Pellagra in Zanzibar: a rare diagnosis.

BACKGROUND: Pellagra is a nutritional disease resulting from a deficiency of vitamin B3 (niacin) primarily due to corn consumption, especially in developing countries, but in developed countries, it can occur secondarily as a consequence of chronic alcoholism, malabsorption, certain drugs, and bariatric surgery. RESULTS: We present a case of a 32-year-old woman from a rural area in Zanzibar who was a heavy alcohol consumer and came in with features suggestive of pellagra. CONCLUSION: Our therapeutic approach consisted of niacin 500 mg once daily and betamethasone + salicylic acid ointment twice a day until lesions resolved and showed noticeable improvement.

Pellagra as a differential diagnosis in the confused patient on the acute medical unit.

A man in his 80s was admitted via the acute medical take after presenting with increased confusion and features of alcohol withdrawal. He had a several-month history of a worsening pruritic rash surrounding his neck, arms and legs in addition to new, profuse diarrhoea. In view of the background of known chronic alcoholism and the coexisting symptoms of rash, confusion and diarrhoea, pellagra was diagnosed via a multidisciplinary approach. Oral nicotinamide supplementation was commenced and his symptoms responded rapidly. The bias and challenge of reaching a unified diagnosis in the context of a multisystem condition are exemplified in this case report.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

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.

COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?

Immune response to SARS-CoV-2 and ensuing inflammation pose a huge challenge to the host's nicotinamide adenine dinucleotide (NAD+) metabolism. Humans depend on vitamin B3 for biosynthesis of NAD+, indispensable for many metabolic and NAD+-consuming signaling reactions. The balance between its utilization and resynthesis is vitally important. Many extra-pulmonary symptoms of COVID-19 strikingly resemble those of pellagra, vitamin B3 deficiency (e.g., diarrhoea, dermatitis, oral cavity and tongue manifestations, loss of smell and taste, mental confusion). In most developed countries, pellagra is successfully eradicated by vitamin B3 fortification programs. Thus, conceivably, it has not been suspected as a cause of COVID-19 symptoms. Here, the deregulation of the NAD+ metabolism in response to the SARS-CoV-2 infection is reviewed, with special emphasis on the differences in the NAD+ biosynthetic pathway's efficiency in conditions predisposing for the development of serious COVID-19. SARS-CoV-2 infection-induced NAD+ depletion and the elevated levels of its metabolites contribute to the development of a systemic disease. Acute liberation of nicotinamide (NAM) in antiviral NAD+-consuming reactions potentiates "NAM drain", cooperatively mediated by nicotinamide N-methyltransferase and aldehyde oxidase. "NAM drain" compromises the NAD+ salvage pathway's fail-safe function. The robustness of the host's NAD+ salvage pathway, prior to the SARS-CoV-2 infection, is an important determinant of COVID-19 severity and persistence of certain symptoms upon resolution of infection.

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.

Pelagra: una enfermedad antigua en un mundo moderno / Pellagra: an ancient disease in a modern world

Introducción: la pelagra es una enfermedad sistémica secundaria a la deficiencia de vitamina B3 o de su precursor, el triptófano. La vitamina B3 es necesaria para varios procesos metabólicos, de señalización celular y reparación del ADN. Se caracteriza por la tétrada clásica de dermatitis, diarrea, demencia y muerte. La misma es considerada una enfermedad rara hoy en día; sin embargo, con el auge de las dietas restrictivas sin la adecuada suplementación, como es el caso del veganismo, se ha visto un aumento de los casos en los últimos años. Caso clínico: exponemos el caso de una paciente adulta joven, vegana estricta, a la cual se le realizó el diagnóstico de pelagra y se le instauró un tratamiento de forma precoz, con una excelente evolución. Discusión: el interés del caso radica en la importancia de la sospecha clínica y la anamnesis dirigida a factores sociales y nutricionales, adaptados a la época actual, para poder hacer el diagnóstico de una enfermedad rara e infradiagnosticada que es potencialmente mortal de retrasarse el inicio del tratamiento. (AU)

Background: pellagra is a systemic disease due to deficiency of vitamin B3 or tryptophan, its precursor. Vitamin B3 is needed for several metabolic processes, cell signaling, and DNA repair. It is characterized by a classic tetrad of dermatitis, diarrhea, dementia, and death. Pellagra is considered rare nowadays; however, due to the popularity of restrictive diets without necessary supplementation such us veganism, there has been an increase in cases in recent years. Case report: we report the case of a young strict vegan female patient in which a pellagra diagnosis was made, and early treatment was administered with an excellent outcome. Discussion: the interest of this case lies in the importance of clinical suspicion and directed history taking focused on social and nutritional factors, as adapted for the current times, in order to make the diagnosis of a rare, subdiagnosed disease that is life-threatening if treatment is delayed. (AU)

Chronic Diarrhea in a Drinker: A Breakthrough Case of Pellagra in the US South.

The triad of diarrhea, dementia, and dermatitis constitutes the clinical diagnosis of pellagra. However, most reported cases of pellagra have occurred without all components of the triad. Pellagra was declared eradicated in the United States after an outbreak in the 1920s, and is now considered to be an exceedingly rare diagnosis in developed countries. In this article, we present a case of a 56-year-old man who presented with a significant history of alcohol use and chronic diarrhea. Pellagra was clinically diagnosed based on the triad of diarrhea, cognitive dysfunction, and dermatitis in this malnourished, alcoholic patient. The patient was treated and clinically improved with resolution of his diarrhea and cognitive dysfunction.

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, an Almost-Forgotten Differential Diagnosis of Chronic Diarrhea: More Prevalent Than We Think.

Pellagra, caused by vitamin B3 (niacin) deficiency, is traditionally described as dermatitis, diarrhea, dementia (3D), and even death (4D) syndrome if not recognized and treated promptly. Although full-blown pellagra with all 3D features has become rare, pellagra still exists, especially in high-risk populations, which is actually more prevalent than we think. We report that a recently treated patient with the full spectrum of 3D clinical features of pellagra presents as chronic diarrhea of unknown etiology for 1 year. It reminds us that keeping a high index of suspicion and maintaining a broad differential diagnosis are critical for recognition and management of this potentially fatal but treatable condition.

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.