Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths, yet the epidemic resolved itself right after dietary niacin fortification. Pellagra deaths in South Carolina numbered 1,306 during the first ten months of 1915; 100,000 Southerners were affected in 1916. At this time, the scientific community held that pellagra was probably caused by a germ or some unknown toxin in corn. The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the nations first facility dedicated to discovering the cause of pellagra. It was established in 1914 with a special Congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research. In 1915, Dr. Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed it was linked to diet by observing the outbreaks of pellagra in orphanages and mental hospitals. Goldberger noted that children between the ages of 6 and 12 (but not older or younger children at the orphanages) and patients at the mental hospitals (but not doctors or nurses) were the ones who seemed most susceptible to pellagra. Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra. By modifying the diet served in these institutions with "a marked increase in the fresh animal and the leguminous protein foods," Goldberger was able to show that pellagra could be prevented. By 1926, Goldberger established that a diet that included these foods, or a small amount of brewers yeast, prevented pellagra.
Gastroenterostomy can also cause pellagra. Chronic alcoholism can also cause poor absorption which combines with a diet already low in niacin and tryptophan to produce pellagra. Hartnup disease is a genetic disorder that reduces tryptophan absorption, leading to pellagra. Alterations in protein metabolism may also produce pellagra-like symptoms. An example is carcinoid syndrome, a disease in which neuroendocrine tumors along the GI tract use tryptophan as the source for serotonin production, which limits the available tryptophan for niacin synthesis. In normal patients, only one percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this value may increase to 70%. Carcinoid syndrome thus may produce niacin deficiency and clinical manifestations of pellagra. Anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction. Several therapeutic drugs can provoke pellagra. These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis, and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine. Treatment
If untreated, pellagra can kill within four or five years. Treatment is with nicotinamide, which has the same vitamin function as niacin and a similar chemical structure, but has lower toxicity. The frequency and amount of nicotinamide administered depends on the degree to which the condition has progressed. Epidemiology
Pellagra can be common in people who obtain most of their food energy from corn, notably rural South America, where maize is a staple food.