Eleanor Roosevelt was not only this nation's longest-serving first lady, holding the job from 1933 to 1945, she also transformed the office. She had her own staff, held her own news  conferences, wrote a newspaper column, and hosted a radio program. She traveled the nation and the world, first for her husband's programs, including the New Deal, and to speak out against American neutrality in the face of growing European fascism.

Though she had been a shy child and young woman, she learned to accept the spotlight in the 1920s, when paralysis nearly caused Franklin Roosevelt to leave politics. Until the end of his life, she frequently made appearances on his behalf, around the nation and abroad — and after his death she continued working for civil rights and women's rights at home and around the world.

President Harry Truman appointed her to the first U.S. delegation to the U.N. General Assembly from 1945-1952, and eventually drafted the Universal Declaration of Human Rights. Truman heralded her as the "First Lady of the World" for her humanitarian and diplomatic work throughout Europe, Asia, the Pacific and the Middle East.

By 1960, her focus had shifted to working on helping American inner cities. Then in her mid-70s, she started to experience some weakness and fatigue. A medical checkup discovered anemia, prompting two blood transfusions. While receiving blood, she suffered the first of many transfusion reactions, with a high fever and chills.  By April 1962, she had worsening anemia plus a low white blood cell count and low platelet count, a deficiency of three bone marrow products. She was referred to a hematologist for a bone marrow test.

Still feeling weak and fatigued, with persistent fevers,  in August Mrs. Roosevelt traveled to Campobello Island for the dedication of the Franklin Roosevelt Bridge, linking the family's Canadian island home to Maine. Six weeks later, on Sept. 26, 1962, she was back in  the hospital with persistent fever, sweating, a dry cough and blood in her stool, a sign of bleeding in her gastrointestinal tract. Doctors noted that her medical history included pleurisy back in 1919, when she was 35.

What was the cause of the aplastic anemia?   Could the combination of fever, cough, sweating and bleeding be connected to the anemia? Was it the reason for Mrs. Roosevelt's steady decline?

Solution:

The bone marrow test showed aplastic anemia, a rare disorder, characterized by decreased red and white blood cells, as well as platelets,  and risk of hemorrhage, infection, organ dysfunction — and high mortality. Her body wasn't making enough of the blood "stem cells" that give rise to all other blood cells, and the marrow was filled with fat. The cause, in her case, wasn't known, and that can still happen for some patients with the disease, whose known causes include viral infections, certain medications including chemotherapy, and toxic exposures.

Today, treatment for aplastic anemia consists of immunosuppressive drugs, combined  with corticosteroids and cyclosporin. Hematopoietic stem cell transplantation can be performed, especially for patients with a related matched marrow donor.

In Mrs. Roosevelt's case, prednisone, a synthetic adrenal corticosteroid, was started to stimulate the bone marrow to produce more blood cells. Her fever went down at first, but then went back up in a matter of days and continued to fluctuate. A negative effect of corticosteroids is to decrease patients' ability to fight infection.

Despite prednisone therapy, Mrs. Roosevelt continued to require blood transfusions in the summer of 1962; a post-transfusion fever of 105 degrees landed her back in the hospital.

Because of her cough, fever and sweats, tests were started for tuberculosis. On Sept. 27, 1962, a second bone marrow test was performed. Bacteria were not immediately detected, but doctors decided to start her on anti-tuberculosis medication — streptomycin and isoniazid — because the lab culture could take six  weeks to develop. They labeled her case a "fever of unknown origin."

Mrs. Roosevelt declared that she wasn't going to die in the hospital, and went home with her daughter Anna on Oct. 18, 1962. No definitive diagnosis had been made, but doctors noted her prognosis was poor.

On Nov. 4, she suffered an apparent stroke, and died on Nov. 7,  at age 78. American flags around the world flew at half-staff.

Two weeks before her death, the bone marrow culture was  announced positive for growth of mycobacterium tuberculosis. Her autopsy found TB infection in multiple organs, although without the granuloma inflammation that is more typical — and might have made her diagnosis more apparent. Her aplastic anemia — and the steroids used to treat it — likely contributed to her body's inability to fight off the TB infection.

How did she end up with TB? Doctors speculated that the pleurisy she contracted as a young woman could have reactivated.  They were perplexed, though, that Mrs. Roosevelt had not responded to six weeks of specific anti-tuberculosis therapy. But it turned out that the TB organisms in her body were found resistant to both the drugs that were used, causing suspicion that she contracted the disease in later years.

Allan B. Schwartz, M.D., is a professor of medicine in the Division of Nephrology & Hypertension at Drexel University College of Medicine.