Pellagra is a systemic disease caused by a deficiency in the B vitamin niacin (also known as vitamin B3 or nicotinic acid). However, it can also be brought about by poorly-balanced intake of amino acids. Pellagra is characterized by the classical symptoms of dermatitis, diarrhea and dementia.
In addition to obtaining a dietary history, low levels of urinary excretion of N-methyl nicotinamide and pyridone can be used to diagnose niacin deficiency and support the diagnosis of pellagra.
Treatment of pellagra consists primarily of exogenous replacement of niacin or nicotinamide. However, patients with pellagra are frequently deficient in other B vitamins too and are generally prescribed B vitamin complexes. Prescription of a balanced diet and replenishment of calories is also frequently required due to the fact that pellagra patients are generally malnourished.
The dermatitis component can be treated with emolients and topical corticosteroids. Treatment of concurrent conditions such as psychiatric disorders and malabsorption syndromes should also be undertaken.
Prognosis of pellagra is generally good if recognized and treated early with niacin supplementation. The dermatological and diarrheal symptoms of pellagra subside over a period of 2 weeks and the neurologic symptoms following thereafter. Untreated pellagra can result in death however, due to cardiomyopathy resulting from impairment of cellular metabolic functions.
Pellagra is caused by niacin deficiency. Niacin deficiency may occur as a result of poor dietary intake, as seen in areas corn is a staple food. Corn is deficient in niacin. However, niacin deficiency can occur as a result of deficiency in intake of its precursor molecule tryptophan. Hence, a diet poor in amino acid balance can also result in pellagra. Medical conditions in which a poor diet is a usual component, particularly anorexia nervosa and alcoholism, can manifest in pellagra.
Following on from this, excess metabolic demand for tryptophan can also cause pellagra as seen in carcinoid syndrome. Carcinoid syndrome, which is caused by excess serotonin production, diverts tryptophan towards the production of serotonin. Malabsorption disorders can also lead to pellagra due to inadequate absorption of amino acids. Hartnup disease, which is a congenital disorder of amino acid absorption, can also result in pellagra due to deficiency in tryptophan absorption.
Certain medications such as 5-fluoro-uracil, isoniazid, pyrazinamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol can also induce pellagra. These medications inhibit the biosynthesis of niacin by inhibiting the conversion of tryptophan to niacin.
Pellagra afflicts young adults commonly and affects both males and females equally. Historically, rural areas of the United States with high levels of poverty saw epidemic proportions of pellagra during the depression era. Although Central American cultures depend on corn as a staple, pellagra does not occur in Central America due to differences in preparation methods of the corn. Fortification of bread and flour with niacin occurred in 1941 making pellagra a rare entity in modern times. Nonetheless, pellagra remains a common entity in developing countries.
Niacin is the precursor for nicotinamide which in turn is the precursor for nicotinamide adenine dinucleotiode (NAD). NAD in its oxidized and reduced form are known as NAD+ and NADH respectively. These two molecules play a key role in electron transfer reactions such as oxidative phosphorylation. Hence a deficiency in niacin has widespread consequences on whole body cell metabolism thereby underlying the widespread systemic symptoms pellagra. The skin photosensitivity seen in pellagra is possibly due to an indirectly induced zinc deficiency. The depression seen in pellagra may be a result of serotonin deficiency.
Prevention of pellagra primarily depends on consumption of a balanced diet. Since 1941, flour and bread have been fortified in the United States with niacin which helped to virtually eliminate dietary-related pellagra in the United States. Primary prevention efforts are especially important in those who are at risk for poor nutrition – e.g. schizophrenics, anorexics, patients with Crohn disease or short gut syndrome. Such patients would benefit from a focus on dietary counseling and education.
Pellagra was initially described by Don Gaspar Casal in 1735 in Spanish peasants. The word "pellagra" is derived from the Latin words "pelle" - skin and "agra" - rough. Thereby describing one of the three cardinal symptoms of pellagra i.e. dermatitis, which is the most easily recognizable outward symptom of the disease. Historically, pellagra was initially recognized as caused by poor nutrition seen in poor populations living in regions where corn is the staple food. More recently, pellagra is recognized as a complication of poor nutrition secondary to other medical conditions such as alcoholism, eating disorders and schizophrenia.