Pellagra

Pellagra is a very rare disease caused by a deficiency in vitamin B3 (also known as vitamin PP or niacin). It presents with characteristic dermatitis along with gastrointestinal symptoms and, in advanced stages, neurological manifestations. Severe cases can lead to death in the absence of vitamin supplementation.

Pathophysiology and Etiologies

Niacin is a vitamin involved in the synthesis and metabolism of carbohydrates, fatty acids, and proteins. Its intake can be:

• Direct: Niacin is present in many animal (liver, poultry, etc.), plant (grains, vegetables, etc.), and mushroom sources.
• Indirect: The human body can metabolize tryptophan (an essential amino acid found in animal products) into niacin (a process that requires vitamin B6).

Etiologies of Pellagra:

• Malnutrition (main cause in developing countries)
• Alcoholism (main cause in developed countries)
• Highly restrictive diets
• Bariatric surgery
• Carcinoid syndrome
• Iatrogenic (inhibition of the conversion of tryptophan into niacin through various mechanisms): long-term treatment with isoniazid, fluorouracil, pyrazinamide, 6-mercaptopurine, hydantoin, ethionamide, phenobarbital, azathioprine, chloramphenicol.
• Hartnup disease (an autosomal recessive disorder characterized by an inability to absorb tryptophan)
• Cirrhosis and long-term digestive disorders

Clinical Presentation

• Photosensitive Dermatitis: Dark red, symmetrical rash mainly on sun-exposed areas, resembling "sunburn" (can be mistaken for "simple tanning" in milder forms), which may progress to desquamation. The tongue and oral mucosa can also become dark red.
• Nonspecific Gastrointestinal Manifestations: Diarrhea, nausea, vomiting.
• Neuropsychological Manifestations at a Generally Advanced Stage: Insomnia, anxiety, bradypsychia, confusion, hallucinations, dementia. Opposition hypertonia and myoclonus may also occur.

Association with manifestations of other deficiency-related diseases is common.

Additional Examinations

The diagnosis is mainly clinical. When available, a urinary N-methylnicotinamide test can be performed to confirm the deficiency.

Other additional examinations are only useful for differential diagnosis in cases of uncertainty.

Management and Treatment

• For Pellagra: Niacin supplementation (50 to 500 mg/day orally) along with a diet rich in tryptophan (at least 100g/day of protein, e.g., milk, eggs, meat).
• Correction of Other Associated Deficiencies: Multivitamin supplementation as a general principle.

Bibliography

Bradley WG et al., Neurology in clinical practice, 5th ed., Butterworth-Heinemann, e-dition, 2007

EMC, Traité de neurologie, Elsevier, 2018

Guilland JC, Vitamines hydrosolubles (I). Thiamine, riboflavine, niacine, acide pantothénique, vitamine B6 et biotine, Encyclopédie Médico-chirurgicale, Endocrinologie-Nutrition[10-546-A-10], Elsevier, Paris, 2012

Pazirandeh S et al., Overview of water-soluble vitamins, UpToDate, 2022