Pellagra is a systemic nutritional disorder caused by deficiency of niacin (vitamin B3) or its precursor tryptophan. Niacin is essential for synthesis of the coenzymes:

• NAD (Nicotinamide adenine dinucleotide)

• NADP (Nicotinamide adenine dinucleotide phosphate)

These coenzymes are required in over 400 cellular oxidation-reduction reactions, making tissues with high metabolic turnover (skin, brain, gastrointestinal tract) most vulnerable.

The disease classically presents with the 3 D’s:

• Diarrhoea

• Dermatitis

• Dementia

Untreated cases progress to the 4th D — Death.

Pellagra rarely occurs in isolation and is commonly associated with multiple micronutrient deficiencies, especially in malnutrition and chronic alcoholism.

2. Physiology and Pathophysiology

Biological Functions of Niacin

Pathogenesis

Niacin deficiency causes cellular energy failure → tissue degeneration.

Affected organs and mechanisms

Tryptophan Link

60 mg tryptophan ≈ 1 mg niacin

Conditions reducing tryptophan availability cause pellagra:

• Protein deficiency

• Carcinoid syndrome (tryptophan diverted to serotonin)

• Hartnup disease (amino acid transport defect)

3. Risk Factors

Nutritional Causes

• Severe malnutrition

• Maize-based diets (untreated maize lacks bioavailable niacin)

• Refugee or famine settings

• Elderly with poor intake

Disease-Associated

• Chronic alcoholism (most common cause worldwide)

• Chronic diarrhea

• HIV infection

• Liver cirrhosis

• Malabsorption syndromes

• Post-bariatric surgery

• Anorexia nervosa

Drug-Induced

• Isoniazid

• 5-fluorouracil

• Azathioprine

• Chloramphenicol

Genetic/Metabolic

• Hartnup disease

• Carcinoid syndrome

4. Clinical Features

Classical Triad

A. Dermatitis

Photosensitive and symmetrical rash on sun-exposed areas:

• Face (Casal necklace around neck)

• Hands and forearms

• Feet

Progression:Erythema → hyperpigmentation → scaling → thickened skin

B. Gastrointestinal

• Diarrhoea (watery or bloody)

• Glossitis

• Stomatitis

• Abdominal pain

• Weight loss

• Malabsorption

C. Neurological (Dementia)

Early:

• Irritability

• Poor concentration

• Insomnia

• Anxiety

Late:

• Confusion

• Hallucinations

• Psychosis

• Memory loss

• Encephalopathy

Other Features

• Apathy

• Depression

• Peripheral neuropathy (late)

• Anemia (associated deficiencies)

5. Diagnostic Criteria

Diagnosis is mainly clinical, especially in low-resource settings.

Suspect pellagra when:

1. Photosensitive dermatitis AND

2. Chronic diarrhea OR neuropsychiatric symptoms AND

3. Risk factor (malnutrition/alcoholism)

Rapid response to niacin therapy confirms diagnosis

6. Investigations

Laboratory Tests

Differential Diagnoses

• Systemic lupus erythematosus

• Photosensitive drug eruption

• Porphyria cutanea tarda

• Vitamin B6 deficiency

• Zinc deficiency

7. Management

A. Non-Pharmacological

Lifestyle

• Stop alcohol use

• Treat underlying disease

• Sun protection

• Correct overall malnutrition

Dietary Advice

Increase intake of niacin-rich foods:

• Liver, kidneys, meats, poultry, fish

• Peanuts

• Milk

• Pulses

• Whole meal wheat and bran

Also increase protein intake to supply tryptophan.

B. Pharmacological Treatment

Severe Deficiency

Children

• Nicotinamide 50 mg PO every 8 hours × 1 week

Adults

• Nicotinamide 100 mg PO every 8 hours × 1 week

Mild Deficiency

Children

• Nicotinamide 50 mg PO daily × 1 week

Adults

• Nicotinamide 100 mg PO daily × 1 week

Supportive Therapy

• Oral rehydration for diarrhea

• Multivitamin supplementation

• High-protein diet

Why Nicotinamide (Not Nicotinic Acid)?

Nicotinamide is preferred because it:

• Does not cause flushing

• Has equal therapeutic effect

• Better tolerated

8. Monitoring and Follow-Up

Lack of improvement → reconsider diagnosis.

9. Complications if Untreated

• Severe dehydration

• Persistent encephalopathy

• Secondary infections

• Multi-organ failure

• Death

10. Prevention

High-Risk Groups

• Alcohol dependence

• Malnutrition

• Refugee populations

• HIV infection

• Chronic illness

Preventive Measures

• Balanced protein diet

• Food fortification

• Multivitamin supplementation

Recommended dietary allowance (RDA):

• Adult men: 16 mg/day

• Adult women: 14 mg/day

11. Prognosis

• Rapid recovery if treated early

• Skin changes reversible

• Late neurological damage may persist