A 52-year-old man from rural Bihar presents with a 4-month history of progressive dermatitis over sun-exposed areas (face, neck, hands), chronic diarrhea, and recent onset confusion and irritability. His wife reports he has become increasingly forgetful. On examination, he has a well-demarcated, erythematous, scaly rash in a symmetrical distribution over the dorsal surfaces of the hands and neck. Serum albumin is 2.8 g/dL. He reports a diet consisting mainly of corn and millet. What is the most likely diagnosis?

Explanation

## Clinical Presentation: The 4 Ds of Pellagra This patient exhibits the classic triad of pellagra manifestations: **Dermatitis:** - Photosensitive, symmetrical rash on sun-exposed areas (face, neck, dorsal hands) - Well-demarcated, erythematous, scaly appearance - Characteristic **"glove and stocking" or "necklace" distribution** **Diarrhea:** - Chronic GI symptoms (4-month history) - Due to niacin deficiency affecting intestinal mucosa **Dementia (Neuropsychiatric):** - Confusion, irritability, memory loss - Progressive cognitive decline - Reflects central nervous system involvement ## Why Niacin (Vitamin B3) Deficiency? **Key Point:** Pellagra is caused by severe niacin deficiency. Niacin is an essential cofactor for NAD^+^/NADP^+^-dependent enzymes involved in energy metabolism, DNA repair, and neurotransmitter synthesis. Deficiency leads to cellular dysfunction across multiple organ systems. **High-Yield:** The **4 Ds mnemonic** is the gold standard for pellagra diagnosis: 1. **Dermatitis** (photosensitive, symmetrical) 2. **Diarrhea** (mucosal damage) 3. **Dementia** (CNS degeneration) 4. **Death** (if untreated) **Mnemonic: CORN = Pellagra Risk** - **C**orn-based diet (niacin bound, bioavailable form low) - **O**utdoor sun exposure (triggers dermatitis) - **R**ural, impoverished populations - **N**iacin deficiency (endemic in corn-dependent regions) **Clinical Pearl:** In India, pellagra is endemic in regions where corn and millet are staple grains (Bihar, Madhya Pradesh, Rajasthan). The niacin in corn is bound and not bioavailable unless the corn is alkali-treated (nixtamalization, as done in Mexico). ## Biochemistry of Niacin Deficiency **Key Point:** Niacin deficiency impairs: - **NAD^+^ synthesis** → reduced ATP production → cellular energy crisis - **DNA repair** → genomic instability - **Neurotransmitter synthesis** → serotonin, GABA dysfunction - **Myelin maintenance** → demyelination ## Differential Diagnosis Table | Feature | Pellagra (B3) | Dermatitis Herpetiformis | SLE | Zinc Deficiency | |---------|---|---|---|---| | **Rash distribution** | Sun-exposed (photosensitive) | Extensor surfaces, buttocks | Malar (butterfly), photosensitive | Perioral, perianal, acral | | **Diarrhea** | Yes (mucosal) | No (GI involvement rare) | No | Yes (common) | | **Dementia/CNS** | Yes (progressive) | No | Yes (but lupus serology+) | No | | **Serology** | Normal | Tissue transglutaminase (tTG) IgA+ | ANA+, anti-dsDNA+ | Normal | | **Diet history** | Corn/millet staple | Gluten exposure | N/A | Parenteral nutrition, malabsorption | | **Albumin** | Low (malnutrition) | Normal or low | Normal or low | Low | | **Response to niacin** | Rapid (days) | No | No | No | **Clinical Pearl:** The **rapid clinical response to niacin supplementation** (improvement in dermatitis within 24–48 hours, resolution of diarrhea within days) is diagnostic and therapeutic. ## Management 1. **Niacin supplementation:** 50–500 mg/day (depending on severity) 2. **Dietary counseling:** Diversify diet, include protein-rich foods (tryptophan is a niacin precursor) 3. **Sun protection:** Avoid sun exposure during acute phase 4. **Treat comorbidities:** Address malnutrition (low albumin), correct other vitamin deficiencies