What Is Pellagra

Introduction

Pellagra is a nutritional deficiency disease caused by a deficiency of Niacin (a form of vitamin B3) and/or of its precursor tryptophan. Tryptophan is an amino acid that gets converted into niacin in the body. Pellagra is caused by having too little niacin or tryptophan in the diet or if the body fails to absorb these nutrients due to another health condition. Classically Pellagra manifests with a triad of symptoms of diarrhea, dermatitis, and dementia which can lead to a fatal outcome of Death if not detected and treated in time so it is also called a disease of 4 Ds.¹

History of Pellagra 

Pellagra was first described in 1735 by Casal in Spain by the term ‘mal de la rosa’ meaning the red disease.² In pellagra the skin exposed to sunlight becomes roughened in appearance like severe sunburn.

In 1771 Frapolli named the disease pellagra ³ for the most striking feature of the disease, which is rough skin, from the Italian ‘pelle’ for skin and ‘agra’ for rough thus rough skin.

In the early 19th century, Pellagra was a major problem in countries like southern Africa, the Mediterranean, and especially the southern USA where people relied heavily on maize as a staple food contributing to at least 250,000 cases and about 7,000 deaths a year in 15 southern states.⁴ Initially this was thought to be an infectious disease but the nutritional basis of the disease was established mainly by Goldberger and coworkers in the USA.⁵

Causes and risk factors 

1. Poor diet deficient in Niacin·       

• Lack of niacin and tryptophan-rich foods in diet such as meat, fish, poultry, nuts, and legumes
• Maize in untreated form is deficient in niacin and tryptophan, so if maize dominant diet is not balanced with other niacin-rich foods it leads to niacin deficiency⁶

2. Insufficient tryptophan conversion

·       

The liver uses tryptophan to produce niacin, for this process, the body needs enough Iron and Riboflavin. Conditions like iron deficiency anemia can lead to niacin deficiency⁷.

3. Conditions affecting nutrient absorption

• Certain gastrointestinal conditions like Crohn’s disease or ulcerative colitis can impair the absorption of niacin and tryptophan, leading to deficiency

• Chronic alcohol consumption can interfere with niacin absorption and metabolism, contributing to the development of pellagra in individuals with poor nutritional intake⁸ 

• Hartnup disease is a genetic disorder preventing your body from absorbing amino acids

 4. Other health conditions

• In Conditions like Carcinoid syndrome, and HIV infection niacin levels get depleted

• Chemotherapy or antispasmodic medications can disrupt your body’s niacin metabolism process

Signs and symptoms 

1. Dermatitis

Niacin deficiency affects skin cell metabolism making the skin sensitive to sunlight, so the areas exposed to sunlight become red, inflamed, itchy, and scaly in appearance. This typically occurs on the face, neck, arms, legs, hands, and feet. Over time the skin becomes thickened, hyperpigmented, and dark, and skin lesions can develop. There is an appearance of the characteristic feature of a ring of erythema and hyperpigmentation extending around the neck onto the chest called Casal’s necklace.⁹ 

2. Diarrhea  

It is common to experience increased bowel movements, watery stools with abdominal cramping, bloating, or gas due to an inflamed gastrointestinal tract. Inflammation and atrophy of the entire gastrointestinal tract results in a vicious cycle of nausea, loss of appetite, and watery diarrhea decreasing nutrient absorption.

3. Dementia 

A deficiency of Niacin and Tryptophan disrupts neurotransmitter synthesis and communication between nerve cells of the brain. This results in memory loss, confusion, disorientation, and forgetfulness. Mood disturbances, anxiety, emotional instability, and depression. If untreated it can worsen leading to confusion, delirium, and coma.¹⁰

4. Death

While death directly caused by pellagra is rare, untreated or severe pellagra can lead to various complications that may contribute to mortality, such as:

• Prolonged niacin deficiency can severely affect the liver. kidney and heart leading to organ damage or failure
• Untreated dementia, confusion, memory loss, and severe behavioral changes, may complicate brain functions leading to death
• Chronic diarrhea with dehydration and electrolyte imbalance can be life-threatening
• Weakened immune function, making individuals more susceptible to infections and other complications. This leads to dehydration and electrolyte imbalance and may turn into a serious condition if not treated on time

Investigations

Medical history and physical examination 

The healthcare provider will ask you about your dietary habits and symptoms and conduct a physical examination for any skin, gastro-intestinal, and neurological signs.

Blood tests

• Serum levels of  niacin and its metabolites
• Complete blood count (CBC) to check for anemia or other nutritional deficiencies
• Biochemical tests to assess liver and kidney function, electrolyte levels

Tryptophan levels

Assessment of tryptophan levels in the blood can help because it acts as a precursor to niacin and its deficiency can contribute to pellagra.

Skin biopsy

In cases of skin changes, a skin biopsy may be ordered for assessment.

Treatment 

1. Oral Niacin supplements

   Large amounts of niacin should be provided in the amide form which is called niacinamide or nicotinamide to avoid vasodilation (blood vessel dilating ) which causes skin flushing. Nicotinamide vitamin B3 supplements are widely available. It can be found either by itself or combined with other vitamins or minerals. The daily recommended intake is 100-300 mg of nicotinamide in divided doses. With niacin supplements, most people begin to improve right away but in chronic cases, a longer recovery period is required ¹¹

2. Vitamin B complex preparation 

   Conversion of Excess dietary tryptophan in Niacin requires the presence of vitamins B2 and B6. Thus it is recommended to administer a vitamin B complex preparation as well.

3. Dietary modifications

Meat, fish, Beef liver, Chicken breast, Tuna, Salmon, dry beans, nuts, and eggs are rich sources of niacin.  Bread, cereals, and rice fortified with niacin also contain good amounts of this vitamin.

 4. Symptomatic management 

• Avoid sun exposure and topical treatments such as sunscreens, moisturizers, or emollients to soothe and hydrate dry, irritated skin in dermatitis
• Take anti-diarrheal medications or oral rehydration solutions to manage diarrhea and prevent dehydration
• Take over-the-counter pain medications to alleviate abdominal pain or discomfort. If pain persists, it may be worth speaking to your doctor to see if you can get stronger pain relief prescribed by a healthcare professional
• Supportive care and psychological support or counseling to address mood swings, anxiety, or depression associated with pellagra-related neurological changes

FAQ

1. Who is most likely to get pellagra?

Pellagra is most common among poor populations where a nutritionally balanced diet is absent. The disease is more common in parts of the world like Africa, and Asia where untreated corn is a dominant portion of the diet as untreated corn is deficient in niacin. Pellagra is also seen in alcoholics because of interference in niacin absorption and nutritional imbalance. 

2. What is the necklace appearance in Pellagra?

The Casal collar or Casal necklace is a medical sign in which there is a redness and darkening of the skin around the neck, often seen in people with pellagra. 

3. Can pellagra be cured?

This condition is reversible with early intervention with niacin supplementation dietary modifications and treatment for management of symptoms. 

4. What are good sources of Niacin?

Meat, fish, Beef liver, Chicken breast, Tuna, Salmon, dry beans, nuts, and eggs are rich sources of niacin.  Bread, cereals, and rice fortified with niacin also contain good amounts of this vitamin.

Summary 

Pellagra is a nutritional deficiency disease caused by a lack of niacin (vitamin B3) and/or its precursor tryptophan. Tryptophan is an amino acid that gets converted into niacin in the body. Pellagra is caused by a deficiency of niacin or tryptophan in the diet or if the body fails to absorb these nutrients. Classically Pellagra manifests with a triad of symptoms of diarrhea, dermatitis, and dementia which can lead to fatal outcomes of death if not detected and treated in time so it is also called a disease of 4 Ds. Maize in untreated form is deficient in niacin and tryptophan. If a Maize dominant diet is not balanced with other niacin-rich foods it leads to niacin deficiency. Pellagra is diagnosed through clinical assessment and blood tests to confirm niacin deficiency. This condition is reversible with early intervention with niacin supplementation dietary modifications and treatment for management of symptoms.