By Medifit Biologicals


Pellagra 1


Pellagra: A disease due to deficiency of niacin, a B-complex vitamin. Pellagra is the “disease of the four D’s” —

  • Diarrhea;
  • Dermatitis: A scaly rash on skin exposed to light or trauma;
  • Dementia: Mental disorientation, delusions and depression; and
  • Death.

Other features are ulcerations within the mouth (glossitis), nausea. vomiting, seizures and balance disorder (ataxia).

Pellagra is now rare in developed countries which enjoy balanced diets and fortified foods, but it was once a huge public health problem in the US. Three million Americans contracted pellagra and 100,000 died of it from 1906-40. Pellagra was especially a problem for the poor in the South whose meals usually consisted of the “three M’s”: meat (pork fatback); molasses; and meal (cornmeal). Today pellagra continues to be a problem in developing countries where there is significant malnutrition or where niacin-deficient foods such as corn and rice are the primary sources of nutrition.


In the 1800s, pellagra was common among poor Americans whose diets consisted mostly of corn, molasses, and salt pork — all poor sources of niacin. Today, most people in the developed world get plenty of niacin in their diets. Niacin deficiency is more likely to be caused by problems that affect absorption of niacin or tryptophan. The most common cause is alcoholism. Other possible causes include disorders of the digestive system and prolonged treatment with the tuberculosis drug isoniazid (Laniazid, Nydrazid).


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Pellagra is the late stage of severe niacin deficiency. Niacin, or vitamin B-3, is a water-soluble vitamin. In 1926, Goldberger reported that nicotinamide was a preventive factor of pellagra.

Pellagra can be divided into primary and secondary forms. Primary pellagra results from inadequate nicotinic acid (ie, niacin) and/or tryptophan in the diet (long-term parenteral nutrition without appropriate niacin substitution; anorexia nervosa; a self-imposed restriction diet in adult atopics with sensitizations to multiple foodstuffs). Niacin is a pyridine carboxylic acid that is converted into an amide in the body.

Niacin is required for adequate cellular function and metabolism as an essential component in coenzyme I (oxidized form of nicotinamide adenine dinucleotide [NAD]) and coenzyme II (reduced form of nicotinamide adenine dinucleotide phosphate [NADP]), which either donate or accept hydrogen ions in vital oxidation-reduction reactions. These compounds are important coenzymes for glycolysis, protein and amino acid metabolism, pyruvate metabolism, pentose biosynthesis, high-energy phosphate bond generation, glycerol metabolism, and fatty acid metabolism.

Nicotinamide has an in vitro down-regulatory effect on proinflammatory cytokines interleukin (IL)–1beta, IL-6, IL-8, IL-12, and tumor necrosis factor-alpha in a dose-dependent manner. Furthermore, it induces activation of tumor necrosis factor cachectin–induced macrophages and inhibits the expression of intercellular adhesion molecule 1 and major histocompatibility complex II. . Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis, mast cell histamine release, and antigen-induced lymphocyte transformation. It is able to scavenge oxygen radicals and to inhibit nitric oxide synthase mRNA induction in activated macrophages. Nicotinamide increases biosynthesis of ceramides, which, upon degradation, produce sphingosine. This inhibits protein kinase C and decreases basal cell proliferation.

This immunomodulatory and anti-inflammatory effect of nicotinamide in vitro may have great potential for the treatment of human inflammatory diseases by inhibition of neutrophil chemotaxis and secretion of inflammatory cytokines, suppression of lymphocyte transformation, and inhibition of mast cell histamine release and blockade of histamine receptors. Beneficial effects of topically applied nicotinamide in aging skin, such as improvement in barrier functions in atopic dry skin and decreased appearance of signs of facial photoaging (eg, skin texture changes and hyperpigmentation), have been noted. Nicotinic acid can be formed from dietary tryptophan. Maize contains appreciable amounts of niacin, but this niacin is present in a bound form. Treating corn used for dietary staples (eg, tortillas) with lime results in the release of bound niacin.

Pellagra 2

Because cellular functions in multiple organs and tissues are affected by niacin deficiency, the clinical expressions of pellagra are diverse. Pathologic changes in the skin include vascular dilatation, proliferation of the endothelial lining, perivascular lymphocytic infiltration, hyperkeratinization, and subsequent atrophy of the epidermis. Mucosal inflammation and atrophy involve most of the GI tract. Evidence of glossitis and atrophy of the papillae of the tongue are characteristic findings, along with gastritis and subsequent gastric mucosal atrophy. Acute inflammation of the small intestine and colon are also commonly noted. Pathologic changes in the nervous system can be found in the brain, spinal cord, and peripheral nerves. Findings include patchy demyelinization and degeneration of the affected parts of the nervous system.

Secondary pellagra occurs when adequate quantities of niacin are present in the diet, but other diseases or conditions interfere with niacin absorption and/or processing. Examples of these conditions include prolonged diarrhea; chronic alcoholism; chronic dialysis treatment; chronic colitis, particularly ulcerative colitis or regional enteritis; cirrhosis of the liver; tuberculosis of the GI tract; malignant carcinoid tumor; and Hartnup syndrome. Alcoholism can be considered a risk factor for pellagra, which can, as well, be considered an alcoholism indicator. Clinical manifestations of pellagra are a less sensitive indicator than biochemical niacin deficiency in carcinoid patients with carcinoid syndrome. Occasionally, an abortive form called pellagroid (eg, erythema pellagroids, pseudopellagra) is present. Hartnup syndrome is an inborn error of tryptophan metabolism.

In addition, the use of isoniazid is known to cause the symptoms of pellagra, as does the long-term administration of 5-fluorouracil. Isoniazid biochemically competes with niacin. Pellagra was also noted as a cutaneous adverse reaction after consumption of Kombucha tea.

Pellagra can develop in atopic dermatitis patients following elimination diets. It is important to consider that there is some crossover of the clinical and histological features with pellagra and necrolytic migratory erythema.


Symptoms of mild niacin deficiency include:

  • Indigestion
  • Fatigue
  • Canker sores
  • Vomiting
  • Depression

Severe deficiency, called pellagra, can cause symptoms related to the skin, digestive system, and nervous system. They include:

  • Thick, scaly pigmented rash on skin exposed to sunlight
  • Swollen mouth and bright red tongue
  • Vomiting and diarrhea
  • Headache
  • Apathy
  • Fatigue
  • Depression
  • Disorientation
  • Memory loss

If not treated, pellagra can lead to death.

Pelagra: estudio clínico, histopatológico y epidemiológico de 7 casos



Actinic reticuloid

Concomitant zinc deficiency

Pellagrous vulvitis

Pellagrous vaginitis

Pellagrous scrotal dermatitis

Contact dermatitis

Pyridoxine deficiency

Riboflavin deficiency

Vitamin B-12 deficiency

Drug eruptions – Distinguished by the drug history, clinical picture, localization, configuration, development of skin symptoms, and evidence of exposure to drug allergens

Dermatitis solaris – Distinguished by the history, clinical picture, monomorphism, localization, exposed sites, development of skin symptoms, lack of marked pigmentation, and fast healing

Eczema solare – Distinguished by the history, clinical picture, polymorphism, development of skin symptoms, lack of marked pigmentation, and itching

Eczema – Distinguished by the clinical picture, localization, development of skin symptoms, lack of marked pigmentation, and histology

Pemphigus vulgaris – Distinguished by the clinical picture, bullae on unchanged skin, localization, cytodiagnostics, and histologic features

Lupus erythematosusacutusetsubacutusdisseminatus – Distinguished by the general state, variable skin manifestation, infiltrates, red wine–colored transient erythemas on the palms and digits, lupus erythematosus phenomenon, proteinuria, and cylindruria

Chronic polymorphic light dermatoses – Distinguished by erythema on light-exposed sites, recurring papules, pruriginous nodules, lichenification, lack of marked pigmentation, and scaling

Hartnup syndrome – Recessive hereditary disorder distinguished by the malabsorption of tryptophan, pellagrous skin lesions, hypersensitivity to sun exposure, poikiloderma, onset in childhood, absence of mucous membrane disorder and diarrhea, various nervous and psychiatric aberrations, intermittent cerebellar ataxia, aminoaciduria, and marked indicanuria

Kwashiorkor – Distinguished by occurrence in children, dietary history, protein deficiency, generalized eruption, dermatitis with systemic signs of apathy and edema, thin and light hair, and high mortality rate

Porphyria cutaneatarda – Distinguished by bullae on exposed sites, bullae development after mechanical injury, porphyrins in the urine, and characteristic liver function test findings and medical findings in the liver

Porphyria variegata – Distinguished by erythema and bullae, skin and abdominal symptoms in attacks, and porphyrins in the urine and stool

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The recommend daily allowance (RDA) for niacin is 16 milligrams per day for men and 14 milligrams per day for women. Good sources of niacin include red meat, fish, poultry, fortified breads and cereals, and enriched pasta and peanuts.

If you don’t eat a lot of niacin-rich foods or if you have a medical condition that affects the absorption of niacin or tryptophan, speak to your doctor. Niacin supplements or multivitamin/mineral supplements, which usually contain at least 20 milligrams of niacin, can help prevent niacin deficiency.

Supplements of niacin such as nicotinic acid or nicotinamide are approved by the FDA for treating niacin deficiency. Under the supervision of a doctor, high doses of over-the-counter or prescription niacin or nicotinic acid can be used to treat high cholesterol, including high triglycerides. However, too much nicotinic acid or niacin can be harmful. Avoid taking more than your doctor prescribes or recommends. If you are taking doses of more than 100 milligrams per day, doctors recommend periodic liver function tests.

By Medifit Biologicals