Pellagra: Niacin Deficiency — Causes, Symptoms & Treatment

Pellagra is a systemic disease caused by deficiency of niacin (vitamin B3) or its precursor tryptophan. Classic presentation: the "3 Ds" — Dermatitis, Diarrhea, Dementia; untreated → Death (4th D).

Etiology

Primary (Dietary)

• Maize (corn)-based diets without nixtamalization (alkali treatment releases bound niacin).
• Low tryptophan intake (maize is tryptophan-poor).
• Historical: US South (1900s), institutional diets, famine.

Secondary (Impaired Utilization)

• Alcoholism (impaired tryptophan→niacin conversion, malnutrition).
• Malabsorption: Crohn's, celiac, carcinoid syndrome (tryptophan → serotonin).
• Drugs: Isoniazid (INH), 5-FU, 6-mercaptopurine, pyrazinamide, azathioprine.
• Hartnup disease (tryptophan transport defect).
• Carcinoid syndrome (tryptophan diverted to serotonin).

Clinical Features

Dermatitis (Photosensitive)

• Symmetrical, sun-exposed areas (neck = Casal's necklace, forearms, face, dorsa hands).
• Erythema → vesiculation → hyperpigmentation → scaling.
• Sharp demarcation at clothing lines.

Diarrhea

• Watery, sometimes bloody; glossitis, stomatitis, angular cheilitis.
• GI mucosal atrophy → malabsorption → worsening deficiency.

Dementia (Encephalopathy)

• Confusion, disorientation, memory loss, hallucinations, psychosis.
• Cerebellar signs: ataxia, tremor.
• Peripheral neuropathy (sensorimotor).
• Reversible if treated early.

Other

• Fatigue, weakness, anorexia, nausea.
• Pregnancy: fetal loss, congenital malformations.

Diagnosis

• Clinical (classic triad in risk context).
• Urinary N¹-methylnicotinamide (NMN) / 2-pyridone: low excretion.
• Serum tryptophan low; NAD/NADP in erythrocytes low.
• Response to niacin trial (therapeutic diagnosis).

Treatment

• Nicotinamide (niacinamide): 300-500 mg/day PO divided doses (preferred — no flushing).
• Niacin (nicotinic acid): 100-200 mg 3x/day (causes flushing).
• Multivitamin + B-complex (cofactor deficiencies often coexist).
• High-protein diet (tryptophan source) + nixtamalized corn if staple.
• Treat underlying cause (alcohol, malabsorption, drug adjustment).

Prognosis

• Rapid response: diarrhea improves in days; dermatitis in weeks; dementia reversible if not prolonged.
• Untreated: fatal within 4-5 years.

Prevention

• Fortification: mandatory niacin in enriched flour/cornmeal (US since 1940s).
• Dietary diversity: meat, fish, poultry, eggs, dairy, legumes, nuts, seeds, fortified grains.
• Niacin equivalents: 1 mg niacin = 60 mg tryptophan.

Pellagra is a disease of poverty and dietary monotony. Rare in developed nations except in alcoholism, malabsorption, or drug-induced states.