- Primary hyperparathyroidism[7]
- Recurrent pulmonary emboli[6]
- Pyoderma gangrenosum[7]
- Retroperitoneal fibrosis [7]
- Rosai-Dorfman disease[7]
- Sclerosing mesenteritis[7]
- Silicone embolization[7]
- Subacute thyroiditis (de Quervain's)[6][7]
- Sweet syndrome (acute febrile neutrophilic dermatosis)[7]
- Thrombosis[7]
- Tubulointerstitial nephritis and uveitis syndrome (TINU)[7]
- Tissue infarction/necrosis[6]
- Ulcerative colitis[7]
Inherited and metabolic diseases
- Adrenal insufficiency[6]
- Cyclic neutropenia[6]
- Deafness, urticaria, and amyloidosis[6]
- Fabry disease[6]
- Familial cold urticaria[6]
- Familial Mediterranean fever[6][7]
- Muckle–Wells syndrome[6]
- Tumor necrosis factor receptor–associated periodic syndrome (familial Hibernian fever)[6][7]
- Type V Hypertriglyceridemia[6]
Thermoregulatory disorders
Thermoregulatory disorders | Location |
---|---|
Central |
|
Peripheral |
Habitual hyperthermia
- Exaggerated circadian rhythm[6]
Other
- “Afebrile” FUO [<38.3 °C (100.9 °F)][6]
Diagnosis
A comprehensive and meticulous history (i.e. illness of family members, recent visit to the tropics, medication), repeated physical examination (i.e.
Other investigations may be needed. Ultrasound may show
Despite all this, diagnosis may only be suggested by the therapy chosen. When a patient recovers after discontinuing medication it likely was
Definition
There is no universal agreement with regards to time criteria or other diagnostic criteria to diagnose a fever of unknown origin and various definitions have been used.[4]
In 1961 Petersdorf and Beeson suggested the following criteria:[1][2]
- Fever higher than 38.3 °C (101 °F) on several occasions
- Persisting without diagnosis for at least 3 weeks
- At least 1 week's investigation in hospital
A new definition which includes the outpatient setting (which reflects current medical practice) is broader, stipulating:
- 3 outpatient visits or
- 3 days in the hospital without elucidation of a cause or
- 1 week of "intelligent and invasive" ambulatory investigation.[2]
Presently FUO cases are codified in four subclasses.
Classic
This refers to the original classification by Petersdorf and Beeson. Studies show there are five categories of conditions:[citation needed]
- infections (e.g. abscesses, endocarditis, tuberculosis, and complicated urinary tract infections),
- leukaemias),
- systemic lupus erythematosus, and rheumatoid arthritis),
- miscellaneous disorders (e.g. alcoholic hepatitis, granulomatous conditions), and
- undiagnosed conditions.[1][3]
Nosocomial
Nosocomial FUO refers to
Immune-deficient
Immunodeficiency can be seen in patients receiving chemotherapy or in hematologic malignancies. Fever is concomitant 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.[1][2][3]
Human immunodeficiency virus (HIV)-associated
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 infections.[1][2][3]
Treatment
Unless the patient is acutely ill, no therapy should be started before the cause has been found. This is because non-specific therapy is rarely effective and may delay the diagnosis. An exception is made for neutropenic (low white blood cell count) patients or patients who are severely immunocompromised in which delay could lead to serious complications.[4] 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.[1][2][3]
HIV-infected people with pyrexia and
Prognosis
Since there is a wide range of conditions associated with FUO, prognosis depends on the particular cause.[1] If after six to twelve months no diagnosis is found, the chances of ever finding a specific cause diminish.[3] Under those circumstances, the prognosis is good.[2]
See also
- Chronic fatigue syndrome
- Encephalitis lethargica
- Idiopathic chronic fatigue
- Idiopathic disease
References
- ^ a b c d e f g h i j k
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
- ^ ISBN 0-07-140235-7
- ^ ISBN 0-19-262922-0
- ^ S2CID 246487696.
- S2CID 14094482.
- ^ )
- ^ ISBN 978-0071802161.
- S2CID 6114482.