Pellagra in the USA: unusual manifestations of a rare entity.

The case involves a 62-year-old female native of the USA with a history of bipolar disorder and chronic obstructive pulmonary disease who presented with intractable diarrhoea. Prior to the index admission, she was admitted to the intensive care unit and required pericardiocentesis for an idiopathic pericardial effusion with tamponade physiology. Following discharge, she suffered intractable diarrhoea and represented for medical evaluation. She had a painful, swollen tongue as well as persistent hypoglycaemia and required glucose infusions. She had adrenal function testing which revealed adrenal insufficiency. Vitamin testing revealed normal B12 and folate levels but undetectable levels of thiamine, riboflavin and niacin. Her symptoms and signs resolved entirely with appropriate vitamin supplementation. Niacin (vitamin B3) is essential for multiple metabolic pathways, and severe deficiency may cause clinical syndrome of pellagra which is most commonly associated with diarrhoea, delirium and dermatitis. Additional physiological derangements may include adrenal insufficiency, insulin hypersensitivity and pericarditis.

Evidence and conjecture about mechanisms of cutaneous disease in photodermatology.

Photosensitivity disorders are caused by a variety of mechanisms. Three common themes are as follows: excess chromophore allowing visible light energy to cause photodynamic damage, reduced DNA repair capacity to UV-induced DNA damage, and enhanced sensitivity to light-induced allergens mediated immunologically. Although the cause of each condition may be known, the precise pathogenesis underlying the photosensitivity has taken longer to understand. By focussing on three clinical disorders under each of these themes, we have explored the following: why erythropoietic protoporphyria differs so markedly from the other cutaneous porphyrias; how a DNA repair defect was eventually revealed to be the underlying cause of the vitamin B3 deficiency disorder of pellagra; an immunological explanation for the over reactivity to photoallergens in chronic actinic dermatitis.

The discovery of niacin, biotin, and pantothenic acid.

The aim was to describe the discovery of niacin, biotin, and pantothenic acid. By the 1920s, it became apparent that 'water-soluble B' (vitamin B) is not a single substance. In particular, fresh yeast could prevent both beriberi and pellagra, but the 'antipolyneuritis factor' in yeast is thermolabile, while the antipellagra factor is heat stable, suggesting that there are at least two water-soluble vitamins. Various terms were proposed for these water-soluble factors, but vitamins B(1) and B(2) were most widely used to refer to the thermolabile and heat-stable factors, respectively. Although vitamin B(1) proved to be a single chemical substance (thiamin), vitamin B(2) was ultimately found to be a complex of several chemically unrelated heat-stable factors, including niacin, biotin, and pantothenic acid. Recognition that niacin is a vitamin in the early 20th century resulted from efforts to understand and treat a widespread human disease - pellagra. American epidemiologist and US Public Health Service officer Joseph Goldberger (1874-1929) had been instrumental to elucidating the nutritional basis for pellagra. Goldberger conducted a classic series of observational and experimental studies in humans, combined with an extensive series of experiments with an animal model of the condition (black tongue in dogs). In contrast, recognition that biotin and pantothenic acid are vitamins occurred somewhat later as a result of efforts to understand microbial growth factors. The metabolic roles in humans of these latter substances were ultimately elucidated by human experiments using particular toxins and by studies of rare inborn errors of metabolism. Symptomatic nutritional deficiencies of biotin and pantothenic acid were, and continue to be, rare.

Electrocardiographic enigma of a classical disease: pellagra.

Pellagra is caused by a deficiency of niacin. It is endemic in Africa and Asia where the staple diet of the many refugees or displaced people is corn-based and, therefore, nicotinic acid-deficient. It is also frequently seen in developed countries among chronic alcoholics or, occasionally, those suffering from anorexia nervosa. The usual manifestations are diarrhoea, dementia and dermatitis (the 3Ds), which if left untreated may lead to death. Cardiac manifestations and electrocardiographic changes are rarely seen in those suffering from pellagra. We present a case of pellagra in an alcoholic who presented with the classical rash over the upper limbs along with electrocardiographic changes but without any cardiac symptoms, both of which resolved dramatically after he had been given niacin supplements.

Intestinal permeability and oxidative stress in patients with alcoholic pellagra.

BACKGROUND & AIMS: Increased intestinal permeability is one of the grastointestinal changes observed in alcoholic patients. However, there are no objective definitions as yet of how alcohol induces pathological changes in the various organs. The action of oxygen-free radicals during ethanol metabolism has been considered a determinant factor of these alterations. The present study was undertaken to determine the effect of niacin supplementation on intestinal permeability and oxidative stress in patients with alcoholic pellagra. METHODS: The study was divided into two phases: in Phase 1 we studied ten patients with pellagra before treatment with niacin, and in Phase 2 we studied the same patients after 27 days of treatment with niacin. Intestinal permeability was assessed by the (51)CrEDTA test and the antioxidant action of niacin supplementation was assessed by the determination of lipid peroxidation (plasma malondialdehyde, MDA), protein oxidation (plasma carbonyl group) and of the antioxidants plasma vitamin E and erythrocyte glutathione peroxidase. RESULTS: Comparison of intestinal permeability by the (51)CrEDTA test before and after niacin treatment showed a significant decrease in permeability from 4.29+/-1.92% to 1.90+/-1.19% (P<0.05). Assessment of oxidative stress showed a significant decrease (P<0.05) in lipid and protein peroxidation (MDA: 1.19+/-0.40-0.89+/-0.27 micromol/l; carbonyl groups: 2.22+/-0.36-1.84+/-0.40 nmol/mg protein). CONCLUSIONS: The results suggest that niacin and vitamin E deficiency in patients with pellagra could be important factors in increased intestinal permeability and decreased antioxidant conditions, recovering to normal values after treatment with niacin, associated to alcohol abstinence and a balanced diet.

Pellagra y piel / Pellagra and skin

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Efectos del alcohol etílico sobre el sistema nervioso / No disponible

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Niacin as a potential AIDS preventive factor.

A pentad of findings consistent with niacin depletion have been described in patients with AIDS. There are also clinical and laboratory data to support the potential benefit of niacin in HIV infection. In this paper, it is hypothesized that HIV infection induces niacin depletion, and that therapeutic niacin will act as an AIDS preventive factor. While viral inhibition is incontrovertibly the primary 'AIDS preventive factor', costly antiretroviral medications are simply out of reach for the majority of the world's HIV-infected people. Along with antiviral research, investigation must go forward to look at strategies to overcome the massive metabolic disruption caused by the production of approximately one billion virus particles per day. Niacin, the same B complex vitamin found in the early part of this century to be the 'pellagra preventive factor', is proposed here as a secondary 'AIDS preventive factor' in HIV-infected persons.

[Pellagra: diagnosis still valid]. / Pelagra: diagnóstico aún vigente.

Pellagra, caused by niacin deficiency, was described in 1730 by Casal in Spain and is specially frequent in alcoholics, subjects with malabsorption and mentally ill patients. We report three alcoholic patients (one female) aged 32, 57 and 26 years old, presenting with the typical desquamative and hyperpigmented lesions in exposed areas. One patient also had mental changes characterised by aggressiveness and clouding of consciousness. A diagnosis of pellagra was reached and treatment with nicotinic acid was started with good clinical response in all cases.

Estudios sobre el niño desnutrido. IV pruebas del fucionamiento hepático en el preescolar sano y en el desnutrido, en el niño pelagroso y en el infectado / Studies in malnourished children. IV. Hepatic tests in the healthy, and in the malnourished preschool child; in the pellagrose, and in the infected

Se practicaron las pruebas de retención de la bromosulfaleína y la dosificación de bilirrubina directa e indirecta en un grupo de niños desnutridos, sin encontrar anormalidad en los resultados. En un grupo de 50 niños considerados sanos, se realizaron las pruebas de cefalín-colesterol y de timol. Otro tanto se hizo con 58 desnutridos simples y 48 pelagrosos estudiados separadamente, según existiese o no en ellos, la infección. Por lo que respecta a las pruebas de tinol y de cefalín-colesterol en los preescolares estudiados, se encontró lo siguiente: a) En la desnutrición simple, ligera o avanzada, no se modificaron las pruebas funcionales hepáticas empleadas por nosotros. b) En los niños con pelagra sin complicación infecciosa tampoco se encontraron alteradas las pruebas de funcionamiento hepático. c) Las pruebas anormales de timol que se encontraron en los niños desnutridos o pelagrosos, deben ser atribuidas a la infección o a procesos de regeneración hepática. d) Los resultados anormales de la prueba de cefalín-colesterol que se encontraron en los niños desnutridos y pelagrosos deben ser atribuidos exclusivamente a la infección

Alcoholic dementia.

At least four distinct cerebral diseases--Wernicke-Korsakoff, Marchiafava-Bignami, pellagrous encephalopathy, and acquired hepatocerebral degeneration--have a close association with chronic alcoholism. Each is characterized by a distinctive pathologic change and a reasonably well-established pathogenesis; in each the role of alcohol in the causation is secondary. The question posed in this review is whether there is, in addition to the established types of dementia associated with alcoholism, a persistent dementia attributable to the direct toxic effects of alcohol on the brain--i.e., a primary alcoholic dementia. The clinical, psychologic, radiologic, and pathologic evidence bearing on this question is critically reviewed. None of the evidence permits the clear delineation of such an entity. The most serious flaw in the argument for a primary alcoholic dementia is that it lacks a distinctive, well-defined pathology, and it must remain ambiguous until such time as its morphologic basis is established.

Pellagra--increased viscosity of extracellular matrix.

Pellagra is the result of increased viscosity of extracellular matrix (ECM). The skin changes in pellagra localize at sites of sun exposure or trauma because the mediators which are released cannot diffuse from the area. Edema is reported as the first clinical and microscopic change. Changes in the ECM are not directly visible. Increased viscosity of ECM in the gastrointestinal tract would decrease absorption of fluid and nutrients from the bowel resulting in diarrhea. In the tongue the excess ECM viscosity holds water producing swelling. The effect of climate and seasons relates to the increased demand for ECM repair on sunlight exposed areas. Infections increase the severity of pellagra by requiring increased tissue repair. Local infections are often unusually severe. Infections have a greater inflammatory component at sites of high ECM viscosity. Nicotinic acid reverses the neurologic and gastrointestinal changes of pellagra in 24 h. This suggests a simple rapid mode of action. Nicotinic acid plays a major role in tissue respiration which is essential for tissue repair and degradation of glycosaminoglycans. Altering ECM viscosity is a method of modulating inflammation, immunity, and normal tissue physiology.

[The urinary metabolites of niacin during the course of pellagra]. / Les métabolites urinaires de la niacine au cours de la pellagre.

The three main metabolites of niacin have been measured in urine of 10 Mozambican women living in refugee camps in Malawi and displaying clinical symptoms of pellagra. This study, in which a control group was included, showed that the ratio 6PYR/N1MN is well correlated to the occurrence of clinical symptoms of niacin deficiency and constitutes a reliable indicator of vitamin PP status in subjects at risk of this deficiency.

The clinical spectrum of alcoholic pellagra encephalopathy. A retrospective analysis of 22 cases studied pathologically.

A retrospective clinical study of 22 heavy alcohol drinkers is reported in which postmortem study showed diffuse chromatolysis of neurons identical to that found in neurological pellagra, associated in 13 cases with Marchiafava-Bignami disease and/or Wernicke-Korsakoff disease. The clinical features included confusion and/or clouding of consciousness, marked oppositional hypertonus ('gegenhalten') and myoclonus. Because of the frequent coexistence of other alcoholic encephalopathies in the same patient, alcoholic pellagra was often unrecognized. Fifteen patients received thiamine and pyridoxine therapy without niacin. It appeared to aggravate the neurological state or to trigger the development of alcoholic pellagra encephalopathy in 9 cases. The relationship between pellagra occurring during thiamine and pyridoxine therapy and 'nicotinic acid deficiency' is discussed. Multiple vitamin therapy should be given in the treatment of undiagnosed encephalopathies in alcoholic patients.