Signs and Symptoms

• Fever of more than 101°F (38.3°C), either continuous or intermittent, for at least 3 weeks
• Fever above 101°F (38.3°C) with no known cause, even after extensive diagnostic testing

What Causes It?

Fever is a symptom of more than 200 conditions. In children, infection accounts for about 50% of cases of fever of unknown origin, while inflammatory and malignant disease account for 5 to 10%. In adults, infections only account for 16% of cases, followed by tumors and noninfectious inflammatory diseases, such as rheumatoid arthritis. However, in up to half of cases in adults, no cause is found. Doctors can use a series of tests to narrow down the list of possible reasons for a high temperature.

What to Expect at Your Doctor's Office

A health care provider trying to diagnose the cause of a fever of unknown origin must look for every possible clue. The provider may ask you questions about:

• Your work, because some workplaces contain organisms that can cause fever.
• Places you have visited recently. Locations overseas, and even areas in the United States, can harbor diseases that can cause fever.
• Your exposure to pets and other animals.
• Your family history for possible hereditary causes of fever, for example, familial Mediterranean fever.

Your provider will also examine you closely, paying particular attention to your skin, eyes, nails, lymph nodes, heart, and abdomen. The provider will also take blood and urine samples. You may have an ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), and Positron Emission Tomography (PET). If the cause of the fever is still unknown, your provider may want to inject you with "labeled white blood cells." These are white blood cells that contain a harmless radioactive compound. Once injected, the white blood cells travel to infected parts of your body. The radioactivity allows your provider to see on an x-ray where the cells have moved. This may show the location of the infection responsible for your fever. If that test shows no results, your provider may want to perform minor surgery to take biopsy samples of, for example, your liver or bone marrow.

Treatment Options

Your doctor will advise you to rest and drink plenty of fluids. You may be asked to stop taking medications for other ailments, because those medications may be causing your fever. If you have a heart or lung problem, or in the case of a child who has seizures as a result of fever, your doctor will probably prescribe over-the-counter remedies to bring the temperature down.

Drug Therapies

• Acetaminophen (Tylenol)
• Aspirin and other nonsteroidal anti-inflammatory drugs. Avoid aspirin in children and teenagers. Reye syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver. It is associated with aspirin consumption by children with viral diseases, such as chicken pox.
• In cases of infection, your doctor may also prescribe an antibiotic, antifungal, or antiviral drug, depending on the cause of the infection.

Complementary and Alternative Therapies

General immune support with nutrition and herbs may alleviate fevers. Most natural medicine practitioners will treat fever as a sign that the body is trying to heal itself, rather than as an illness. In addition, most natural therapies attempt to support the body's own healing processes rather than suppress the fever. It is important to speak to your medical doctor about any natural therapies you may be considering. Prolonged fever can be dangerous, and some natural therapies and conventional medications can have dangerous interactions. If you are pregnant, or thinking of becoming pregnant, do not use any complementary and alternative therapies (CAM) unless directed to do so by your physician.

Nutrition and Supplements

These nutritional tips may help improve immunity:

• Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).
• Avoid refined foods, such as white breads, pastas, and sugar.
• Eat fewer red meats and more lean meats, cold-water fish, tofu (soy) or beans for protein.
• Use healthy cooking oils, such as olive oil or coconut oil.
• Reduce or eliminate trans-fatty acids, found in commercially baked goods, such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
• Avoid coffee and other stimulants, alcohol, and tobacco.
• Drink 6 to 8 glasses of filtered water daily.
• Exercise at least 30 minutes daily, 5 days a week. While experiencing intermittent fevers, your doctor may suggest mostly rest and some gentle stretching rather than your typical exercise regimen.

You may address nutritional deficiencies with the following supplements:

• A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
• Omega-3 fatty acids , such as fish oil, to help reduce inflammation. Omega-3 fatty acids may increase the effect of blood-thinning medications, such as warfarin (Coumadin). Speak with your physician.
• Acidophilus ( Lactobacillus acidophilus ), for maintenance of gastrointestinal and immune health. Some acidophilus products may need refrigeration -- read the label carefully. People who are severely immune compromised, or who are taking immune suppressive drugs, should speak to their doctors before taking probiotic supplements.
• Vitamin C , as an antioxidant.

Herbs

Herbs are a way to strengthen and tone the body's systems. As with any therapy, you should work with your doctor to choose the safest, most effective herbal therapies before starting treatment. You may use herbs as dried extracts (capsules, powders, or teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, make teas 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 per day. You may use tinctures alone or in combination as noted.

The following herbs may help reduce fever and improve immune response:

• Green tea ( Camelia sinensis ). To improve your immunity. You may also prepare teas from the leaf of this herb. Green tea may increase anxiety and blood pressure. It may also worsen diarrhea, glaucoma, and osteoporosis. People who have liver disease should consult their doctors before taking green tea.
• Cat's claw ( Uncaria tomentosa ). To improve immunity. Cat's calw may worsen certain conditions, such as leukemia or some autoimmune disorders. It can also potentially interfere with a variety of medications. Talk to your doctor.
• Reishi mushroom ( Ganoderma lucidum ). To improve your immunity. You may also take a tincture of this mushroom extract. Reishi can potentially interact with certain medications, including medicines for blood pressure and blood-thinning medicines, such as warfarin (Coumadin).
• Milk thistle ( Silybum marianum ). For detoxification support. Milk thistle may exert a hormone-like effect. People with a history of hormone-sensitive conditions should take caution when using milk thistle. It may also interact with many medications.
• Andrographis ( Andrographis paniculata ). Often used to treat colds and sore throats and may also help reduce a fever in Traditional Chinese Medicine. One clinical study suggested 6 g a day for 7 days was effective with no side effects. DO NOT use andrographis if you have gallbladder disease, an autoimmune disease, or if you are pregnant or trying to become pregnant. Andrographis can potentially interact with certain medications, including blood pressure medications and blood-thinning medications, such as warfarin (Coumadin).

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of fevers based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type, includes your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

• Aconitum . For fever that comes on suddenly and alternates with chills, heat, and flushing of the face. You may be anxious and crave cold drinks.
• Apis mellifica . For fever associated with alternating bouts of wet (sweating) and dry body heat.
• Belladonna . For sudden onset of high fever with hot, red face, glassy eyes, lack of thirst, and hot body with cold hands.
• Bryonia . For fever with symptoms that are aggravated by the slightest movement.
• Ferrum phosphoricum . For the first stages of a fever with a slow onset. This remedy is generally used if Belladonna is ineffective.
• Gelsemium . For fever accompanied by drowsiness and lack of thirst.

Physical Medicine

• Constitutional hydrotherapy. Involves the application of hot and cold packs to the body by a trained professional to evoke a general healing response by the body. With any hydrotherapy technique, it is crucial to avoid becoming chilled. All treatments should end with a vigorous rubdown.
• Wet socks treatment. This hydrotherapy technique can be done at home. Before going to bed, soak a pair of thin cotton socks with room temperature water and then wring them out so they are damp but not dripping wet. Put them on your feet, and put on a pair of dry thick socks (preferably wool) over them. Wear these to bed. As you sleep, your body will send blood and lymphatic fluid circulating in order to fight off the wetness on your feet. This stimulates the immune system and puts the body in a parasympathetic state that supports healing and restful sleep. By morning the socks should be completely dry. This technique can be done for 5 to 6 nights in a row. Then take 2 nights off and continue.
• Lukewarm baths. Sponging or bathing in lukewarm water can cool the skin and reduce body temperature. DO NOT use ice water or alcohol sponge baths.

Acupuncture

Acupuncture may help support immune function.

Special Considerations

Fever can be dangerous if you are pregnant. Speak with your physician.

Supporting Research

Belhassen-Garcia M, Velasco-Tirado V, Lopez-Bernus A, et al. Fever of unknown origin as the first manifestation of colonic pathology. Clin Med . 2013;13(2):141-5.

Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases . 7th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2009.

Bleeker-Rovers CP, van der Meer JW. Diagnostic approach to fever of unknown origin. Ned Tijdschr Geneeskd . 2008;152(15):869-73.

Bleeker-Rovers CP, van der Meer JW, Oyen WJ. Fever of unknown origin. Semin Nucl Med . 2009;39(2):81-7

Bryan CS, Ahuja D. Fever of unknown origin: is there a role for empiric therapy? Infect Dis Clin North Am . 2007;21(4):1213-20.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea -- a review. J Am Coll Nutr . 2006;25(2):79-99.

Chen Y, Zheng M, Hu X, et al. Fever of unknown origin in elderly people: a retrospective study of 87 patients in China. J Am Geriatr Soc . 2008;56(1):182-4.

Cunha BA. Fever of unknown origin: clinical overview of classic and current concepts. Infect Dis Clin North Am . 2007;21(4):867-915.

Diogo M. Adult-onset still disease as the cause of fever of unknown origin. Acta Med Port . 2010;23(5):927-30.

Gonclaves C, Dinis T, Batista MT. Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity. Phytochemistry . 2005;66(1):89-98.

Holder BM. Fever of unknown origin: an evidence-based approach. Nurse Pract . 2011;36(8):46-52.

Jun-Cai TU, Ping Z, Xiao-Juan LI, et al. Clinical Etiologies of Fever of Unknown Origin in 500 cases. Zhongguo Yi Xue Ke Xue Yuan Xue Bao . 2015;37(3):348-51.

Keidar Z, Gurman-Balbir A, Gaitini D, et al. Fever of unknown origin: the role of 18F-FDG PET/CT. J Nucl Med . 2008;49(12):1980-5.

Knockaert DC. Recurrent fevers of unknown origin. Infect Dis Clin North Am . 2007;21(4):1189-211.

Norman DC, Wong MB, Yoshikawa TT. Fever of unknown origin in older persons. Infect Dis Clin North Am . 2007;21(4):937-45.

Petelin A, Johnson DH, Cunha BA. Fever of unknown origin (FUO) due to systemic lupus erythematosus (SLE) presenting as pericarditis. Heart Lung . 2013;42(2):152-3.

Rigante D, Esposito S. A roadmap for fever of unknown origin in children. Int J Immunopathol Pharmacol . 2013;26(2):315-26.

Ritz N. Fever without focus and fever of unknown origin in childhood. Praxis . 2013;102(3):157-64.

Seashore CJ. Fever of unknown origin in children. Peditr Ann . 2011;40(1):26-30.

Tolia J, Smith LG. Fever of unknown origin: historical and physical clues to making the diagnosis. Infect Dis Clin North Am . 2007;21(4):917-36.

Turkulov V. Fever of unknown origin in elderly patients. Srp Arh Celok Lek . 2011;139(1-2):64-8.

Vertenoeil G, Servais S, Beguin Y. How to explore a fever of unknown origin in adult patients? Rev Med Liege . 2012;67(7-8);391-7.

Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J . 2005;46(5):585-96.