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Pellagra is a vitamin deficiency disease caused by dietary lack of niacin (vitamin B3) and protein, especially proteins containing the essential amino acid tryptophan.[1] Because tryptophan can be converted into niacin, foods with tryptophan but without niacin, such as milk, prevent pellagra. However, if dietary tryptophan is diverted into protein production, niacin deficiency may still result.

Tryptophan is an essential amino acid found in meat, poultry, fish, and eggs. If your diet contains these foods, your need for niacin from other sources will be reduced.[2]

The relationship between lysine and pellagra is unclear.[3]

Historical Perspective

Portrait of Dr. Joseph Goldberger

The traditional food preparation method of corn, nixtamalization, by native New World cultivators, who had domesticated corn, required treatment of the grain with lime, an alkali. It has now been shown that the lime treatment makes niacin nutritionally available and reduces the chance of developing pellagra. When corn cultivation was adopted worldwide, this preparation method was not accepted because the benefit was not understood. The original cultivators, often heavily dependent on corn, did not suffer from pellagra. Pellagra became common only when corn became a staple that was eaten without the traditional treatment.

Pellagra was first described in Spain in 1735 by Gaspar Casal, who published a first clinical description in his posthumous "Natural and Medical History of the Asturian Pricipality" (1762). This led to the disease being knownn as "Asturian leprosy", and it is recognised as the first modern pathological description of a syndrome(1). It was an endemic disease in northern Italy, where it was named "pelle agra" (pelle = skin; agra = rough) by Francesco Frapoli of Milan.[4] Because pellagra outbreaks occurred in regions where maize was a dominant food crop, the belief for centuries was that the maize either carried a toxic substance or was a carrier of disease. It was not until later that the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop (and is processed), that the idea was considered that the causes of pellagra may be due to factors other than toxins.

In the early 1900s, pellagra reached epidemic proportions in the American South. There were 1,306 reported pellagra deaths in South Carolina 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.[5] The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the nation's 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 Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed that pellagra was linked to diet by inducing the disease in prisoners, using the Spartanburg Pellagra Hospital as his clinic. By 1926, Goldberger established that a balanced diet or a small amount of baker's yeast prevented pellagra. Skepticism still persisted in the medical community until 1937 when Conrad Elvehjem showed that the vitamin niacin cured pellagra (manifested as black tongue) in dogs. Later studies by Tom Spies, Marion Blankenhorn and Clark Cooper established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men of the Year in comprehensive science.




Drug Causes

Differentiating Pellagra from Other Diseases

Epidemiology and Demographics

Pellagra can be common in people who obtain most of their food energy from maize, since untreated corn is a poor source of niacin (vitamin B3). Corn is also a poor source of tryptophan. This disease can be common among people who live in rural South America where corn is a staplea. The symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. It is also one of several diseases of malnutrition common in Africa, and was endemic in the poorer states of the U.S. south like Mississippi and Alabama as well as among the inmates of jails and orphanages, where it was studied by Joseph Goldberger who conducted experiments in the penal colony in Rankin. Alkali treatment of the corn corrects the niacin deficiency, and was a common practice in native American cultures that grew corn. The amino acid deficiency must be balanced by consumption of other sources of protein. It was also common amongst prisoners of Soviet labor camps, the infamous Gulag. Also found in cases of chronic alcoholism.

Risk Factors


Natural History, Complications, and Prognosis

Natural History




Diagnostic Criteria

History and Symptoms


The symptoms of pellagra include:

The main results of pellagra can easily be remembered as "the four D's": diarrhea, dermatitis, dementia, and death.[6]

Physical Examination

Physical Examination



Laboratory Findings

Imaging Findings

Other Diagnostic Studies


Medical Therapy




  1. Pitche P (2005). "Pellagra". Sante. 15 (3): 205–8. PMID 16207585.
  2. Haas EM. "Vitamin B3—Niacin". Excepted from: Staying Healthy with Nutrition: The Complete Guide to Diet and Nutritional Medicine. Retrieved 2007-06-18.
  3. Bapurao S, Krishnaswamy K (1978). "Vitamin B6 nutritional status of pellagrins and their leucine tolerance". Am J Clin Nutr. 31 (5): 819–24. PMID 206127.
  4. "Definition of Pellagra". Retrieved 2007-06-18.
  5. Bollet A (1992). "Politics and pellagra: the epidemic of pellagra in the U.S. in the early twentieth century". Yale J Biol Med. 65 (3): 211–21. PMID 1285449.
  6. Hegyi J, Schwartz R, Hegyi V (2004). "Pellagra: dermatitis, dementia, and diarrhea". Int J Dermatol. 43 (1): 1–5. PMID 14693013.
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20 7.21 7.22 7.23 7.24 7.25 7.26 7.27 7.28 7.29 7.30 7.31 7.32 7.33 7.34 7.35 7.36 7.37 7.38 7.39 7.40 7.41 7.42 7.43 7.44 7.45 7.46 7.47 7.48 7.49 7.50 7.51 7.52 7.53 7.54 7.55 7.56 7.57 7.58 7.59 7.60 7.61 "Dermatology Atlas".

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