Introduction

Pellagra is a nutritional disorder caused by a deficiency of vitamin B3 complex (niacin) or the amino acid tryptophan, which is converted to niacin in the body. The name pellagra comes from ‘pelle agra’, an Italian term for rough skin. A minor deficiency of niacin may remain unnoticed, but a diet chronically low or without niacin may lead to the classical four Ds of pellagra (dermatitis, diarrhoea, dementia, and death). Pellagra may also cause gastrointestinal disturbances such as a sore tongue, nausea, vomiting, and sores in the mouth.¹

Causes of pellagra

The majority of the body’s niacin requirement is fulfilled by the dietary intake. The rest is fulfilled by synthesising niacin in the body from tryptophan. Niacin is found in many animal and plant products. A diet including milk, eggs, poultry, fish, legumes, and seeds etc, is sufficient to fulfill the daily dietary requirement of niacin and tryptophan.²

Pellagra is most common among the poor and people lacking enough food choices. It occurs due to:

• Insufficient intake of niacin or tryptophan in the diet
• The body's inability to absorb these nutrients
• Inadequate diet is the primary cause of pellagra
• Pellagra may also be a result of secondary causes such as pre-existing medical conditions that lead to niacin or amino acid deficiency. Some examples may be
  • Severe alcoholism
  • Crohn’s disease, and
  • Other vitamin B deficiencies
• Pellagra may also arise in patients with Hartnup disease, a genetic disorder where neutral amino acids such as tryptophan fail to get absorbed from the gastrointestinal tract

Pellagra is divided into two main types:

Primary pellagra

Primary pellagra is caused by a dietary deficiency of niacin in a poor population with limited access to food or people with nutritionally restrictive diets (eg, vegan diet) without diet support.

Secondary pellagra

Secondary pellagra occurs when your body is unable to absorb the niacin contained in the food consumed.

Symptoms of pellagra

Pellagra may lead to gastrointestinal, neurological, and dermatological issues. 

Gastrointestinal symptoms

• Diarrhoea is one of the early symptoms that develop in pellagra. Chronic or recurrent diarrhoea can lead to dehydration and can affect the absorption of nutrients from food leading to malnutrition. Diarrhoea can lead to watery stools which may occasionally be bloody and mucoid^3,4
• Nausea and vomiting may develop later
• Additional known gastrointestinal symptoms include anorexia, oesophagal burning, abdominal discomfort and distention, epigastric discomfort, and even constipation in some cases
• Anorexia and chronic malabsorptive diarrhoea may contribute to malnutrition and cachexia

Dermatological symptoms

• Dermatitis begins with the acute or intermittent onset of erythema (skin redness)^3,4
• Patients experience bilaterally symmetrical erythema at the sites of sun exposure which gradually changes to exudative eruption on
  • The dorsal of the hand
  • Face
  • Neck, and
  • Chest with pruritus and burning
• In the initial phases, acute dermatitis associated with pellagra resembles a sunburn, occasionally presenting with vesicles and bullae
• Dermatitis is present as a rash on the face, lips, feet, or hands
• In some cases, dermatitis can be seen around the neck, a symptom known as Casal necklace

Additional symptoms include:

• Red flaky skin
• Skin discolouration ranging from red to brown crusty
• Scaly, or cracked skin and skin thickening
• Angular cheilitis (cracking and inflammation of the corners of the mouth), and
• Redness and cracking in the corners of the eyelid

Neurological symptoms:

• Anxiety and depression are some of the early symptoms of pellagra
• Photophobia
• Asthenia
• Hallucinations
• Confusion
• Irritability
• Mood changes
• Memory loss and
• Psychosis
• Disease progression may lead to dementia, stupor, and death if pellagra is left untreated

Complications

• Untreated pellagra can lead to skin infection and nerve damage, particularly in the brain. In some cases, it may lead to death after 4 to 5 years
• Death in patients with pellagra can be a complication of severe malnutrition due to dietary deficiencies or infections, continuous diarrhoea, or neurological factors

Diagnosis

Diagnosis of pellagra can be challenging due to its wide array of symptoms. The diagnosis is based on the patient's clinical features and the presence of "3 D syndrome":^3,4

• Dermatitis
• Diarrhoea, and
• Dementia

Pathological changes in the skin are non-specific, and investigations such as blood tests, chemical tests, or skin biopsy may not be able to provide a definite diagnosis of pellagra but may be used to exclude other diagnoses.

However, urine tests indicating low levels of urinary excretion of N-methyl nicotinamide and pyridone may indicate niacin deficiency. Rapid response to niacin supplements may help confirm the diagnosis.

Treatment

Since pellagra is a deficiency of niacin (vitamin B3), treatment includes replacing the missing nutrient. With adequate supplements, most people begin to improve right away.

• In the case of primary pellagra, healthcare providers usually suggest maintaining a balanced diet. Niacin deficiency often occurs concomitantly with other micronutrient deficiencies. An adequate diet may effectively treat these deficiencies
• Nutrition education or additional support also helps
• Treating secondary pellagra can be trickier. Supplements often help, but they may not be enough to treat the deficiency if the body is unable to effectively metabolize niacin
• Recovery depends on treating the underlying condition which is causing pellagra. This process can be a long one, depending upon the condition
• While recovering from primary or secondary pellagra, additional treatment might be needed for dermatological symptoms. Skin rashes should be regularly moisturized and sunscreen should be used for protection against the sun

Prevention

The recommended daily dose of niacin is about 14 milligrams for women and 16 milligrams for men. A well-balanced diet ensures adequate nutrition and is the simplest way to prevent niacin deficiency. In case of limited food choices, dietary supplements may be helpful. For most healthy adults, vitamin B-complex supplements can provide adequate amounts of niacin. The best food sources of niacin are peanuts, potatoes, beets, rice, sunflower seeds, etc.

In people with chronic health conditions predisposing to pellagra, dietary supplements, changes in diet, and medication might help in the prevention of pellagra. However, any changes in diet or medication need to be discussed with healthcare providers.^5,6

Summary

Pellagra is a medical condition caused by the deficiency of niacin either due to malnutrition or malabsorption. It affects the skin, neurological system, and gastrointestinal system. Due to development in the food industry, this condition has become less common than it used to be. However, it is still a problem in many underprivileged and developing nations.

Pellagra is commonly divided into primary and secondary pellagra. While primary pellagra responds well to supplementation therapy and dietary changes, secondary pellagra may be difficult to treat based on the underlying cause. Patients with primary pellagra recover well within a few weeks of starting the treatment.

Common manifestations of this condition include dermatitis, diarrhoea, and dementia. If the condition is left untreated, it might result in death within 4 to 5 years. It is important to seek timely medical care to prevent complications associated with this condition.