Phenobarbital-induced pellagra resulted in death.

Pellagra is caused by deficiency of niacin or its precursor tryptophan. While cutaneous lesions are the most prominent feature of the disease, gastrointestinal, neurological and psychiatric signs and symptoms are the other characteristics of the disease. In this case report, we present a 29-year-old female patient with discoloration of hands and feet diagnosed with pellagra.

Niacin: vitamin and antidyslipidemic drug.

Niacin is defined collectively as nicotinamide and nicotinic acid, both of which fulfill the vitamin functions of niacin carried out by the bioactive forms NAD(P). In the last few decades numerous new enzymes that consume NAD(P) as substrates have been identified. The functions of these enzymes are emerging as exciting paradigm shifts, even though they are in early stages of discovery. The recent identification of the nicotinic acid receptor has allowed distinction of the drug-like roles of nicotinic acid from its vitamin functions, specifically in modulating blood lipid levels and undesirable side effects such as skin vasodilation and the more rare hepatic toxicities. This information has led to a new strategy for drug delivery for niacin, which, if successful, could have a major impact on human health through decreasing risk for cardiovascular disease. Understanding the many other effects of niacin has much broader potential for disease intervention and treatment in numerous diseases including cancer.

Whole blood NAD and NADP concentrations are not depressed in subjects with clinical pellagra.

Population surveys for niacin deficiency are normally based on clinical signs or on biochemical measurements of urinary niacin metabolites. Status may also be determined by measurement of whole blood NAD and NADP concentrations. To compare these methods, whole blood samples and spot urine samples were collected from healthy subjects (n = 2) consuming a western diet, from patients (n = 34) diagnosed with pellagra and attending a pellagra clinic in Kuito (central Angola, where niacin deficiency is endemic), and from female community control subjects (n = 107) who had no clinical signs of pellagra. Whole blood NAD and NADP concentrations were measured by microtiter plate-based enzymatic assays and the niacin urinary metabolites 1-methyl-2-pyridone-5-carboxamide (2-PYR) and 1-methylnicotinamide (1-MN) by HPLC. In healthy volunteers, inter- and intra-day variations for NAD and NADP concentrations were much lower than for the urinary metabolites, suggesting a more stable measure of status. However, whole blood concentrations of NAD and NADP or the NAD:NADP ratio were not significantly depressed in clinical pellagra. In contrast, the concentrations of 2-PYR and 1-MN, expressed relative to either creatinine or osmolality, were lower in pellagra patients and markedly higher following treatment. The use of the combined cut-offs (2-PYR <3.0 micromol/mmol creatinine and 1-MN <1.3 micromol/mmol creatinine) gave a sensitivity of 91% and specificity of 72%. In conclusion, whole blood NAD and NADP concentrations gave an erroneously low estimate of niacin deficiency. In contrast, spot urine sample 2-PYR and 1-MN concentrations, relative to creatinine, were a sensitive and specific measure of deficiency.

Low and deficient niacin status and pellagra are endemic in postwar Angola.

BACKGROUND: Outbreaks of pellagra were documented during the civil war in Angola, but no contemporary data on the incidence of pellagra or the prevalence of niacin deficiency were available. OBJECTIVE: The objective was to investigate the incidence of pellagra and the prevalence of niacin deficiency in postwar Angola and their relation with dietary intake, poverty, and anthropometric status. DESIGN: Admissions data from 1999 to 2004 from the pellagra treatment clinic in Kuito, Angola, were analyzed. New patients admitted over 1 wk were examined, and urine and blood samples were collected. A multistage cluster population survey collected data on anthropometric measures, household dietary intakes, socioeconomic status, and clinical signs of pellagra for women and children. Urinary excretion of 1-methylnicotinamide, 1-methyl-2-pyridone-5-carboxymide, and creatinine was measured and hemoglobin concentrations were measured with a portable photometer. RESULTS: The incidence of clinical pellagra has not decreased since the end of the civil war in 2002. Low excretion of niacin metabolites was confirmed in 10 of 11 new clinic patients. Survey data were collected for 723 women aged 15-49 y and for 690 children aged 6-59 mo. Excretion of niacin metabolites was low in 29.4% of the women and 6.0% of the children, and the creatinine-adjusted concentrations were significantly lower in the women than in the children (P < 0.001, t test). In children, niacin status was positively correlated with the household consumption of peanuts (r = 0.374, P = 0.001) and eggs (r = 0.290, P = 0.012) but negatively correlated with socioeconomic status (r = -0.228, P = 0.037). CONCLUSIONS: The expected decrease in pellagra incidence after the end of the civil war has not occurred. The identification of niacin deficiency as a public health problem should refocus attention on this nutritional deficiency in Angola and other areas of Africa where maize is the staple.

Serum electrolytes in hospitalized pellagra alcoholics.

BACKGROUND: Owing to high diarrhoea and protein malnutrition frequencies in pellagra, we hypothesised that pellagra patients would have higher electrolyte disturbances than non-pellagra alcoholics. OBJECTIVE: To compare serum electrolytes of hospitalised alcoholics with or without pellagra. DESIGN: Retrospective and descriptive case-control study. SETTING: Internal Medicine wards at a University Hospital, Medical School of Uberaba, Brazil. SUBJECTS: Medical records were reviewed to obtain relevant clinical details, main diagnosis and laboratory data, including serum electrolytes on hospital admission of pellagra patients (n=33) and a randomly chosen control group of alcoholics (n=37), matched in age, gender and socio-economic status. Anaemia was ascertained by haemoglobin <12.5 g/dl (men) and 1.5 g/dl (women), and hypoalbuminemia by serum albumin <3.3 g/dl. RESULTS: Pellagra and controls showed similar age (39.4+/-13.1 vs 45.0+/-11.4 years) and a male predominance of gender (69.7 vs 78.4%), and similar associated diagnoses, including high blood pressure (21.2 vs 16.2%), peripheral neuropathy (12.1 vs 13. 5%), and pneumonia (9.1 vs 13.5%). Despite displaying similar serum sodium (136.6+/-6.1 vs 137.8+/-5.7 mEq/I), magnesium (1.72+/-0.74 vs 1.62+/-0.34 mg/dl), phosphorus (3.79+/-0.87 vs 3.87+/-0.78 mEq/1) than controls,in addition to higher hypoalbuminemia (76.2 vs 33%) and anaemia (60.6 vs 35.1%) frequencies. CONCLUSIONS: Higher anaemia and hypoalbuminemia frequencies associated with lower serum potassium levels suggest increased protein malnutrition prevalence among pellagrins.

[Prevalence of HIV infection in patients with pellagra and pellagra-like erythemas]. / Prévalence de l'infection par le VIH au cours de la pellagre et des érythèmes pellagroïdes.

Pellagra is a systemic disorder caused by severe niacin deficiency. While uncommon in Europe and North America, pellagra and pellagra-like erythema are frequently encountered in undernourished adults in poor African countries. The purpose of this three-year prospective study was to determine the prevalence of HIV infection in patients with pellagra. Between 1996 and 1998, all documented cases of pellagra and pellagra-like erythema diagnosed in the Dermatology Department and Internal Medicine Department of the Teaching Hospital in Lome, Togo were included. Patients underwent screening tests for HIV infection. During the study period, pellagra or pellagra-like erythema was diagnosed in a total of 108 patients (59 women and 49 men) with a mean age of 41 +/- 3.5 years (range, 18 to 68 years). Serology tests for HIV were positive in 6 of these patients (5.5 p. 100; mean age 35 years). In four asymptomatic patients with no opportunistic infection, detection of HIV was an incidental discovery. The other two patients had AIDS symptoms. The principal causes of pellagra were malnutrition (n = 30), alcoholism (n = 15), and combined malnutrition and alcoholism (n = 60). The findings of this study suggest that the incidence of HIV infection in patients with pellagra and pellagra-like erythema is low, i.e., not higher than in the general population. This study also confirms previous etiologic and epidemiological data concerning pellagra in poor countries, i.e., the preponderant role of nutritional deficiency.

[Dose-dependent pellagroid skin reaction caused by carbamazepine]. / Dosisabhängige pellagroide Hautreaktion durch Carbamazepin.

A 11-year-old girl suffering from grand mal epilepsy underwent antiepileptic therapy with carbamazepine (600 mg/daily). Two weeks after increasing the dose (900 mg/day) she suddenly developed relatively sharply limited, sunburn-like brown reddish macular lesions with central scaling and partly hyperkeratotic areas on the hands, feet, face, knees, gluteal and axillar regions. Otherwise no health disorders were found; in particular no neurological or gastrointestinal symptoms occurred. After reduction of the doses (450 mg/day) these skin lesions faded away. With exception of elevated serum levels of carbamazepine, nicotinamide and vitamin B6, all blood tests were in normal range. Interactions of carbamazepine with the vitamin B6- nicotinamide metabolism are the reason for these previously undescribed cutaneous side effects in connection with carbamazepine therapy. The present case demonstrates a toxic, non-allergic reaction during carbamazepine treatment with pellagroid skin symptoms.

Plasma amino acid patterns in alcoholic pellagra patients.

Plasma amino acid concentrations in 33 male alcoholic patients with pellagra (age 20-68 years) were compared with those in 17 healthy male subjects (age 20-45 years). Pellagra diagnosis was made on the basis of the typical clinical skin picture, and low urinary excretion of N'methylnicotinamide and N'methyl-2-pyridone-5-carboxamide (reduced by 70 and 80%, respectively, compared with controls). There were significant differences in body mass index, creatinine/high index and serum albumin between the two groups, indicating that besides pellagra the alcoholic patients had some degree of malnutrition. Of 17 plasma amino acids measured, the following had significantly lower concentrations in the pellagrins: tryptophan (3.65 vs 5.93 mumol/dl, pellagrin vs control), isoleucine (6.31 vs 11.13), leucine (11.54 vs 24.19), lysine (16.25 vs 34.47), methionine (2.61 vs 4.22), phenylalanine (5.71 vs 9.23), threonine (13.29 vs 26.81), valine (17.60 vs 41.06), alanine (42.54 vs 70.87), arginine (5.87 vs 10.09), tyrosine (5.57 vs 9.30). Glutamic acid was significantly higher in the pellagrins (18.45 vs 9.49). There was no difference between the groups of aspartic acid, glycine, histidine, proline and serine concentrations. It is concluded that pellagra is an important factor influencing the amino acid profiles in these patients. This finding should be taken into account when using plasma amino acid levels to assess the clinical status of the pellagrin.

Nutritional deficiencies in patients receiving cancer chemotherapy.

Cancer often causes malnutrition and specific vitamin and protein deficiencies. Chemotherapy also causes deficiencies by promoting anorexia, stomatitis, and alimentary tract disturbances. Antimetabolite drugs in particular inhibit synthesis of essential vitamins, purines, and pyrimidines. Because vitamin levels in the blood are often nondiagnostic, nutritional deficiency is identified almost exclusively on the basis of clinical signs and symptoms and the patient's response to therapy. Signs and symptoms of cachexia and hypoalbuminemia are common in patients with advanced cancer. Deficiencies of vitamins B1, B2, and K and of niacin, folic acid, and thymine also may result from chemotherapy. Nutritional deficiencies are chemically correctable; however, the tumor must be eradicated to relieve cachexia.

Elevated glutamic acid values in a malnourished patient. A case report.

Routine serum and cerebrospinal (CSF) amino acid estimations were carried out on a patient with pellagra and malnutrition. Urea levels were low and serum and CSF ammonia levels elevated. A remarkable observation was that the serum glutamic acid level rose to 44.9 times normal, which is far higher than any value reported in the medical literature. At this stage no explanation for this rise is known. Similarly no explanation can be given for the posttreatment elevation of the CSF proline levels to 13.8 times above normal.

Study of blood pyruvic acid levels in pellagrins with and without neurological manifestations and response to nicotinic acid therapy.

In 25 cases of pellagra and 10 healthy controls, the blood pyruvic acid levels in the fasting stage and after 60 and 90 minutes of glucose load were estimated by the technique of Friedmann & Haugen (1943). The blood pyruvic acid levels after 60 and 90 minutes of glucose load were significantly higher in pellagrins as compared to controls. The following conclusions were drawn from this study: (i) that there is impairment of pyruvic acid metabolism in cases of pellagra, which is more marked in pellagrins with neurological manifestations than in those without; (ii) that after administration of nicotinic acid alone for 15 days the pyruvic acid levels returned to normal, thereby indicating that nicotinic acid deficiency is the cause of deranged pyruvate metabolism; (iii) that there is significant improvement in neurological status after nicotinic acid therapy.

Plasma amino acid pattern in pellagra.

Plasma free amino acid levels were determined in subjects suffering from pellagra and compared with levels observed in normal subjects of both low and high socioeconomic groups. In pellagrins, a wide variation was seen in the plasma levels of tryptophan and these levels overlapped considerably with those in the low socioeconomic group controls. Administration of 5 g L-leucine daily for 5 days to normal subjects belonging to the low socioeconomic group did not affect the plasma tryptophan levels. These data suggest that the pellagragenic action of leucine is not mediated through changes in circulating levels of tryptophan. They also indicate that a low level of plasma tryptophan per se may not be a reliable biochemical indicator in the diagnosis of pellagra.