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Postepy Dermatologii I Alergologii Aug 2022Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting... (Review)
Review
Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting various peptides or amines. These cells may be present in endocrine tissue or diffused in the tissues of the digestive or respiratory system. The article reviews the characteristic features of NENs, with particular emphasis on skin manifestations, such as necrolytic migratory erythema (NME), tongue inflammation, angular cheilitis, venous thrombosis and alopecia in glucagonoma; "flushing", "lion face", pellagra skin symptoms, "scleroderma-like features without Raynaud's phenomenon" in carcinoid tumours. The paper also presents the clinical picture of the neuroendocrine tumour of the skin - Merkel cell carcinoma. The aim of this study was to draw attention to the need for precise and comprehensive diagnosis of the patients, with particular emphasis on skin lesions as a revelator of neuroendocrine tumours. This management allows for the early implementation of appropriate treatment.
PubMed: 36090712
DOI: 10.5114/ada.2021.112073 -
Molecular Genetics and Metabolism Jun 2022The NAD(P)HX repair system is a metabolite damage repair mechanism responsible for restoration of NADH and NADPH after their inactivation by hydration. Deficiency in... (Review)
Review
The NAD(P)HX repair system is a metabolite damage repair mechanism responsible for restoration of NADH and NADPH after their inactivation by hydration. Deficiency in either of its two enzymes, NAD(P)HX dehydratase (NAXD) or NAD(P)HX epimerase (NAXE), causes a fatal neurometabolic disorder characterized by decompensations precipitated by inflammatory stress. Clinical findings include rapidly progressive muscle weakness, ataxia, ophthalmoplegia, and motor and cognitive regression, while neuroimaging abnormalities are subtle or nonspecific, making a clinical diagnosis challenging. During stress, nonenzymatic conversion of NAD(P)H to NAD(P)HX increases, and in the absence of repair, NAD(P)H is depleted, and NAD(P)HX accumulates, leading to decompensation; however, the contribution of each to the metabolic derangement is not established. Herein, we summarize the clinical knowledge of NAXE deficiency from 30 cases and lessons learned about disease pathogenesis from cell cultures and model organisms and describe a metabolomics signature obtained by untargeted metabolomics analysis in one case at the time of crisis and after initiation of treatment. Overall, biochemical findings support a model of acute depletion of NAD, signs of mitochondrial dysfunction, and altered lipidomics. These findings are further substantiated by untargeted metabolomics six months post-crisis showing that niacin supplementation reverses primary metabolomic abnormalities concurrent with improved clinical status.
Topics: Animals; Humans; Metabolic Diseases; NAD; NADP; Racemases and Epimerases
PubMed: 35637064
DOI: 10.1016/j.ymgme.2022.04.003 -
International Journal of Molecular... Apr 2022Immune 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... (Review)
Review
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.
Topics: COVID-19; Humans; NAD; Niacin; Niacinamide; Pellagra; SARS-CoV-2
PubMed: 35457123
DOI: 10.3390/ijms23084309 -
Bioscience of Microbiota, Food and... 2022Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We...
Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of this model is unclear. In this study, we found that the gut microbiota, which is thought to be a source of niacin, played an important role in the development of pellagra-related nausea in germ-free mice. We also investigated the gut microbiome. We compared urinary niacin metabolite levels and the dermal response between mice fed a normal diet and those fed a low-niacin diet to investigate the putative trigger of pellagra. Epoxyeicosatrienoic and hydroxyeicosatetraenoic acid levels were higher in mice fed a low-niacin diet compared with those fed a normal diet. Furthermore, histological studies indicated a dermatological response to the low-niacin diet. Interestingly, higher levels of oxidised fatty acids in response to the germ-free state were also observed. These findings indicate successful establishment of our newly established mouse model of pellagra via the gut microbiota. We believe that this model could enable the discovery of the putative cause of pellagra and phenotypes of pellagra that have not been recognised yet.
PubMed: 35433165
DOI: 10.12938/bmfh.2021-059 -
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 -
The Lancet. Global Health May 2022
Topics: Antitubercular Agents; Humans; Isoniazid; Pellagra
PubMed: 35427509
DOI: 10.1016/S2214-109X(22)00163-2 -
The Primary Care Companion For CNS... Mar 2022
Topics: Capgras Syndrome; Delusions; Ill-Housed Persons; Humans; Male; Pellagra; Schizophrenia
PubMed: 35276758
DOI: 10.4088/PCC.21cr03014 -
International Journal of Women's... Dec 2021This review article focuses on the dermatologic manifestations of selected nutrient deficiencies, including protein-energy and micronutrient-related malnutrition. The... (Review)
Review
This review article focuses on the dermatologic manifestations of selected nutrient deficiencies, including protein-energy and micronutrient-related malnutrition. The various nutrient deficiencies presented may share common features. However, distinctive cutaneous signs may prompt clinicians to consider a nutritional cause and help distinguish a nutrient deficiency from other common dermatologic conditions. The recent reemergence of forgotten nutritional deficiencies, such as scurvy and pellagra, in the context of predisposing risk factors that may uniquely affect women more than men makes this topic timely. Recognition of nutritional disorders is important because appropriate treatment may reverse cutaneous signs and prevent irreversible sequelae.
PubMed: 35024418
DOI: 10.1016/j.ijwd.2021.09.003 -
Folia Medica Cracoviensia Sep 2021Pellagra is a rare disease caused by niacin deficiency or a disruption of its metabolism. Its manifestations are dermatitis with pronounced photosensitivity,... (Review)
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.
Topics: Humans; Pellagra; Prevalence
PubMed: 34882669
DOI: 10.24425/fmc.2021.138956 -
Clinical Case Reports Oct 2021Pellagra is a clinical syndrome resulting from niacin deficiency with variety of manifestations. Azathioprine is among drugs that can lead to such condition. Physicians...
Pellagra is a clinical syndrome resulting from niacin deficiency with variety of manifestations. Azathioprine is among drugs that can lead to such condition. Physicians should be aware as proper management can lead to full resolution.
PubMed: 34703606
DOI: 10.1002/ccr3.4975