Very little is more challenging to a doctor than a patient who has a high temperature with no apparent cause.

One such memorable patient dates back to my hospital training days in the early '60s, when a 77-year-old widow was admitted with an unexplained fever of six weeks’ duration. Her doctors, some of the most eminent of their time, were mystified by her prolonged fever.

Finally, at her insistence, that patient, Eleanor Roosevelt, was discharged to her New York City apartment, where she died weeks later. An autopsy showed that the cause of her high temperature was a rare, resistant form of tuberculosis. The fact that nothing could have saved her only partially eased the frustration those bedside luminaries felt for not having arrived at a diagnosis during her lifetime.

Measuring a High Temperature

Though Roosevelt’s persistent high temperature was caused by an uncommon illness, fever is a marker for so many disorders that it’s important to know when you are running one. Although chills, dry mouth, headache, malaise, or night sweats might make you suspect a fever, the only way to be sure is to measure your temperature with a thermometer. And the most convenient, practical way to do that in an adult is by mouth (rectal temps are usually 1 degree higher).

Although body temperature is never a static 98.6° F—it can vary by a degree or so during the course of a day—most experts would agree that an oral temp of 100° F or above constitutes an abnormal rise in body temperature. That goes for adults as well as children.

Should You Call the Doctor About a Fever?

Any fever that lasts for more than three days—especially without any of the aforementioned symptoms—merits a discussion with your doctor. It’s also prudent to consult a doctor about even a slight fever if you have diabetes, a heart valve disorder, or HIV or another disease that affects your immune system, or if you are taking a medication that can reduce immunity, such as prednisone.

If your infant of three months or younger has a fever of 100.4° F or higher, the American Academy of Pediatrics recommends that you call the doctor right away. (If you can't reach the doctor, take the baby to an urgent care facility or the emergency room.)

Children between 3 and 36 months should be evaluated if their fever reaches 102° F, or they have a fever of 100° F and appear ill—fussy or unwilling to drink fluids, for instance—or the fever lasts for three days. Children who have any fever and a new skin rash should also see a doctor.

When the Cause Is Unknown

High temperatures are most often caused by viral infections of limited duration or common bacterial infections such as bacterial pneumonia or urinary tract infections. But sometimes the cause is hard to pinpoint, as in Roosevelt’s so-called fever of unknown origin (FUO).

An FUO is best defined as at least two or three weeks of fever, intermittent or constant, without an evident cause. Even today, a formidable number of patients with FUOs (more than half, according to the most recent analysis) go undiagnosed. Fortunately, many get better.

In most studies, up to 20 percent of FUOs are caused by cancers. Notorious among the culprits are Hodgkin lymphoma and non-Hodgkin lymphoma. Other usual suspects that doctors consider include cancers of the bile duct, kidney, and liver.

About 20 percent of FUOs ultimately turn out to be uncommon infections such as subacute bacterial endocarditis, a heart valve infection that can be fatal if not diagnosed in time to be treated. (Some other previously hard-to-diagnose infections, such as abscesses of the liver or brain, are now more easily diagnosed.)

The identification of HIV/AIDS in the 1980s provided the key to the diagnosis of several previously rare infectious causes of FUO, such as cytomegalovirus, pneumocystis, and toxoplasmosis.

Diseases of connective tissue (the glue that holds our cells together), such as lupus or polyarteritis, can cause fever long before the appearance of symptoms such as joint pain or rash. The same can be said of inflammatory bowel diseases such as ulcerative colitis or regional ileitis.

Sometimes antibiotics, the very medications used to combat fever-causing infections, cause fever themselves. Those include sulfa drugs such as sulfamethoxazole/trimethoprim (Bactrim DS and generic) and nitrofurantoin (Macrodantin and generic), which treat urinary tract infections, and minocycline (Dynacin and generic), often used to treat acne rosacea.

And today, with only hours separating faraway countries from one another, a doctor should ask about the preceding six months of travel in any case of FUO. Malaria is still the No. 1 killer worldwide, and disease-causing organisms such as chikungunya, dengue, and Zika are always seeking openings in our health defenses, adding to the complexity of adequately identifying the cause of a fever in any given individual.

Editor's Note: This article was originally published in the April 2016 issue of Consumer Reports on Health.