Pellagra

What is Pellagra?

• Pellagra is a disease caused by deficiency of vitamin B3 (niacin) in the diet. Niacin is required for several important cellular processes.
• It is derived from the diet or by conversion of amino acid tryptophan to niacin in the body.
• Since tryptophan can be converted to niacin in the body, it must also be deficient in the diet in order for the disease to manifest.
• The four characteristic features of pellagra appear as dermatitis, diarrhea and dementia ("the three Ds") and can lead to death (the fourth D).

Epidemiology of Pellagra

Pellagra used to be common before foods were fortified with niacin. Nowadays it is seen only sporadically and especially in countries where diet is mainly corn based such as Africa, China and India.

Recommended Daily Allowance (RDA) of Niacin

The World Health Organization (WHO) recommendation of niacin for adults of all ages is 6.6 niacin equivalents per 1000 kcal and not less than 13 niacin equivalents (NE) at caloric intakes of less than 2000 kcal. The stipulated 6.6 niacin equivalents per 1000 kcal daily is also recommended for children of 6 months or older.

One NE equals 1 mg niacin or 60 mg tryptophan.

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What are the Causes/Risk Factors of Pellagra?

The single-most major risk factor for niacin deficiency is the consumption of maize. People who rely solely on maize as a staple food in their diet are particularly at risk of pellagra. Importantly, corn is also low in niacin and tryptophan. Alcohol can aggravate the symptoms of pellagra and lead to complications. Patients on antibiotics like isoniazid and rifampicin, as well as diabetic patients are at a higher risk of niacin deficiency.

Pellagra can be of two types, based upon the cause. These are primary and secondary pellagra. Primary pellagra is caused by deficiency of niacin and tryptophan in the diet. Secondary pellagra is caused by the inability to absorb and process the niacin present in the diet. The major causes of secondary pellagra include the following:

• Chronic alcoholism
• Fad diets
• Chronic diarrhea
• Hartnup disease
• Cirrhosis of the liver
• Carcinoid tumors - tryptophan is mainly converted to serotonin (and not niacin)
• Gastrointestinal diseases
• Drugs such as isoniazid, rifampicin and azathioprine

What are the Symptoms and Signs of Pellagra?

General symptoms of pellagra include loss of appetite, anorexia nervosa, weakness and fatigue, and tongue inflammation (beefy red tongue). The cardinal features of pellagra include a triad of symptoms involving the skin, gastrointestinal tract and the nervous system. These are briefly highlighted below:

Dermatological Symptoms:

The dermatological symptoms are the most prominent in pellagra. Reddening of the skin resembling a sunburn (sun allergy) occur on the exposed parts of the body. These include the hands and forearms up to the shirt sleeves that resembles a glove (termed “pellagra gloves”). Other parts include the feet and legs, the forehead, and on the nose and cheeks in a butterfly-like pattern. A characteristic pattern of lesion resembling a necklace, termed as Casals necklace, can be seen around the neck.

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Pellagra dermatitis is characterized by a clear zone of demarcation between the affected and normal skin. The erythema is accompanied by burning and itching sensation; scaling and exfoliation can begin from the centre of the lesion and spread towards the periphery. The affected skin is usually hyperpigmented.

The skin may become thickened, scaly, and cracked, through which blood may ooze. Skin lesions on the surface of the lips, gums and tongue can become sore and start to peel. Importantly, the skin lesions affecting the scalp can result in alopecia.

Gastrointestinal Symptoms:

Over half of the patients who suffer from pellagra experience severe diarrhea. Inflammation along the entire gastrointestinal (GI) tract, resulting in chronic gastritis, and accompanied by bacterial infections, can aggravate the diarrhea and also cause anemia. Abdominal cramps, burning sensation above the stomach (resembling “heartburn”), excessive salivation, nausea and vomiting can occur.

Poor appetite, coupled with difficulty in swallowing can lead to malnutrition. Cheilosis and angular stomatitis can also be seen in niacin deficiency.

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Neurological Symptoms:

The initial stages exhibit a psychoneurotic manifestation. These can manifest as irritability, insomnia, confusion, disorientation, anxiety, delusions, depression, and psychosis.

In the later stages, mental aberrations may undergo a transition to dementia. Research studies have found that about 4-10% of chronic pellagra patients develop mental symptoms. Peripheral neuritis has been reported in some pellagra cases. Other symptoms include headache, ataxia, and even paralysis. In acute niacin deficiency an encephalopathy is found which closely resembles Wernicke's syndrome.

In the terminal stage, the patient can slip into coma, and if left untreated, can eventually die.

How do you Diagnose Pellagra?

The main criteria for diagnosing pellagra include the following:

Patient history can reveal a dietary deficiency of niacin and tryptophan, a precursor of nicotinic acid.

Clinical manifestations characteristic of pellagra include the following:

• Skin: Initially the skin becomes red and resembles a sunburn. This is followed by hyperpigmentation and thickening. Bilateral and symmetrical lesions occur in areas of friction and exposure, such as the face, neck, hands, and feet, with a clear demarcation of the lesions from normal skin.
• Mouth: Gingivitis, angular stomatitis and a fiery glossitis can occur. The tongue becomes swollen with a beefy red appearance.
• GI Tract: Diarrhea is the predominant feature.
• Central Nervous System: Progressive dementia occurs, with apprehension and confusion in the early stages, which progresses to severe derangement with manic phases.

Blood and urine tests can support the clinical observations and clinch the diagnosis of pellagra. Low levels of serum niacin, tryptophan, NAD, and NADP can indicate niacin deficiency. Estimation of the levels of urinary excretion of products of niacin metabolism, primarily N1-methylnicotinamide (N1-MN) and 2-pyridone, can reflect the status of niacin in the body.

How do you Treat Pellagra?

• The administration of niacin has a dramatic curative impact on pellagra.
• The daily recommended dose is 300 mg of nicotinamide in divided doses, and treatment should continue for 3-4 weeks. High therapeutic doses of niacin should be provided in the form of nicotinamide. Acute inflammation of the tongue and mouth, as well as diarrhea, subside in a few days. The dementia and dermatitis usually improve significantly within the first week of therapy.
• In chronic cases, a longer recovery period is required, but appetite and general physical health improve rapidly.
• Administration of vitamin B-complex is recommended since patients with pellagra are usually deficient in other B vitamins also.
• A diet rich in proteins is also recommended for complete recovery. Skin irritation and lesions can be treated with antibacterial ointments to prevent any superficial infections.
• Emollients can be applied to soothe the skin. During the recovery phase, exposure to sunlight must be avoided at all costs. Sunscreen lotions should be applied to all exposed parts of the body to prevent sun allergy.

How do you Prevent Pellagra?

The under-mentioned strategies can be adopted for the prevention of pellagra:

Consumption of a Balanced Diet: A balanced diet is the most effective way to prevent niacin deficiency, as well as that of other vitamins in the B-complex class. The following foods are particularly rich sources of the B-complex class of vitamins: fish, chicken, beef liver, milk and milk products, beans, and fortified soy milk.

Food Fortification: When the major staple food is maize (which lacks niacin), there is a need for fortification of the maize meal with niacin.

Vitamin Supplementation: Provision of niacin in the form of vitamin B-complex tablets is required for prevention and treatment of pellagra.

What are the Complications of Pellagra?

The major complications of pellagra are neuropsychiatric in nature such as dementia, which can quickly slip into coma and if left untreated, will eventually lead to death.