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Fever of Unknown Origin: Differential Diagnoses & Workup
Updated: Sep 23, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Atypical mycobacterial infection
Bubonic plague
Clostridial necrotizing fasciitis
Eosinophilic toxocariasis
Fungal infections of the genitourinary tract
Gallbladder gangrene
Heroin abuse
Lung cancer
Lyssavirus infection
Picornavirus infection
Pneumoconiosis
Retroviral infections
Rhinocerebral phycomycosis
Sepsis
Sphenoid sinusitis
Thrombophlebitis
Thyroid carcinoma
Trypanosoma infection
TB of the genitourinary tract
UTI
Venereal warts
Osteomyelitis
Rat-bite fever (S minor)
Malassezia furfur infection
C burnetii infection
Malignant histiocytosis
Drug fever
Factitious fever
Kikuchi disease
Workup
Laboratory Studies
- CBC count and microscopic examination
- Anemia is an important finding and suggests a serious underlying disease.
- Ensure that leukemias are not missed in aleukemic or preleukemic cases.
- Suspect herpesvirus infection if the patient has lymphocytosis with atypical cells.
- A leukocytosis with an increase in bands suggests an occult bacterial infection.
- Diagnose malaria and spirochetal diseases with the aid of direct examination of the peripheral blood smear; however, repeated examinations are often necessary.
- Urinalysis: Exclude UTIs and malignant tumors of the urinary tract; however, not all of them are consistently associated with pathologic findings in the urine.
- Serum chemistry
- At least one liver function test result is usually abnormal, with an underlying disease originating in the liver or a disease that causes nonspecific alterations of the liver (eg, granulomatous hepatitis).
- Most other chemistry tests rarely contribute to the diagnosis, although they are frequently ordered.
- Cultures
- Blood cultures for aerobic and anaerobic pathogens are essential in the evaluation; however, no more than 6 sets of blood cultures are required. Routinely culture the patients' urine.
- Cultures of sputum and stool may be helpful in the presence of signs or symptoms suggestive of pulmonary or gastrointestinal disease, respectively.
- Obtain cultures for bacteria, mycobacteria, and fungi in all normally sterile tissues and liquids that are sampled during further workup. These tissues and fluids include cerebrospinal fluid (CSF), pleural or peritoneal fluid, and fluid from the liver, bone marrow, and lymph nodes.
- Serologies
- Serologies are most helpful if paired samples show a significant, usually 4-fold, increase of antibodies specific to an infectious microorganism. Brucellosis, CMV infection, infectious mononucleosis, HIV infection, amebiasis, toxoplasmosis, and chlamydial diseases are diagnosed with serology.
- These diagnostic tests are of limited value in most patients with fever of unknown origin (FUO), but they are appropriate for evaluation of the above illnesses in the correct clinical and epidemiological setting.
- Other tests
- Frequently check antinuclear antibody (ANA) titers, rheumatologic factor, thyroxine level, and ESR because they are helpful in diagnosing certain conditions (lupus, RA, thyroiditis, hyperthyroidism, GCA, PMR). Their diagnostic accuracy is limited in other autoimmune and collagen vascular diseases.
- In patients in whom GCA and PMR are suspected, checking the ESR may be particularly useful because the ESR is nearly always greater than 60 mm/h (and often is much higher, especially in GCA).
Imaging Studies
- Chest radiography: Routinely obtain chest radiography.
- Abdominal ultrasonography: Routine abdominal ultrasonography may also be justified, even in the absence of signs of an intra-abdominal process. However, negative ultrasonographic findings and absent symptoms suggestive of an intra-abdominal process do not exclude such a process.
- CT scanning
- If ultrasonography fails to help reveal the diagnosis, obtain CT scans of the abdomen in all patients with symptoms suggesting an intra-abdominal process, in patients with suspected retroperitoneal tumors or infections, and in those with abnormal findings on liver function tests.
- Intravenous pyelography may be more sensitive than CT scanning in detecting processes involving the descending urinary tract, but CT scanning is preferred for most other processes of the retroperitoneal space.
- MRI: This can be very useful when osteomyelitis is suspected. MRI has also been used in the diagnosis of vasculitides.
Other Tests
- Endoscopic examination
- Perform an endoscopic examination of the upper and lower gastrointestinal tract, including retrograde cholangiography when indicated or when searching for Crohn disease, Whipple disease, biliary tract disease, and gastrointestinal tumors.
- Occasionally, complementing endoscopic studies with barium enemas or upper gastrointestinal series is necessary.
- Radionucleotide studies
- Perform ventilation and perfusion radionucleotide studies to document pulmonary emboli.
- Obtain a pulmonary angiography when suspecting pulmonary emboli, despite negative scanning studies.
- A technetium bone scan may be a more sensitive method for documenting skeletal involvement when suspecting osteomyelitis in a patient without compatible changes in conventional radiography.
- Consider radionucleotide studies using gallium citrate or granulocytes labeled with indium In 111 for diagnosis of occult abscesses, neoplasms, or soft-tissue lymphomas.
- Positron emission tomography (PET) scanning: This has enhanced the detection of occult neoplasms, lymphomas, and vasculitides in patients with FUO.
- Echocardiography: This technique is highly sensitive in diagnosing endocarditis, particularly when transesophageal echocardiography is available.
Procedures
- The final diagnosis is obtained during direct biopsy examination of involved tissue. Biopsies are easily performed in enlarged accessible lymph nodes, other peripheral tissues, and bone marrow.
- The decision to biopsy is more difficult if it necessitates an exploratory surgical procedure (eg, laparotomy). This is rarely indicated (eg, when imaging techniques are nondiagnostic and an intra-abdominal source is suspected).
- Liver biopsy rarely yields helpful data in patients without abnormal liver function tests or abnormal liver findings (observed on CT scan or ultrasonography).
More on Fever of Unknown Origin |
| Overview: Fever of Unknown Origin |
 Differential Diagnoses & Workup: Fever of Unknown Origin |
| Treatment & Medication: Fever of Unknown Origin |
| Follow-up: Fever of Unknown Origin |
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References
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Further Reading
Keywords
fever of unknown origin, FUO, febris, pyrexia, febrile illness, idiopathic fever, fever of undetermined origin, high temperature, feverish, bacteremia, bacterial disease, tuberculosis, urinary tract infection, UTI, endocarditis, hepatobiliary infection, osteomyelitis, Borrelia recurrentis, B recurrentis, Spirillum minor, S minor, Borrelia burgdorferi, B burgdorferi, Treponema pallidum, T pallidum, Rickettsia, Coxiella burnetii, C burnetii, chronic Q fever, Q fever endocarditis, rickettsial disease, Lyme disease, syphilis, rat-bite fever, ratbite fever, rat bite fever, herpes, herpes virus, acquired immunodeficiency syndrome, AIDS, human immunodeficiency virus, HIV, collagen vascular disease, autoimmune disease, granulomatous disease, drug fever, relapsing fever, hyperthyroidism, subacute thyroiditis, factitious fever
