A 32-year-old woman presents with progressive loss of skin pigmentation over her hands, feet, and around her mouth over the past 6 months. On examination, the lesions show **sharp demarcation from normal skin** (marked **B** in the diagram), and appear chalk-white. Under Wood's lamp, the lesions appear bright bluish-white with enhanced contrast. She has a history of Hashimoto thyroiditis diagnosed 2 years ago. Based on the characteristic sharp demarcation and Wood's lamp findings, what is the most likely pathogenic mechanism underlying this condition?

Explanation

## Why T-cell mediated autoimmune destruction of melanocytes is right The sharply demarcated, chalk-white depigmented macules with Wood's lamp enhancement (bright bluish-white appearance) are pathognomonic for vitiligo. The pathogenesis is T-cell mediated autoimmune response against melanocytes, a multifactorial process involving genetic predisposition and environmental triggers (stress, trauma, sunburn). The sharp demarcation (marked **B**) reflects the focal, well-defined loss of melanocytes at the border between affected and normal skin. The patient's history of Hashimoto thyroiditis further supports autoimmune pathogenesis, as vitiligo is associated with autoimmune polyendocrine conditions in ~20% of cases. [Robbins 10e Ch 25] ## Why each distractor is wrong - **Fungal infection causing melanin depletion in the stratum corneum**: Fungal infections (like tinea versicolor) cause hypopigmentation but lack sharp demarcation and do not show the characteristic bright bluish-white appearance on Wood's lamp. The clinical presentation and Wood's lamp findings are diagnostic of vitiligo, not fungal disease. - **Genetic mutation in tyrosinase gene leading to melanin synthesis defect**: While tyrosinase mutations occur in oculocutaneous albinism (diffuse hypopigmentation from birth), vitiligo is acquired and shows focal, sharply demarcated lesions with normal melanocyte function in unaffected skin. The sharp demarcation indicates selective melanocyte loss, not a systemic enzyme defect. - **Epidermal barrier dysfunction with transepidermal water loss**: This mechanism is relevant in conditions like atopic dermatitis or ichthyosis, not vitiligo. Vitiligo is characterized by selective melanocyte destruction, not barrier dysfunction, and does not present with the characteristic sharp demarcation and Wood's lamp enhancement seen here. **High-Yield:** Vitiligo = sharply demarcated chalk-white macules + Wood's lamp enhancement + T-cell autoimmunity against melanocytes; check for associated autoimmune conditions (thyroid, B12, Addison, T1DM, alopecia areata). [cite: Robbins 10e Ch 25]