Fevers of Unknown Origin
Julie Adkins, Jill C. Cash, Beverly R. Byram, Cheryl A. Glass, Kristin Ownby, and Pat Obulaney
Definition
A.The criteria for fevers of unknown origin (FUO) are an illness of at least 3 weeks’ duration, fever over 101.0°F (38.3°C) on several occasions, and undiagnosed FUO after 1 week of study in the hospital. Because of cost factors, the criterion requiring 1 week of hospitalization is often bypassed.
Incidence
A.In adults, infections account for 20% to 40% of the cases, whereas cancer accounts for 7% to 20% of FUO cases. Autoimmune disorders occur with equal frequency in adults and children. Infection, cancer, and autoimmune disorders combined account for 20% to 25% of FUO in patients who have been febrile for 6 months or longer. Various miscellaneous diseases account for another 25%. Approximately 50% of FUO remain undiagnosed but have a benign course, with symptoms eventually resolving.
Pathogenesis
There are five categories of FUO causes.
A.Infection: Most common systemic infections are tuberculosis (TB) and endocarditis.
B.Neoplasms: Most common are lymphoma and leukemia.
C.Autoimmune disorders: Most common are Still’s disease, systemic lupus erythematosus (SLE), and polyarteritis nodosa.
D.Miscellaneous causes: Drug fever; hyperthyroidism, thyroiditis, sarcoidosis, Whipple’s disease, familial Mediterranean fever, recurrent pulmonary emboli, alcoholic hepatitis, drug fever, factitious fever, and others.
E.Undiagnosed FUO.
Predisposing Factors
A.Upper respiratory infection.
B.Urinary tract infection.
C.Viral illnesses.
D.Drug allergy, especially to antibiotics.
E.Connective tissue disease.
Common Complaints
A.The patient feels sick all over,
with malaise and fatigue.
B.The patient has chills all over the body with high fever.
Other Signs and Symptoms
A.Tachycardia.
B.Sensation of warmth or flushing.
C.Piloerection.
D.Myalgia.
E.Mild inability to concentrate, confusion, delirium, or even stupor.
F.Labial herpes simplex outbreak, or fever blisters.
Subjective Data
A.Review the onset, course, and duration of symptoms.
B.Review family, occupational, and social history.
C.Review sexual practices, including monogamy and oral, rectal, and vaginal sexual habits, recreational habits, and any new changes.
D.Elicit information regarding use of intravenous (IV) drugs.
E.Review if the patient has had this illness before. How was it treated?
F.Review travel during the past month.
G.Review any new hobbies, changes at home or work, or other new events.
H.Review the patient’s history for contact with any friends or family members who have been sick and do not seem to be getting any better, including exposure to TB.
I.Review the patient’s history for eating any uncooked meat and dietary changes during the past month.
J.Review for risk factors for thrombophlebitis (see Chapter 14).
K.Review fever pattern, duration, and magnitude. Acute fevers are less than 7 days in duration. Chronic or persistent fevers are greater than 2 weeks in duration.
L.Review immunization status.
M.Review medications both current and recent, including herbals and over-the counter (OTC) drugs. Chemotherapy or immunosuppressive medications place patient at higher risk for infection. Any history of antimicrobial use for current fever episode?
N.Any prosthetic devices.
Physical Examination
A.Check temperature, pulse, respirations, blood pressure, weight, and height. Is the patient tachycardic or heart rate within normal limits?
B.Inspect:
1.Conduct funduscopic exam to rule out retinopathy, Roth’s spots, and choroidal tubercles.
2.Examine the ears, nose, and throat. Inspect the mouth.
3.Observe the skin and mucous membranes.
C.Palpate:
1.Palpate the neck, axilla, and groin for lymphadenopathy.
2.Elderly: Palpate the scalp for tender arteries of temporal arteritis.
3.Palpate the thyroid gland.
4.Palpate the abdomen for organomegaly, masses, tenderness, guarding, rebound, suprapubic tenderness, and costovertebral angle (CVA) tenderness.
5.Palpate the musculoskeletal system for bone or joint swelling, tenderness, increased warmth; check lower extremities for evidence of phlebitis, asymmetrical swelling, calf tenderness, and palpable cord.
D.Percuss:
1.Percuss the sinuses for tenderness, and transilluminate for evidence of sinusitis.
2.Percuss the chest for consolidation.
3.Percuss the abdomen.
E.Auscultate:
1.Auscultate the heart for murmurs and rubs.
2.Auscultate the lungs for rales, consolidation, and effusion.
F.Neurologic exam:
1.Assess for signs of meningeal irritation (Brudzinski’s and Kernig’s signs), photosensitivity, and presence of focal deficits.
2.Conduct mental status exam.
G.Genitorectal exam, if applicable:
1.Female: Conduct pelvic exam for cervical discharge, adnexal masses, lesions, and pelvic inflammatory disease (PID) symptoms.
2.Male: Conduct prostate and testicular exam for tenderness and masses; check penis for discharge, rash, and lesions.
3.Both: Conduct rectal exam for discharge, tenderness, and masses; check stool for occult blood specimen.
4.Check the skin for rashes or wounds.
Diagnostic Tests
A.Complete blood count (CBC) with differential.
B.Erythrocyte sedimentation rate (ESR) and creactive protein (CRP).
C.Urinalysis and urine culture.
D.Complete metabolic panel.
E.Liver function test.
F.Blood cultures.
G.Consider serology for suspected infections or pathology (refer to Chapter 19). Suspected infections include Epstein–Barr virus, Q fever, Lyme disease or other tick-borne diseases, hepatitis, syphilis, and cytomegalovirus (CMV).
H.Suspected collagen disease: Antinuclear antibodies (ANA) and rheumatoid factor.
I.Suspected TB: Tuberculin skin test, sputum, and urine cultures.
J.Immunologic studies: enzyme-linked immunosorbent assay (ELISA), western blot test, and antistreptolysin O (ASLO) titer.
K.Suspected mononucleosis: Heterophile antibody test.
L.Suspected Salmonella: Widal’s test.
M.Suspected thyroiditis: Thyroid profile.
N.Suspected malaria or relapsing fever: Direct examination of blood smears.
O.Q-fever serology if risk factors include exposure to farm animals.
P.Imaging: Depends on suspected infection:
1.Chest, sinus radiographic films.
2.Gastrointestinal (GI) studies: Proctosigmoidoscopy, evaluation of gallbladder function.
3.CT scan of abdomen and pelvis, abdominal ultrasonography.
4.MRI is better than CT scan for detecting lesions of the nervous system.
Q.Suspected embolism: Ventilation-perfusion (V/Q) scan.
R.Suspected endocarditis or atrial myxoma: Echocardiography.
S.Radionuclide studies: Gallium scan and radium-labeled immunoglobulin useful in detecting infection and neoplasm.
T.Laparotomy in the deteriorating patient if the diagnosis is elusive despite extensive evaluation. Any abnormal finding should be aggressively evaluated: Headache necessitates a lumbar puncture to rule out meningitis; biopsy any skin from an area of rash to look for cutaneous manifestations of collagen vascular disease or infection. Enlarged lymph nodes should be aspirated or biopsied and examined for cytologic features to rule out neoplasm and send for culture.
Differential Diagnoses
Fever patterns can help the practitioner with diagnosis.
A.FUO.
B.Systemic and localized infections.
C.Neoplasms.
D.Autoimmune disorders.
E.Thrombophlebitis.
F.Miscellaneous causes (see Definition
earlier in this section).
G.Fever in patients older than 65 years:
1.Autoimmune disorders including temporal arteritis, rheumatoid arthritis, and polymyalgia rheumatica.
2.Infections including TB, infective endocarditis, intraabdominal abscesses, complicated urinary tract infections.
3.Malignancies especially hematological malignancies.
4.Drug-related fever.
Plan
A.General interventions:
1.Observe the patient taking own temperature to document the presence of a fever to make sure the temperature is not self-induced.
B.Patient teaching:
1.Instruct the patient to keep a record of temperatures, preferably rectal. At least morning and evening.
2.Reassure the patient that there is nothing abnormal about temperatures in the range of 97.0°F to 99.3°F.
3.Instruct the patient on use of physical cooling aids, such as cool towels or dampening clothing with tepid water.
4.Explain to the patient that immersion in an ice water bath may be indicated for hyperthermic emergencies.
5.Instruct patient on the importance of staying well hydrated. Increase fluid intake.
C.Pharmaceutical therapy:
1.Start therapeutic trials if a diagnosis is strongly suspected:
a.Antituberculous drugs for TB.
b.Tetracycline for brucellosis.
c.If the patient shows no clinical response in 2 weeks, stop therapy and reevaluate.
2.Symptomatic antipyretic therapy: Salicylates or acetaminophen every 4 hours if not contraindicated. nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can be also be used.
Follow-Up
A.Follow up in 24 to 48 hours.
B.Indications for admission to the hospital: Fever remains elevated beyond 101°F for weeks, and ambulatory diagnostic efforts have been unsuccessful.
Consultation/Referral
A.Consult with a physician for diagnosis and comanagement if indicated.
B.Refer the patient to a specialist if unable to differentiate definitive diagnosis.
Individual Considerations
A.Pregnancy:
1.Refer the patient for perinatal consultation.
2.High fevers early in the first trimester have been associated with an increase in neural tube defects.
3.Maternal fevers may cause fetal tachycardia.
B.Geriatric:
1.Common causes of FUO include TB, Hodgkin’s lymphoma, and temporal arteritis.
2.Elderly patients commonly present with nonspecific symptoms.
3.Elderly patients frequently present with altered mental status.
4.Elderly patients are at higher risk for developing dehydration with fever. Monitor closely monitoring for signs and symptoms of dehydration.
5.Review immunization status. Educate the patient on the importance of being immunized for pneumococcus (PVS13 and PPVS23) and influenza annually.
6.Geriatrics’ FUO must not be mistaken with end-of-life fever that often occurs during the final weeks or days of life. Although the origin is unknown research suggests it is due to infection, neoplasm, or neurologic injury. The first-line agents for treatments are acetaminophen and NSAIDs for comfort palliative measures.