A 52-year-old male laborer from rural Uttar Pradesh presents with a 4-month history of progressive dermatitis on his face, neck, and hands (areas exposed to sunlight), chronic diarrhea, and increasing irritability and poor memory. His diet consists mainly of corn and legumes with minimal vegetables, eggs, or meat. On examination, he has a sharply demarcated, hyperpigmented, scaly dermatitis in a 'glove and stocking' distribution on sun-exposed areas. His mental status is mildly impaired. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Pellagra (Niacin/Vitamin B3 Deficiency) ### The 4 Ds of Pellagra **Mnemonic: 4 Ds of Pellagra** = **D**ermatitis, **D**iarrhea, **D**ementia, **D**eath (if untreated) **Key Point:** Pellagra is a classic triad of: 1. **Dermatitis** — photosensitive, symmetrical, sharply demarcated, hyperpigmented, scaly rash on sun-exposed areas (face, neck, hands, feet) 2. **Diarrhea** — chronic, often bloody 3. **Dementia** — irritability, poor memory, confusion, psychosis (in advanced cases) ### Pathophysiology Niacin (Vitamin B3) is essential for: - **NAD^+^ synthesis** — cofactor in oxidative metabolism and DNA repair - **Tryptophan metabolism** — niacin can be synthesized from tryptophan (60 mg tryptophan = 1 mg niacin equivalent) Deficiency impairs: - Cellular energy production - DNA repair - Serotonin synthesis (→ psychiatric symptoms) ### Epidemiology in India **High-Yield:** Pellagra occurs in populations with: - **Corn-based diet** (especially if corn is not nixtamalized — alkali-treated to release bound niacin) - Low protein intake (↓ tryptophan conversion) - Chronic alcoholism (impaired absorption and metabolism) - Chronic diarrhea (↓ absorption) - Tuberculosis or malignancy (↑ niacin consumption) Rural India, particularly in Uttar Pradesh and Maharashtra, has pockets of endemic pellagra. ### Characteristic Dermatitis **Clinical Pearl:** The dermatitis of pellagra has a distinctive **"glove and stocking" or "Casal necklace"** appearance: - Sharply demarcated from normal skin - Hyperpigmented and scaly - **Photosensitive** — worse on sun-exposed areas - Symmetric distribution - May blister and become infected ### Differential Diagnosis Table | Condition | Dermatitis Pattern | GI Symptoms | Neuropsychiatric | Key Distinguishing Feature | |-----------|-------------------|-------------|------------------|---------------------------| | **Pellagra (Niacin ↓)** | Photosensitive, sharply demarcated, sun-exposed | Diarrhea (often bloody) | Dementia, irritability, psychosis | **4 Ds triad** + corn diet | | **Acrodermatitis (Zinc ↓)** | Perioral, perianal, acral (hands/feet) | Diarrhea | Alopecia, immune dysfunction | **Perioral/perianal** distribution; responds to zinc | | **Vitamin A deficiency** | Follicular keratosis, Bitot spots | Diarrhea | Night blindness, xerophthalmia | **Ocular findings** (Bitot spots, corneal scarring) | | **Vitamin E deficiency** | Rare dermatitis | Steatorrhea | Ataxia, neuropathy, retinopathy | **Neurological** (ataxia) > dermatitis | ### Diagnostic Confirmation - **Plasma niacin level** < 0.6 mg/dL (diagnostic) - **Urinary N-methylnicotinamide** < 0.5 mg/day (functional marker) - **Clinical response to niacin** — rapid improvement in dermatitis and diarrhea within days ### Management **Key Point:** Pellagra is rapidly reversible with niacin supplementation. - **Niacin (Nicotinic acid):** 50–100 mg PO three times daily, OR **Nicotinamide:** 50–100 mg PO three times daily - **Duration:** 2–4 weeks for clinical improvement; 3–6 months for complete resolution - **Dietary counseling:** Include fortified cereals, legumes, eggs, meat, peanuts - **Treat underlying cause:** Alcohol cessation, TB treatment, etc. **Warning:** Nicotinic acid (but NOT nicotinamide) causes flushing and may worsen glucose control — use nicotinamide in diabetics. ### Why Corn Diet? **High-Yield:** Corn contains niacin in a **bound form** that is not bioavailable unless alkali-treated (nixtamalization). Populations relying on corn as staple without nixtamalization are at high risk. ### Progression if Untreated 1. **Early:** Dermatitis, diarrhea 2. **Progressive:** Memory loss, irritability, confusion 3. **Advanced:** Psychosis, dementia, death (from secondary infections or metabolic derangement)