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Pellagra

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Description: Pellagra is a nutritional disorder caused by a deficiency of niacin (vitamin B3) or its precursor tryptophan, leading to dermatitis, diarrhea, and dementia.
Type: Pellagra is a disease caused primarily by a deficiency of niacin (vitamin B3) and/or tryptophan. It is not primarily a genetic disorder but rather a nutritional deficiency, so it does not have a specific type of genetic transmission. However, secondary pellagra can result from conditions that interfere with the body's ability to convert tryptophan to niacin or absorb niacin, which may include some genetic disorders affecting metabolism.
Signs And Symptoms: The classic symptoms of pellagra are diarrhea, dermatitis, dementia, and death ("the four Ds").
A more comprehensive list of symptoms includes:

Sensitivity to sunlight
Dermatitis (characteristic "broad collar" rash known as casal collar)
Hair loss
Swelling
Smooth, beefy red glossitis (tongue inflammation)
Trouble sleeping
Weakness
Mental confusion or aggression
Ataxia (lack of coordination), paralysis of extremities, peripheral neuritis (nerve damage)
Diarrhea
Dilated cardiomyopathy (enlarged, weakened heart)
Eventually dementiaJ. Frostigs and Tom Spies—according to Cleary and Cleary—described more specific psychological symptoms of pellagra as:

Psychosensory disturbances (impressions as being painful, annoying bright lights, odors intolerance causing nausea and vomiting, dizziness after sudden movements),
Psychomotor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action), as well as
Emotional disturbancesIndependently of clinical symptoms, blood level of tryptophan or urinary metabolites such as 2-pyridone/N-methylniacinamide ratio <2 or NAD/NADP ratio in red blood cells can diagnose pellagra. The diagnosis is confirmed by rapid improvements in symptoms after doses of niacin (250–500 mg/day) or niacin enriched food.
Prognosis: The prognosis for pellagra largely depends on early diagnosis and prompt treatment. If diagnosed and treated early with adequate niacin (vitamin B3) supplementation and dietary improvements, the prognosis is generally good, and most patients recover fully. However, if left untreated, pellagra can lead to severe complications and can be fatal. Chronic cases can result in persistent skin issues, neurological problems, and gastrointestinal symptoms. Early medical intervention is crucial for a favorable outcome.
Onset: Pellagra typically develops gradually, with symptoms arising after several months of niacin (vitamin B3) deficiency. Initial symptoms might include loss of appetite, weakness, and digestive disturbances, progressing to the classic triad of dermatitis, diarrhea, and dementia if untreated.
Prevalence: The prevalence of pellagra, a disease caused by niacin (vitamin B3) deficiency, has significantly decreased in developed countries due to improved nutrition. However, it still occurs in some developing regions where corn-based diets are prevalent and there is limited access to a diverse food supply. Exact prevalence numbers are not readily available, but the condition is more common in areas experiencing food scarcity or where maize constitutes a staple food without proper fortification or preparation methods.
Epidemiology: Pellagra can be common in people who obtain most of their food energy from corn, notably rural South America, where maize is a staple food. If maize is not nixtamalized, it is a poor source of tryptophan, as well as niacin. Nixtamalization corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn, but most especially in Mexico and the countries of Central America. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, such as Mississippi and Alabama, where its cyclical appearance in the spring after meat-heavy winter diets led to it being known as "spring sickness" (particularly when it appeared among more vulnerable children), as well as among the residents of jails and orphanages as studied by Dr. Joseph Goldberger.Pellagra is common in Africa, Indonesia, and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol-dependent, or psychiatric patients who refuse food. Pellagra was common among prisoners of Soviet labor camps (the Gulags). In addition, pellagra, as a micronutrient deficiency disease, frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely on limited sources of niacin provided to them, often peanuts (which, in Africa, may be supplied in place of local groundnut staples, such as the Bambara or Hausa groundnut); the instability in the nutritional content and distribution of food aid can be the cause of pellagra in displaced populations. In the 2000s, there were outbreaks in countries such as Angola, Zimbabwe and Nepal. In Angola specifically, recent reports show a similar incidence of pellagra since 2002, with clinical pellagra in 0.3% of women and 0.2% of children and niacin deficiency in 29.4% of women and 6% of children related to high untreated corn consumption.In other countries such as the Netherlands and Denmark, even with sufficient intake of niacin, cases have been reported. In this case, deficiency might happen not just because of poverty or malnutrition but secondary to alcoholism, drug interaction (psychotropic, cytostatic, tuberculostatic or analgesics), HIV, vitamin B2 and B6 deficiency, or malabsorption syndromes such as Hartnup disease and carcinoid tumors.
Intractability: Pellagra is not considered an intractable disease. It is caused by a deficiency of niacin (vitamin B3) or its precursor tryptophan. Treatment involves dietary supplementation of niacin and addressing underlying causes of the deficiency. With appropriate intervention, symptoms can be effectively managed and reversed.
Disease Severity: Pellagra is a potentially severe disease caused by a deficiency of niacin (vitamin B3) or its precursor tryptophan. If left untreated, it can be life-threatening.
Healthcare Professionals: Disease Ontology ID - DOID:8457
Pathophysiology: Pellagra can develop according to several mechanisms, classically as a result of niacin (vitamin B3) deficiency, which results in decreased nicotinamide adenine dinucleotide (NAD). Since NAD and its phosphorylated NADP form are cofactors required in many body processes, the pathological impact of pellagra is broad and results in death if not treated.
The first mechanism is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan, an essential amino acid found in meat, poultry, fish, eggs, and peanuts, which the body uses to make niacin. Third, it may be caused by excess leucine, as it inhibits quinolinate phosphoribosyl transferase (QPRT) and inhibits the formation of niacin or nicotinic acid to nicotinamide mononucleotide (NMN) causing pellagra-like symptoms to occur.Some conditions can prevent the absorption of dietary niacin or tryptophan and lead to pellagra. Inflammation of the jejunum or ileum can prevent nutrient absorption, leading to pellagra, and this can in turn be caused by Crohn's disease. Gastroenterostomy can also cause pellagra. Chronic alcoholism can also cause poor absorption, which combined with a diet already low in niacin and tryptophan produces pellagra. Hartnup disease is a genetic disorder that reduces tryptophan absorption, leading to pellagra.
Alterations in protein metabolism may also produce pellagra-like symptoms. An example is carcinoid syndrome, a disease in which neuroendocrine tumors along the GI tract use tryptophan as the source for serotonin production, which limits the available tryptophan for niacin synthesis. In normal patients, only one percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this value may increase to 70%. Carcinoid syndrome thus may produce niacin deficiency and clinical manifestations of pellagra. Anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction.
Several therapeutic drugs can provoke pellagra. These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis, and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine.
Carrier Status: Pellagra is not a condition associated with a carrier status or genetic inheritance. It is a disease caused primarily by a deficiency of niacin (vitamin B3) or its precursor, tryptophan. The primary risk factors for pellagra include inadequate dietary intake of niacin and certain medical conditions that affect nutrient absorption.
Mechanism: Pellagra is a disease caused by a deficiency of niacin (vitamin B3) and its precursor, tryptophan.

**Mechanism:**
- Insufficient intake or absorption of niacin or tryptophan leads to decreased synthesis of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
- NAD and NADP are essential coenzymes in various metabolic processes, including oxidative reactions and the synthesis of fatty acids and steroids.

**Molecular Mechanisms:**
- Niacin is a precursor to NAD and NADP. Without adequate niacin, cells cannot produce sufficient amounts of these crucial coenzymes.
- NAD is involved in redox reactions (electron transport chain, glycolysis, and the Krebs cycle), DNA repair, and gene expression regulation.
- The deficiency hampers cellular metabolism, leading to clinical manifestations such as dermatitis, diarrhea, dementia, and ultimately death if untreated.

In summary, pellagra results from disrupted metabolic processes due to the lack of NAD/NADP, primarily impacting enzymatic functions and energy production.
Treatment: If untreated, pellagra can kill within four or five years. Treatment is with nicotinamide, which has the same vitamin function as niacin and a similar chemical structure, but has lower toxicity. The frequency and amount of nicotinamide administered depends on the degree to which the condition has progressed.
Compassionate Use Treatment: Pellagra is primarily caused by a deficiency of niacin (vitamin B3) and is typically treated with niacin supplementation and dietary modifications. In terms of compassionate use, off-label, or experimental treatments, these are generally less common given the effective standard treatment. However, in cases where traditional niacin supplementation is not effective or feasible, there are few noted alternatives:

1. **Nicotinamide**: Some patients may use nicotinamide (a form of vitamin B3) as it has similar effects to niacin but does not cause the flushing side effect.
2. **Tryptophan supplementation**: Since the body can synthesize niacin from the amino acid tryptophan, tryptophan supplements could theoretically be considered, although this approach is not commonly documented.
3. **High-dose multivitamins**: Occasionally, high-dose multivitamin preparations that include niacin and other B vitamins might be recommended.

It's crucial to consult healthcare professionals for personalized treatment plans, especially when considering off-label or experimental treatments.
Lifestyle Recommendations: For pellagra:

**Lifestyle Recommendations:**
1. **Dietary Changes:** Increase the intake of niacin-rich foods such as lean meats, fish, poultry, peanuts, and whole grains. Additionally, foods high in tryptophan, like dairy products, eggs, and certain seeds, can help since the body converts tryptophan to niacin.
2. **Alcohol Consumption:** Limit or avoid alcohol, as excessive consumption can hinder the absorption of niacin.
3. **Balanced Diet:** Ensure a well-balanced diet that provides adequate levels of essential vitamins and minerals to avoid malnutrition.
4. **Supplementation:** If dietary intake is insufficient, consider niacin supplements under medical guidance.
5. **Healthcare Follow-Up:** Regularly consult with a healthcare provider to monitor and manage the condition effectively.

**Nan:** The term "nan" needs clarification. If referring to a specific aspect or query regarding pellagra, please provide additional context.
Medication: Pellagra is primarily treated with supplementation of niacin (vitamin B3) and other B-complex vitamins. Treatment may include:

- **Niacin (Nicotinic acid or Niacinamide):** Administered in doses typically ranging from 300 to 500 mg per day, divided into smaller doses.
- **Multivitamins:** To address potential deficiencies of other B vitamins.
- **Dietary Changes:** Improving the diet to include niacin-rich foods such as meat, fish, poultry, and fortified grains. In cases where the condition is secondary to malabsorption disorders or alcoholism, additional interventions to address the underlying cause may be necessary.
Repurposable Drugs: For the treatment of pellagra, repurposable drugs include:

1. **Niacin (Vitamin B3)** - The most direct and effective treatment, as pellagra is primarily caused by a deficiency of niacin.
2. **Nicotinamide** - Another form of Vitamin B3 that is often used interchangeably with niacin to treat pellagra.

No additional repurposable drugs are commonly noted specifically for pellagra, as addressing the niacin deficiency directly is generally sufficient. If concurrent symptoms or complications are present, treatments might need to be adjusted accordingly.
Metabolites: For pellagra, the key metabolite involved is **nicotinamide adenine dinucleotide (NAD+).** Pellagra is primarily caused by a deficiency of niacin (vitamin B3) or tryptophan, which are precursors for the synthesis of NAD+. This metabolite is crucial for various cellular processes, including redox reactions and energy metabolism. The deficiency of NAD+ leads to the clinical manifestations of pellagra, which include dermatitis, diarrhea, dementia, and if left untreated, can be fatal.
Nutraceuticals: Pellagra is primarily caused by a deficiency of niacin (vitamin B3) or its precursor tryptophan. Nutraceuticals that can help in the management and prevention of pellagra include:

1. **Niacin Supplements**: Direct supplementation with niacin (nicotinic acid) can effectively address the deficiency.
2. **Niacinamide**: This form of vitamin B3 is an alternative to niacin and can also help treat pellagra.
3. **Tryptophan-Rich Supplements**: Since tryptophan is a precursor to niacin, supplements containing this amino acid can be beneficial.
4. **Multivitamins**: Comprehensive multivitamin supplements that include B-complex vitamins may aid in preventing deficiencies.

Nanotechnology-based treatments are currently not standard for pellagra. However, research is ongoing in the field of nanomedicine to explore targeted delivery systems for various nutrients, which could potentially enhance the bioavailability and efficacy of niacin supplementation in the future.
Peptides: For pellagra:

- Peptides: Pellagra is primarily caused by a deficiency in niacin (vitamin B3) or its precursor, tryptophan. Peptides and proteins that contain tryptophan can be utilized by the body to produce niacin, thereby preventing or alleviating the symptoms of pellagra.

- Nan: This term is unclear in this context. If "nan" refers to a misinterpretation or a typographical error, additional clarification would be needed. If it stands for something specific (like nanocarriers in drug delivery), please provide more context.