A 48-year-old man with a 20-year history of alcohol dependence presents to the dermatology clinic with a 3-week history of watery diarrhea, progressive apathy, and a striking symmetric, sharply demarcated hyperpigmented scaly dermatitis. On examination, he has a broad necklace-shaped rash across the anterior neck and upper chest, with matching lesions on the dorsa of the hands and forearms in a "gauntlet" distribution. The condition marked **B** in the diagram is suspected. Which of the following biochemical defects BEST explains the pathophysiology of this condition?
A. Deficiency of NAD and NADP coenzymes due to niacin deficiency, impairing oxidation-reduction reactions and DNA repair
B. Impaired zinc absorption leading to loss of metalloproteins essential for immune function
C. Defective porphyrin synthesis causing accumulation of photosensitizing intermediates
D. Impaired complement-mediated clearance of immune complexes in photo-exposed skin
Explanation
Why "Deficiency of NAD and NADP coenzymes due to niacin deficiency, impairing oxidation-reduction reactions and DNA repair" is right
The condition marked B is pellagra, caused by deficiency of niacin (vitamin B3) or its precursor tryptophan. Niacin is the precursor of NAD (nicotinamide adenine dinucleotide) and NADP, which are essential coenzymes in oxidation-reduction reactions, DNA repair (particularly PARP-mediated pathways), and energy metabolism. The classic presentation of the 4 Ds (dermatitis, diarrhea, dementia, and death if untreated) reflects the systemic impact of impaired NAD/NADP-dependent metabolism. The photo-distributed dermatitis (Casal's necklace) and gauntlet distribution on the hands result from photosensitivity and the cumulative metabolic stress in sun-exposed areas. (Bolognia Dermatology 5e; Harrison's Principles of Internal Medicine 21e)
Why each distractor is wrong
Impaired zinc absorption leading to loss of metalloproteins essential for immune function: This describes acrodermatitis enteropathica (marked A), which presents with perioral and perianal dermatitis, not the photo-distributed Casal's necklace pattern. Zinc deficiency does not cause the 4 Ds triad.
Defective porphyrin synthesis causing accumulation of photosensitizing intermediates: This describes porphyria cutanea tarda (marked C), which presents with blistering and fragility in photo-exposed areas but lacks the diarrhea, dementia, and characteristic symmetric hyperpigmented scaly dermatitis of pellagra.
Impaired complement-mediated clearance of immune complexes in photo-exposed skin: This describes subacute cutaneous lupus erythematosus (marked D), which presents with annular or papulosquamous lesions in photo-exposed areas but is an autoimmune condition without the gastrointestinal and neuropsychiatric manifestations of pellagra.
High-YieldNEET PG
Pellagra = 4 Ds (dermatitis, diarrhea, dementia, death) + Casal's necklace + NAD/NADP deficiency; treat with nicotinamide 100–300 mg/day and address the underlying cause (alcohol cessation, dietary diversification, or treatment of Hartnup disease/carcinoid syndrome).
Bolognia Dermatology 5e; Harrison's Principles of Internal Medicine 21e
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