Pellagra (Niacin Deficiency)

What niacin does

Niacin (nicotinic acid and nicotinamide) is used to make NAD and NADP, coenzymes essential for energy production in every cell. The body can also make niacin from the amino acid tryptophan. Tissues with high energy turnover and rapid cell renewal, such as the skin, gut lining and brain, are most affected by deficiency.

Good food sources include meat, poultry, fish, peanuts, legumes, whole and enriched grains, and dairy and eggs (rich in tryptophan).

Why pellagra happens

Primary (dietary) pellagra

• diets based on untreated corn (maize), whose niacin is bound and poorly absorbed; traditional treatment with lime (nixtamalization), as in making tortillas, releases it
• famine, refugee settings and extreme poverty
• restrictive diets and eating disorders

Secondary pellagra

• alcohol use disorder: the most common cause in high-income countries, due to poor diet and impaired absorption
• malabsorption: Crohn's disease, chronic diarrhea, bariatric surgery
• carcinoid syndrome: tumors divert tryptophan to serotonin
• medicines: isoniazid (for tuberculosis), some anti-seizure drugs, azathioprine, 5-fluorouracil
• Hartnup disease: a rare inherited problem absorbing tryptophan
• long-term dialysis and HIV

Symptoms: the 4 Ds

Dermatitis

• a symmetric, sharply bordered rash on sun-exposed skin: backs of hands, forearms, face and neck
• starts red and burning like sunburn, then becomes dark, rough, thick and scaly
• Casal's necklace: a band around the neck
• sometimes blistering and cracking

Diarrhea and gut symptoms

• diarrhea, nausea, vomiting and abdominal pain
• red, swollen, sore tongue (glossitis) and mouth ulcers
• poor appetite and weight loss

Dementia and nervous system symptoms

• early: fatigue, irritability, anxiety, depression, poor concentration, insomnia
• later: confusion, memory loss, disorientation, hallucinations, psychosis
• tremor, poor coordination, nerve damage

Death

Untreated advanced pellagra is fatal within a few years.

Not all features are always present. People with alcohol use disorder may show mainly confusion, and pellagra can coexist with thiamine deficiency (Wernicke's encephalopathy).

Diagnosis

Pellagra is diagnosed mainly from the typical symptoms in someone at risk and a rapid response to niacin. Supporting tests:

• urine levels of niacin breakdown products (such as N-methylnicotinamide)
• blood NAD levels where available
• tests for other nutritional deficiencies, which often coexist
• skin biopsy if the rash is unclear
• tests for underlying causes, such as carcinoid syndrome

Treatment

• niacinamide (nicotinamide) is preferred because it does not cause flushing; given by mouth under medical supervision
• treating other deficiencies, especially thiamine, B6, zinc and protein
• a balanced, protein-rich diet
• sun protection for the rash
• treating the underlying cause: alcohol treatment, managing malabsorption, adjusting medicines

Recovery timeline

• mental symptoms often improve within 24 to 48 hours
• diarrhea and mouth soreness improve over days
• skin heals over 2 to 4 weeks, though dark discoloration can last longer

Prevention

• a varied diet including protein sources
• enriched flour and cereals (used in the US since the 1940s, which nearly eliminated pellagra)
• vitamin supplementation for people at risk, such as those with alcohol use disorder, on isoniazid, or with malabsorption

Frequently asked questions

What are the 4 Ds of pellagra?

The 4 Ds are dermatitis (a sun-sensitive, dark, scaly rash), diarrhea, dementia (confusion, memory and mood changes) and death if untreated. Not everyone has all four, and mental changes may appear first.

What causes pellagra?

Pellagra is caused by a severe lack of niacin or tryptophan. Today it mostly occurs with alcohol use disorder, malabsorption, eating disorders, some medicines like isoniazid, carcinoid syndrome, or diets based on untreated corn.

What does the pellagra rash look like?

It is a symmetric rash on sun-exposed skin, like the backs of the hands, forearms, face and neck. It starts red and burning, then turns dark, thick, rough and scaly. A band around the neck is called Casal's necklace.

How is pellagra treated?

Pellagra is treated with niacinamide supplements, a nutritious diet, treatment of other vitamin deficiencies and of the underlying cause. Mental symptoms often improve within a day or two, and the rash heals over a few weeks.

Is pellagra still common?

It is rare in high-income countries because of food fortification, but still occurs in people with alcohol use disorder, malabsorption or restrictive eating. It remains a problem in some low-income regions and humanitarian emergencies.