Pellagra

Pellagra results from the deficiency of niacin (vitamin B3). It was first described by Don Casal a Spanish court physician in the 1700s where thickened skin was noted in peasants. However, it was not until the 1900s that the cause and treatment of pellagra was determined.

• Vitamin B deficiency is rare in the UK.
• Prior to food fortification with niacin epidemics of pellagra were seen. However, sporadic cases are still occasionally seen.
• Niacin deficiency is seen in the following groups
  • Diets based mainly on corn (low in tryptophan and niacin) e.g. China, Africa and India.
  • Alcoholics - usually deficient in other vitamins also.
  • Eating disorders e.g. anorexia nervosa.¹
  • Hartnup's disease - congenital malabsorption of tryptophan from the intestine and kidney.
  • Carcinoid syndrome - tryptophan is increasingly converted to serotonin.

There is concern that the number of cases of pellagra are likely to increase with increasing fad diets.²

Classically described as 3 Ds

• Dementia
• Diarrhoea
• Dermatitis

Some add a fourth D - Death.

Early symptoms include:

• Loss of appetite
• Generalised weakness
• Irritability and aggression
• Abdominal pain
• Vomiting

Continued deficiency leads to epithelial changes leading to:

• Stomatitis
• Bright red glossitis
• Vaginitis
• Oesophagitis
• Dermatitis - classically a pigmented, scaly rash prominent in sun exposed skin e.g. back of the hand called "gauntlet" of pellagra or on the neck where it can form a ring called "Casal's" necklace. The rash begins as itchy erythema and then looks similar to a tan and may vesiculate.³

Other features include:

• Diarrhoea - due to a combination of proctitis and malabsorption.
• Dementia - may present as depression, followed by memory deficits and hallucinations or psychosis may occur.
• Seizures
• Paraesthesia may occur
• Malabsorption

After niacin has been processed it can be excreted in the urine. The products detected in the urine include nicotinic acid, niacin oxide and metabolites including 2-pyridone and 2-methyl nicotinamide.

The latter two metabolites can be measured to assess niacin deficiency (low levels will be present).

RBC levels of NAD/NADP can also be useful in the diagnosis.

• Oral supplementation with nicotinamide is usually used (e.g 100 - 200 mg three times a day until symptoms remit).
• Nicotinamide is used in preference to nicotinic acid as side effects relating to vasodilatation are less e.g. flushing.⁴
• Cutaneous lesions begin to resolve in 24 - 48 hours after starting treatment.

Adverse effects of treatment

• Nausea, vomiting and abdominal pain
• Dry skin and pruritus
• Headache
• Flushing - mediated by prostaglandin release and seen with high doses of nicotinic acid e.g. above 50 mg per day.
• Glucose intolerance
• Macular oedema and cysts
• Hepatotoxicity - very rarely jaundice with a rise in transaminases is seen. Fulminant hepatitis has been reported with very high doses (>3 gm per day).

High doses of nicotinic acid (>3 gm per day) are used in the treatment of certain types of hyperlipidaemias (it lowers both cholesterol and triglycerides) and toxic effects such as flushing and hepatotoxicity are seen more frequently at these dose ranges.

No toxic effects are seen with food sources of niacin.

It is unclear whether sustained forms of nicotinic acid are associated with more or less toxicity.

Prompt diagnosis and treatment of cases leads to an excellent recovery.
Prevention involves adequate niacin intake and dietary advice to vulnerable groups e.g. pregnant women.