Pellagra

Pellagra
Classification and external resources
Pellagra sufferer with skin lesions
ICD-10	E52
DiseasesDB	9730
MedlinePlus	000342
eMedicine	ped/1755
MeSH	C18.654.521.500.133.699.529

Pellagra is a vitamin deficiency disease most commonly caused by a chronic lack of niacin (vitamin B₃) in the diet. It can be caused by decreased intake of niacin or tryptophan,^[1] and possibly by excessive intake of leucine.^[2] It may also result from alterations in protein metabolism in disorders such as carcinoid syndrome. A deficiency of the amino acid lysine can lead to a deficiency of niacin as well.^[3]

History

The traditional food preparation method of corn (maize), 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.^[4] 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 Principality" (1762). This led to the disease being known as "Asturian leprosy", and it is recognized as the first modern pathological description of a syndrome.^[5] It was an endemic disease in northern Italy, where it was named "pelle agra" (pelle = skin; agra = sour) by Francesco Frapoli of Milan.^[6] 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, people also believed it was carried by insects. It was not until later that the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop (and is processed), was noted and the idea was considered that the causes of pellagra may be due to factors other than toxins.

Dr. Joseph Goldberger

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.^[7] 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 brewer's yeast^[8] prevented pellagra.

Goldberger performed an experiment using 11 volunteers from a prison, giving them clean clothes and keeping them in a house that was cleaned every day. Before the experiment, the prisoners were eating fruits and vegetables from the prison garden. Goldberger started feeding them only corn. About 2 weeks into the experiment the prisoners complained of headaches, confusion, and loss of appetite. In the third week, 7 of the 11 broke out in pellegra, and two prisoners begged for release. Goldberger cured them, feeding them fruits and vegetables again, and gave them their freedom. However, he failed to identify a specific element whose absence caused the pellagra. Goldberger continued his work but died of cancer without discovering the cause.

In 1937, Conrad Elvehjem PhD of Madison, Wisconsin showed 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.

In the research conducted between 1900 and 1950, it was found that the number of cases of women with pellagra was consistently double the number of cases of afflicted men.^[9] This is thought to be due to the inhibitory effect of estrogen on the conversion of the amino acid tryptophan to niacin.^[10] It is also thought to be due to the differential and unequal access to quality foods within the household. Some researchers of the time gave a few explanations regarding the difference.^[11] As primary wage earners, men were given consideration and preference at the dinner table. They also had pocket money to buy food outside the household. Women gave quality protein foods to their children first. Women also would eat after everyone else had a chance to eat.^{[citation needed]}

Gillman and Gillman related skeletal tissue and pellagra in their research in South African Blacks. They provide some of the best evidence for skeletal manifestations of pellagra and the reaction of bone in malnutrition. They claimed radiological studies of adult pellagrins demonstrated marked osteoporosis. A negative mineral balance in pellagrins was noted which indicated active mobilization and excretion of endogenous mineral substances, and undoubtedly impacted the turnover of bone. Extensive dental caries were present in over half of pellagra patients. In most cases caries were associated with "severe gingival retraction, sepsis, exposure of cementum, and loosening of teeth".^[12] Pellegra is no longer common in the United States, as niacin is now a required addition to certain foods.^{[citation needed]}

Epidemiology

Pellagra can be common in people who obtain most of their food energy from maize (often called "corn"), notably rural South America where maize is a staple food. If maize is not nixtamalized, it is a poor source of tryptophan as well as niacin. Nixtamalization of the corn corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, like Mississippi and Alabama, as well as among the inmates of jails and orphanages as studied by Dr. Joseph Goldberger.

Pellagra is common in Africa, Indonesia, and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol-dependent, or psychiatric patients who refuse food.^[13] Pellagra was common among prisoners of Soviet labor camps, the Gulag. It can be found in cases of chronic alcoholism. In addition, pellagra is a micronutrient deficiency disease that frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely on limited sources of niacin provided to them, such as groundnuts; the instability in the nutritional content and distribution of food aid can be the cause of pellagra in displaced populations.

Symptoms

The dermatologic features of this disorder include desquamation, erythema, scaling, and keratosis of sun-exposed areas, all of which this patient had.

Pellagra is classically described by "the four D's": diarrhea, dermatitis, dementia and death.^[14] A more comprehensive list of symptoms includes:

• High sensitivity to sunlight
• Aggression
• Dermatitis, alopecia, oedema
• Smooth, beefy red glossitis
• Red skin lesions
• Insomnia
• Weakness
• Mental confusion
• Ataxia, paralysis of extremities, peripheral neuritis
• Diarrhea
• Dilated cardiomyopathy
• Eventually dementia

Frostig and Spies (acc. to Cleary and Cleary) described more specific psychological symptoms of pellagra as:^[15]

• Psycho-sensory disturbances (impressions as being painful, annoying bright lights, odours intolerance causing nausea and vomiting, dizziness after sudden movements)

• Psycho-motor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action)

• Emotional disturbances

Pathophysiology

Pellagra can develop according to several mechanisms, all of which ultimately revolve around niacin deficiency. The first is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan,^[1] an essential amino acid found in soybeans, meat, poultry, fish, and eggs^[16] that the body converts into niacin. Third, it may be caused by excess leucine, though the relationship is unclear.^[2]

Alterations in protein metabolism may also produce pellagra-like symptoms. An example of this is carcinoid syndrome, a disease in which carcinoid tumors produce excessive serotonin. 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 percent. The diversion of tryptophan to making serotonin in patients with metastatic tumors can result in tryptophan deficiency. Carcinoid syndrome thus may produce decreased protein synthesis, niacin deficiency, and clinical manifestations of pellagra.

Prognosis

Untreated, the disease can kill within four or five years. Treatment is with nicotinamide, a chemical related to niacin. The frequency and amount of nicotinamide administered depends on the degree to which the condition has progressed.

See also

• Hartnup disease
• Central chromatolysis

References

1. ^ ^{a b} Pitche P (2005). "Pellagra". Sante 15 (3): 205–8. PMID 16207585. 
2. ^ ^{a b} 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. 
3. ^ http://www.vitamins-supplements.org/amino-acids/lysine.php
4. ^ Rajakumar, K (2000). "Pellagra in the United States: A Historical Perspective". Southern Medical Journal 98 (3): 272–277. ISSN 00384348. PMID 10728513. 
5. ^ Stratigos JD, Katsambas A (1977). "Pellagra: a still existing disease". Br. J. Dermatol. 96 (1): 99–106. doi:10.1111/j.1365-2133.1977.tb05197.x. PMID 843444. 
6. ^ "Definition of Pellagra". MedicineNet.com. http://www.medterms.com/script/main/art.asp?articlekey=4821. Retrieved 2007-06-18. 
7. ^ 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. PMC 2589605. PMID 1285449. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2589605. 
8. ^ Swan, Patricia (2005). "Goldberger's War: The Life and Work of a Public Health Crusader (review)". Bulletin of the History of Medicine (The Johns Hopkins University Press) 79 (1): 146–7. doi:10.1353/bhm.2005.0046. http://muse.jhu.edu/journals/bulletin_of_the_history_of_medicine/v079/79.1swan.html. 
9. ^ Miller DF (1978). "Pellagra deaths in the United States". Am. J. Clin. Nutr. 31 (4): 558–9. PMID 637029. 
10. ^ Brenton, Barrett (2000). "Pellagra, Sex and Gender: Biocultural Perspectives on Differential Diets and Healths". Nutritional Anthropology 23 (1): 20–24. doi:10.1525/nua.2000.23.1.20. 
11. ^ Carpenter, Kenneth (1981). Pellagra. Stroudsburg, Pa: Hutchinson Ross Pub. Co. ISBN 0-87933-364-2. 
12. ^ Gillman, Joseph; Gillman, Theodore (1951). Perspectives in Human Malnutrition: A Contribution to the Biology of Disease from a Clinical and Pathological Study of Chronic Malnutrition and Pellagra in the African. New York, New York: Grune and Stratton. 
13. ^ Jagielska G, Tomaszewicz-Libudzic EC, Brzozowska A (2007). "Pellagra: a rare complication of anorexia nervosa". Eur Child Adolesc Psychiatry 16 (7): 417–20. doi:10.1007/s00787-007-0613-4. PMID 17712518. 
14. ^ Hegyi J, Schwartz R, Hegyi V (2004). "Pellagra: dermatitis, dementia, and diarrhea". Int J Dermatol 43 (1): 1–5. doi:10.1111/j.1365-4632.2004.01959.x. PMID 14693013. 
15. ^ Cleary MJ, Cleary JP (1989). "Anorexia nervosa: a form of subclinical pellagra". Int Clin Nutr Rev 9: 137–143. ISSN 0813-9008. 
16. ^ Haas EM. "Vitamin B3—Niacin". Excepted from: Staying Healthy with Nutrition: The Complete Guide to Diet and Nutritional Medicine. http://www.healthy.net/scr/article.asp?ID=2125. Retrieved 2007-06-18. 

Further reading

• Hampl JS, Hampl WS (1 November 1997). "Pellagra and the origin of a myth: evidence from European literature and folklore". J Roy Soc Med. 90 (11): 636–9. PMC 1296679. PMID 9496281. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1296679. 
• "Reports and Resolutions of the General Assembly of the State of South Carolina, Regular Session Commencing January 11, 1916". Annual Report of the State Board of Health (1915-1916). (Columbia, S.C.: Gonzales and Bryan, state printers) 4. 1916. 
• Beardsley E (2006). The Spartanburg Pellagra Hospital. In: The South Carolina Encyclopedia. Columbia, S.C: University of South Carolina Press. ISBN 1-57003-598-9. 
• Swain CP, Tavill AS, Neale G (September 1976). "Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia". Gastroenterology 71 (3): 484–9. PMID 133045. 
• Hendrick, Burton J. (April 1916). "The Mastery Of Pellagra: The Mysterious Disease, Almost Unknown In This Country Fifteen Years Ago, That Now Claims 7,500 Victims A Year And Is Spreading Rapidly". The World's Work: A History of Our Time XXXI: 633–639. http://books.google.com/?id=09_Sr9emceQC&pg=PA633. Retrieved 2009-08-04. 

• Kraut, Alan. "Dr. Joseph Goldberger and the War on Pellagra, By Alan Kraut, Ph.D." Office of History, National Institutes of Health. Web. 03 Sept. 2010. <http://history.nih.gov/exhibits/goldberger/docs/pellegra_5.htm>.

External links

• wholegrain.umn.edu
• Pellagra