Pellagra and Niacin Deficiency
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Direct answer
Pellagra is niacin deficiency producing photosensitive dermatitis, diarrhoea and dementia, the three Ds, which progress to death if untreated. It follows maize-dependent diets low in bioavailable niacin and tryptophan, chronic alcoholism and malabsorption. Carcinoid syndrome, which diverts tryptophan into serotonin, and Hartnup disease, which blocks its absorption, are the classic causes that occur despite an adequate diet.
What you must remember
- Three Ds: dermatitis, diarrhoea and dementia, with death as the fourth D if untreated; this is the classic mnemonic examiners expect.
- Casal necklace: symmetrical pigmented dermatitis around the neck, named after the Spanish physician who described it, with sun-exposed areas typically involved.
- Dietary origin: maize contains niacin bound in a non-absorbable form unless alkali-treated, and it is poor in tryptophan, the body's other niacin source.
- Carcinoid: the tumour diverts tryptophan into serotonin, so pellagra occurs despite adequate dietary intake.
- Hartnup disease: an autosomal recessive defect in neutral amino acid transport causes tryptophan malabsorption, with a pellagra-like rash, cerebellar features and photosensitivity.
- Treatment: oral nicotinamide in high doses with a B-complex; nicotinic acid is less used because it causes intense flushing.
- Diagnosis: clinical, supported by low urinary N-methylnicotinamide, with a 24-hour urinary 5-HIAA estimation as the test that excludes carcinoid.
Worked example: a sunburn-like rash that is not sunburn
A 45-year-old man with alcohol dependence has a symmetrical red, scaly rash on the backs of both hands and the neck, glossitis, several weeks of watery diarrhoea and recent confusion.
- Note the photosensitivity. The rash worsens after sun exposure, which directs attention to photosensitive causes.
- Take a diet and alcohol history. The cluster of dermatitis, bowel and mental change fits niacin deficiency, so the pathway starts with a dietary and alcohol history.
- Check the other deficiencies. Liver function, folate, vitamin B12 and electrolytes are checked, and thiamine is given alongside because this patient is also at risk of Wernicke encephalopathy.
- Start high-dose nicotinamide. High-dose oral nicotinamide with a B-complex is started in divided doses, and sun protection is advised since light aggravates the rash.
- Consider the mimics. Porphyria and lupus must be considered for any photosensitive rash, so porphyrin testing is useful if the picture is atypical.
- Watch the recovery. The skin usually improves within days, while the diarrhoea and mental change take weeks.
- Exclude carcinoid if diarrhoea persists. In a non-drinker, a 24-hour urinary 5-HIAA test excludes carcinoid, since tumour-driven tryptophan diversion can produce the same picture.
Where the exam distinguishes the photosensitive causes
Pellagra is tested against other photosensitive rashes and against the other causes of niacin deficiency.
- Trap: picking porphyria or lupus because the rash is sun-triggered. Correct: pellagra adds diarrhoea and dementia to the rash, which makes the cluster distinctive.
- Trap: assuming maize cannot cause pellagra because it contains niacin. Correct: the niacin is bound, and alkali treatment releases it, which is why pellagra was historically linked to unprocessed maize diets.
- Trap: looking only at the niacin intake. Correct: tryptophan is the dietary precursor, and carcinoid and Hartnup disease are the two classic diversions that cause deficiency despite a normal diet.
Frequently asked questions
Which amino acid is the dietary precursor of niacin?
Tryptophan is the dietary precursor of niacin, with about 60 mg of tryptophan yielding roughly 1 mg of niacin. Pellagra can therefore develop when both preformed niacin and tryptophan intake are low, as in maize-dependent diets.
Why does a maize-based diet cause pellagra despite containing niacin?
Maize contains niacin in a bound, non-absorbable form and is also poor in tryptophan, so pellagra develops in populations relying on untreated maize. Alkali treatment releases the bound niacin and prevents the deficiency.
What is the Casal necklace?
Casal necklace is a symmetrical, pigmented dermatitis around the neck that is typical of pellagra, named after the Spanish physician who described it. It appears in sun-exposed areas and gives the characteristic collar-like pattern in an unexplained photosensitive rash.
Why is nicotinamide preferred over nicotinic acid in pellagra?
Nicotinamide is preferred in pellagra treatment because nicotinic acid causes intense flushing that limits its use. Both supply niacin for NAD and NADP synthesis, so nicotinamide corrects the deficiency with less discomfort for the patient.
Which investigation excludes carcinoid as the cause of pellagra?
A 24-hour urinary 5-HIAA estimation excludes carcinoid as the cause of pellagra, since carcinoid tumours overproduce serotonin and its breakdown product appears in urine. A raised result identifies the tryptophan diversion behind an otherwise unexplained case.