By at least one definition, when a fever of more than 101°F (38.3°C) occurs on several occasions over three weeks without identification of its cause despite extensive investigation for at least a week, it becomes a fever of unknown origin (FUO). There are other definitions specific to institutional protocols, which include (a) 2 weeks of fever with either 3 days of inpatient assessment or 3 outpatient visits, and (b) fever on at least 4 occasions over a 2 week period and 2 weeks of illness. Difficult-to-diagnose fevers have several potential underlying causes, including infections, autoimmune diseases, and undiscovered cancers. Between 5% and 15% of FUOs remain undiagnosed.

To determine the underlying cause of a FUO, take careful note of the patient's history and symptoms. Recent travel to regions endemic for specific infections provides clues, as does a history of drinking contaminated water. The diagnostic path should include repeated physical examinations, laboratory evaluations, noninvasive methods such as sonography, and invasive diagnostic techniques such as biopsy.

The inability to diagnose FUO creates a dilemma regarding treatment. Experimental evidence suggests that elevated temperatures benefit patients by enhancing the body's defense mechanisms. However, clinical studies have not conclusively supported that position.

Treat fevers in children susceptible to febrile seizures. Also provide therapy to adults with cardiac or pulmonary conditions, as increases in body temperature reduce oxygen consumption.

Unknown by definition, but most probably due to infection, neoplasm, vascular disease, or other endocrine, occupational, or environmental causes. Provider must rely on patient's present and previous symptoms and diseases, current medications, exposure to infections, recent travel, and other diagnostic clues. Efforts to identify the cause of any fever start with the patient's medical history and move on through physical examination, blood tests, noninvasive diagnostic techniques, and invasive methods.

• Recent travel, especially overseas
• Exposure to malaria, which can cause fever every second or third day
• Exposure to certain fungi, such as coccidioidomycosis in the southwestern United States and histoplasmosis in the Ohio River and Mississippi River valleys
• Drinking contaminated water or consuming ice made from such water, which may indicate typhoid fever
• Working in a meat-packing plant, which can harbor brucellosis
• Use of medications that cause feverish adverse reactions
• Drug use or abuse
• AIDS

• Fever of more than 101°F (38.3°C), either continuous or intermittent, for at least two weeks
• Fever above 101°F whose identity remains unknown even after extensive diagnostic testing
• Accompanying headache, myalgia, and general malaise

There is a long list of potential causes, including the many forms of infection, neoplasms, vascular disease, endocrine disorders, and environmental or occupational insults.

Concentrate on the skin, eyes, nail beds, lymph nodes, heart, and abdomen to obtain the best clues to the fever's origin. Repeat the examinations frequently as the fever progresses undiagnosed. Take a thorough history. Inquire about exposure to malaria. Determine whether the patient's workplace might harbor infective agents. Check whether the patient has drunk contaminated water. Consider the possibility that a medication has caused the fever.

CBC for anemia, leukopenia, lymphocytosis, thrombocytosis. Liver function tests for obstructive diseases and inflammation. Blood cultures for aerobic or anaerobic pathogens. Other body fluids and tissue for bacteria, mycobacteria, and fungi. Urine analysis for infection or malignancy in urinary tract. Serology for CMV, infectious mononucleosis, HIV, toxoplasmosis, and chlamydia.

Dependent on etiology

Ultrasound can reveal the presence of cardiac vegetations, as well as abnormalities in the pancreas, liver, and gallbladder. Computed tomography and magnetic resonance imaging can help detect intra-abdominal abscesses, abnormalities in the lymph nodes, and pathology of the spleen, liver, kidneys, adrenals, pancreas, heart, mediastinum, or pelvis. Scanning with radionuclide tracers (especially gallium) may identify localized areas of infection or inflammation.

• Skin tests and sputum/urine cultures
• HIV antibody, thyroid, and rheumatoid factor tests
• Biopsy liver, bone marrow, or other suspected sites if other tests have failed to produce a definitive diagnosis.

Debate surrounds the issue of whether or not to treat fever, particularly when its source remains unknown. Advise rest, avoidance of rapid changes in ambient temperature, and drinking large amounts of fluids. Prescribe antipyretics for children who have suffered febrile seizures and adults with heart or lung insufficiencies, who can be endangered by the excess demand for oxygen brought on by the fever. Expect increased caloric and fluid demands. Also, treat patients with organic brain syndrome; fever can cause changes in their mental status. Wise treatment requires all possible efforts to identify the fever's origin.

Use appropriate antipyretics where necessary to control the fever:

• Acetaminophen
• Aspirin and other nonsteroidal anti-inflammatory drugs. Avoid prescribing aspirin for children and teenagers, because it increases the risk of Reye's syndrome.

If examination indicates the presence of infection, prescribe appropriate agents based on patient history. A wide variety of anti-infective drugs exists, tailored to specific types of infection. These include antibiotics, and antimicrobial, antifungal, and antiviral agents. Note that the drugs have less effect in patients with severely impaired immune systems. A steroid trial may be considered, although consider detrimental effects with certain undiagnosed conditions.

General immune support with nutrition and herbs may alleviate fevers of unknown origin. Homeopathic remedies may provide relief.

• Eliminate alcohol, caffeine, refined foods, and sugar which have an immunosuppressive effect.
• Water and/or electrolyte replacement drinks should be increased to prevent dehydration.
• Vitamin C (250 to 1,000 mg bid to tid), beta-carotene (15,000 to 50,000 IU/day), and zinc (10 to 30 mg/day) enhance immunity and reduce inflammation.

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, it is important to ascertain a diagnosis before pursuing treatment. Herbs may be used as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, teas should be made with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups/day. Tinctures may be used singly or in combination as noted.

The following antipyretic herbs and immune supportive herbs may be helpful in reducing fever and improving immunity: coneflower (Echinacea purpurea), yarrow (Achillea millefolium), white willow bark (Salix alba), lemon balm (Melissa officinalis), spearmint (Mentha spicata), catnip (Nepeta cateria), and elder (Sambucus nigra). Combine 1 part of coneflower and 1 part white willow bark with equal parts of 2 or more herbs. Drink 3 to 4 cups/day, 2 to 4 ounces tid to qid for children.

An experienced homeopath should assess individual constitutional types and severity of disease to select the correct remedy and potency. For acute prescribing use 3 to 5 pellets of a 12X to 30C remedy every one to four hours until acute symptoms resolve.

• Aconite when fever comes on suddenly and alternates with chills, heat, and flushing of the face. There is thirst for cold drinks, with anxiety.
• Apis mellifica for fever with alternating sweats and dry heat.
• Belladonna for sudden onset of high fever with hot, red face, glassy eyes, thirstlessness, and hot body with cold hands.
• Bryonia for fever with marked aggravation from the slightest movement.

Acupuncture may be helpful in supporting immune function.

Continue to examine patient and take blood for culturing until the cause of the fever becomes evident. A thoughtful, individualized approach to the patient eventually identifies the cause in most cases.

Caution with international travel and exposure to obvious contaminants will reduce likelihood of acquiring certain causative pathogens.

Dependent on etiology. Before any surgeries, patient should inform staff of history of fever of unknown origin.

Dependent on etiology, patient age, and other compromise

Left untreated, fever can be dangerous to the fetus. Nutritional, herbal, and homeopathic support for fevers are generally safe in pregnancy, yet use with caution.

Bartram T. Encyclopedia of Herbal Medicine. Dorset, England: Grace Publishers; 1995:182.

Berkow R. Merck Manual, Home Edition. Rahway, NJ: The Merck Publishing Group; 1997.

Berkow R, Beers MH. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: The Merck Publishing Group; 1992.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine. Boston, Mass: Integrative Medicine Communications; 1998:427.

Duke JA. The Green Pharmacy. Emmaus, Pa: Rodale Press, 1997.

Morrison R. Desktop Guide to Keynotes and Confirmatory Symptoms. Albany, Calif: Hahnemann Clinic Publishing; 1993:6, 58, 62.

Walker LP, Hodgson E. The Alternative Pharmacy. Paramus, NJ: Prentice Hall Press; 1996.