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Advances in Clinical Neuroscience &... 2020Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt for the diseases and social consequences of poverty (and of affluence)...
Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt for the diseases and social consequences of poverty (and of affluence) that often involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption of NAD from genotoxic and other stresses. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome giving a mechanism for a new hypervitaminosis-B3.
PubMed: 38125674
DOI: 10.47795/FBFD9966 -
The Lancet. Global Health May 2022Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and...
BACKGROUND
Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population.
METHODS
We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily.
FINDINGS
Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement.
INTERPRETATION
Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further.
FUNDING
This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.
Topics: Antitubercular Agents; Case-Control Studies; Exanthema; Female; HIV Infections; Humans; Isoniazid; Male; Niacin; Pellagra; Tuberculosis; Vitamin B Complex
PubMed: 35427527
DOI: 10.1016/S2214-109X(22)00096-1 -
Journal Der Deutschen Dermatologischen... Sep 2022
Topics: Humans; Niacin; Pellagra
PubMed: 35979943
DOI: 10.1111/ddg.14843 -
AACE Clinical Case Reports 2023Micronutrient deficiencies such as pellagra are rarely seen after bariatric surgery and can be challenging to diagnose and manage. Alcohol use can precipitate...
BACKGROUND/OBJECTIVE
Micronutrient deficiencies such as pellagra are rarely seen after bariatric surgery and can be challenging to diagnose and manage. Alcohol use can precipitate nutritional deficiencies.
CASE REPORT
A 51-year-old woman with a history of Roux-en-Y gastric bypass surgery who later developed an alcohol-use disorder after her diagnosis of breast cancer. She experienced a subacute decline in her physical and cognitive function along with a rash after radiation treatment for breast cancer, lower extremity pain and weakness, anemia, and diarrhea with severe hypokalemia. Workup showed undetectable niacin levels. She initially did not respond to an oral niacin replacement, necessitating intramuscular injections. Alcohol cessation and parenteral B complex replacement led to the resolution of her symptoms and biochemical derangements.
DISCUSSION
Bariatric surgery with concomitant alcohol use can precipitate niacin deficiency-induced liver dysfunction. In the correct clinical setting, screening for alcohol use and checking niacin levels may help avoid extensive testing and can help make the correct diagnosis. Parenteral replacement may be necessary in this setting.
CONCLUSION
Niacin deficiency needs to be considered in patients with bariatric surgery with a history of alcoholism in the correct clinical setting.
PubMed: 37251973
DOI: 10.1016/j.aace.2023.04.002 -
Metabolites Sep 2019Nicotinamide adenine dinucleotide (NAD) has a critical role in cellular metabolism and energy homeostasis. Its importance has been established early with the discovery... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) has a critical role in cellular metabolism and energy homeostasis. Its importance has been established early with the discovery of NAD's therapeutic role for pellagra. This review addresses some of the recent findings on NAD physiopathology and their effects on nonalcoholic fatty liver disease (NAFLD) pathogenesis, which need to be considered in the search for a better therapeutic approach. Reduced NAD concentrations contribute to the dysmetabolic imbalance and consequently to the pathogenesis of NAFLD. In this perspective, the dietary supplementation or the pharmacological modulation of NAD levels appear to be an attractive strategy. These reviewed studies open the doors to growing interest in NAD metabolism for NAFLD diagnosis, prevention, and treatment. Future rigorous clinical studies in humans will be necessary to validate these preliminary but promising results.
PubMed: 31510030
DOI: 10.3390/metabo9090180 -
International Journal of Molecular... Nov 2019Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine... (Review)
Review
Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.
Topics: Animals; Energy Metabolism; Genomic Instability; Humans; Immunosuppression Therapy; NAD; Niacinamide; Skin Aging; Skin Neoplasms; Ultraviolet Rays
PubMed: 31779194
DOI: 10.3390/ijms20235946 -
Saudi Journal of Kidney Diseases and... 2020Pellagra usually results from niacin deficiency and presents with the classic triad of dermatitis, diarrhea, and dementia. It is most commonly associated with...
Pellagra usually results from niacin deficiency and presents with the classic triad of dermatitis, diarrhea, and dementia. It is most commonly associated with malnutrition and poverty. We report a case of pellagra in a hemodialysis (HD) patient with breast neoplasia, aged 68-years, female, on HD unit for seven years. Her original nephropathy was indeterminate. The patient was followed up for homozygous beta-thalassemia and breast neoplasia with hepatic metastases on chemotherapy. The body mass index of the patient was 18.5 kg/m. Physical examination showed a thickening of the epidermis with a scaly surface, pigmented, and atrophied areas. We noted neuropsychiatric signs (apathy, irritability, anorexia, and depression) and digestive symptomatology (diarrhea). The laboratory tests revealed hypoproteinemia at 55 g/L, hypoalbuminemia at 21 g/L, and hypocholesterolemia at 0.8 g/L. The diagnosis of pellagra disease was made. Vitamin and protein supplementation was initiated, but the patient committed suicide by puncture of her arteriovenous fistula, causing hemorrhagic shock. Pellagra is usually reported to be associated with malnutrition, chronic alcoholism, and some chemotherapeutic agents. In our patient, pellagra was caused by malnutrition and co-morbidities. Pellagra disease requires multidisciplinary care and can be frequently seen in HD patients due to the associated malnutrition.
Topics: Aged; Fatal Outcome; Female; Humans; Pellagra; Renal Dialysis; Renal Insufficiency, Chronic; Skin
PubMed: 32801252
DOI: 10.4103/1319-2442.292325 -
Journal of Cutaneous Medicine and... 2022
Topics: Humans; Pellagra
PubMed: 34494896
DOI: 10.1177/12034754211045378 -
Current Developments in Nutrition Sep 2019Vitamin deficiencies remain major etiological factors in the global burden of disease, especially in low- and middle-income countries. The purpose of this... (Review)
Review
Vitamin deficiencies remain major etiological factors in the global burden of disease, especially in low- and middle-income countries. The purpose of this state-of-the-art review was to update current information on deficiencies of vitamins and public health approaches to addressing them. Some stages of life present a higher risk of deficiency than others: risks are higher in pregnant women, children (from conception to young childhood), adolescents, the elderly, and all of the over 800 million people globally who are undernourished. At risk are approximately 125 million preschool children with vitamin A deficiency, as well as sub-populations at risk of deficiencies of folate, thiamin, vitamin B12, niacin, riboflavin, other B vitamins. and vitamin D. Addressing micronutrient deficiencies requires identifying those at risk and then working to prevent and manage that risk. Public health approaches include improved, diversified diets; supplementation; fortification and biofortification; and other supportive public health measures. Historically, as with pellagra and beriberi and, in the last 3 decades, with vitamin A and folic acid, there has been encouraging progress, but much remains to be done.
PubMed: 31598578
DOI: 10.1093/cdn/nzz075 -
Clinics in Dermatology 2021Epidemics of nutritional deficiency disorders, caused by a lack of vitamins and minerals, were once very common and claimed many victims. Fortunately, advances in...
Epidemics of nutritional deficiency disorders, caused by a lack of vitamins and minerals, were once very common and claimed many victims. Fortunately, advances in medicine have led to improved diets and a decline in the incidence of these disorders so that they are now seen clinically less often. Reminders of diseases such as scurvy, chlorosis, and pellagra can be found in artwork from the 19th century. The striking clinical presentation of these diseases caught the attention of artists who used them as themes in their work. We discuss the following three works of art: Gustave Doré's engraving for The Rime of the Ancient Mariner (plate 10), which features scurvy; Sebastian Junyent's painting Chlorosis; and Giuseppe Mentessi's painting Our Daily Bread, which portrays pellagra.
Topics: Anemia, Hypochromic; History, 19th Century; History, 20th Century; Humans; Paintings; Pellagra; Scurvy; Vitamins
PubMed: 34785013
DOI: 10.1016/j.clindermatol.2021.05.011