Effect of niacin supplementation on nausea-like behaviour in an isoniazid-induced mouse model of pellagra.

Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.

Pathophysiology and clinical management of pellagra - a review.

Pellagra is a rare disease caused by niacin deficiency or a disruption of its metabolism. Its manifestations are dermatitis with pronounced photosensitivity, gastrointestinal symptoms, and neuropsychiatric ailments. Currently pellagra is developed in people who chronically abuse alcohol or are treated with medications from specific pharmacological groups (immunosuppressive and anti-tuberculosis drugs). Although the root cause of the disease was established in the mid-twentieth century, a detailed explanation of the processes leading to the development of symptoms has not yet been proposed. They include complex abnormalities at the molecular, metabolic, and immunological levels. Diagnostics is based primarily on the clinical presentation of the disease, while auxiliary tests play secondary role. The low prevalence of the disease, meaning that physicians are unfamiliar with its recognition, often leads to delays in diagnosis and appropriate treatment. The therapy is causal and based on administering niacinamide. Failure to implement treatment in the early stages of the disease leads to the patient's death. The aim of this literature review is to summarize the current state of knowledge on the pathomechanisms of pellagra, highlighting the clinical implications, and key elements of diagnostic and therapeutic management that are important in the treatment of pellagra patients.

Pellagra secondary to selective eating in a child with autism.

Once a significant cause of morbidity and mortality, health care providers rarely see primary pellagra in developed countries where fortification of foods with niacin is commonplace and niacin-rich foods are generally widely available. We report a ten-year-old boy with autism spectrum disorder who presented with photosensitive dermatitis which resolved after vitamin supplementation and dietary changes. In this child, the pellagra developed as the result of a long-term pattern of selective eating. Restricted diets, even to the point of nutrient deficiencies, are well-documented among children with autism spectrum disorders (ASD).

Pellagra and anorexia nervosa: a case report.

BACKGROUND: While pellagra appears to be a rare entity currently, it may still develop. It is important to recognize how the disease manifests to ensure adequate and timely treatment. CASE PRESENTATION: We present a case of pellagra secondary to anorexia nervosa in a 28-year-old woman. We observed the classical signs: erythema in the neck region, diarrhea, and neurologic symptoms. Diagnosis was made on a clinical basis, and the patient had a rapid recovery after undergoing therapy with nicotinamide and tryptophan. CONCLUSIONS: In our case, the patient did not exhibit any sign of being severely underweight with marked malnutrition such as the typical manifestation expected in pellagra. This case demonstrated that clinicians should have a high level of suspicion in making a diagnosis of pellagra, especially in patients with a history of eating disorders. LEVEL OF EVIDENCE: IV (case study).

Pellagra and Alcohol Dependence Syndrome: Findings From a Tertiary Care Addiction Treatment Centre in India.

AIM: To define the prevalence and clinical presentation of pellagra, a multi-systemic disease caused by the deficiency of niacin, in patients admitted to a tertiary addiction treatment centre in southern India, with alcohol dependence syndrome (ADS)-(ICD10). METHODS: Review of the health records of 2947 patients who received inpatient care for ADS between 2015 and 2017. RESULTS: Out of 2947, 31 (1%) were diagnosed with pellagra. Nearly two-thirds (64.5%) of those with pellagra were from a low-income group. Of the clinical-triad of pellagra, all patients had dermatitis, more than half (58%) had delirium, a minority (19%) had diarrhoea. Nearly two-thirds (61%) had presented in a complicated-withdrawal state. Associated conditions included peripheral neuropathy (32%); Wernicke's encephalopathy (26%); seizures (16%).Seventeen (54%) had BMI <18.5 kg/m2. Treatment was a high dose of parenteral vitamins including niacin (mean dose: 1500 mg/day) for an average of 7.5 days followed by oral multivitamin supplements. All had complete resolution of pellagrous symptoms by the end of the three weeks of inpatient care. CONCLUSIONS: Pellagra is an acute medical condition, frequently encountered in the context of alcohol dependence and poverty. It often presents with other disabling and life-threatening comorbidities like delirium tremens and Wernicke's encephalopathy. The classical triad of pellagra is only seen in a minority of cases. Thus a high index of suspicion is required lest pellagra may remain undiagnosed. Prompt identification and treatment with a high dose of niacin in combination with other vitamins result in complete recovery.

The Pellagra Portraits.

This Arts and Medicine feature reviews the history of pellagra and recounts the role of artist and illustrator John Carroll who, in 1919, painted portraits of people with the vitamin deficiency to document in color the appearance of pellagra skin plaques.

Severe pellagra masked by concurrent plaque psoriasis: a case report of a hidden diagnosis.

Despite characteristic features, psoriasis can mimic other dermatologic conditions, such as seborrheic dermatitis, lichen simplex chronicus, and certain nutritional deficiencies such as pellagra. We present a patient with a longstanding history of severe plaque psoriasis who presented with disfiguring scaly plaques involving greater than 80% body surface area. The patient's disease was minimally responsive to multiple therapies. Repeat punch biopsies demonstrated parakeratosis, psoriasiform hyperplasia, and dilated blood vessels consistent with psoriasis. Given atypical clinical features and overall poor treatment response additional work up was obtained. A serum nutritional panel was consistent with niacin deficiency and the patient later revealed extensive alcohol intake. A diagnosis of concurrent pellagra was made and the patient was started on niacin supplementation and instructed to reduce alcohol intake, while continuing adalimumab and high potency topical steroids. Within two weeks, his disease had markedly improved. Pellagra presents characteristically with a photosensitivity dermatitis that may appear clinically and histologically similar to psoriasis. It is important to maintain an index of suspicion for a secondary pathology in treatment-resistant psoriasis.

'Shrouded in a dark fog': comparison of the diagnosis of pellagra in Venice and general paralysis of the insane in the United Kingdom, 1840-1900.

The debate on the causes and the nature of pellagra in Italy during the nineteenth century resembles and evokes the similar debate on General Paralysis of the Insane (GPI) that was growing at the same time in the United Kingdom. Pellagra and GPI had a massive and virulent impact on the populations of Italy and the UK, respectively, and contributed to a great extent to the increase and overcrowding of the asylum populations in these countries. This article compares the two illnesses by examining the features of their nosographic positioning, aetiology and pathogenesis. It also documents how doctors arrived at the diagnoses of the two diseases and how this affected their treatment.

Pellagra Pre-Goldberger: Rupert Blue, Fleming Sandwith, and The "Vitamine Hypothesis".

The conquest of pellagra is commonly associated with one name: Joseph Goldberger of the US Public Health Service, who in 1914 went south, concluded within 4 months that the cause was inadequate diet, spent the rest of his life researching the disease, and--before his death from cancer in 1929--found that brewer's yeast could prevent and treat it at nominal cost. It does Goldberger no discredit to emphasize that between 1907 and 1914 a patchwork coalition of asylum superintendents, practicing physicians, local health officials, and others established for the first time an English-language competence in pellagra, sifted through competing hypotheses, and narrowed the choices down to two: an insect-borne infection hypothesis, championed by the flamboyant European Louis Westerna Sambon, and the new "vitamine hypothesis," proffered by Casimir Funk in early 1912 and articulated later that year by two members of the American Clinical and Climatological Association, Fleming Mant Sandwith and Rupert Blue. Those who resisted Goldberger's inconvenient truth that the root cause was southern poverty drew their arguments largely from the Thompson-McFadden Pellagra Commission, which traces back to Sambon's unfortunate influence on American researchers. Thousands died as a result.

Ethionamide-induced Pellagra.

Pellagra is a disorder characterized by dermatitis, diarrhea, dementia and eventually death, resulting from a deficiency of niacin or its precursor tryptophan. Ethionamide (a second-line antituberculosis agent)-induced pellagra is rarely encountered in clinical practice. Prompt diagnosis and treatment with nicotinamide can prevent life-threatening complications. To date, only three cases have been reported. We report a 13-year-old girl presenting with ethionamide-induced pellagra that resolved after the administration of niacin.