A 27-year-old man comes to the office for evaluation of a rash on both knees. The patient first noticed the rash 2 months ago. He has no other medical conditions and takes no medications. The patient smokes a half pack of cigarettes daily. Vital signs are normal. His knee is shown in the image below:
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Removal of the scale results in small bleeding points. As part of the treatment regimen, a topical vitamin D analog is prescribed. This medication is most likely to improve this patient's condition via which of the following mechanisms?
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This patient has psoriasis, a common skin disorder characterized by activation of T helper cells and proliferation of keratinocytes. Epidermal hyperplasia (acanthosis) produces erythematous plaques, and hyperkeratosis and confluent parakeratosis of the stratum corneum produce the characteristic scaling. The epidermal cell layer superficial to the dermal papillae may be thinned and contain dilated blood vessels, which can lead to pinpoint bleeding when the scale is removed (Auspitz sign).
First-line treatment options for localized psoriasis include topical corticosteroids (eg, diflorasone) and vitamin D analogs (eg, calcipotriene, calcitriol). Vitamin D analogs activate the vitamin D receptor, a nuclear transcription factor, resulting in inhibition of T-cell and keratinocyte proliferation and stimulation of keratinocyte differentiation. Corticosteroids also have anti-inflammatory and antiproliferative properties; their mechanism of action is complementary to vitamin D analogs, and the 2 agents work well in combination.
(Choice A) Tyrosinase is the primary enzyme responsible for oxidation of tyrosine, which serves as the rate-limiting step in synthesis of melanin. Tyrosinase inhibitors (eg, hydroquinone) decrease synthesis of melanin and can be used in treatment of hyperpigmentation disorders (eg, melasma).
(Choice B) Acne vulgaris is promoted by proinflammatory fatty acid production by Cutibacterium (Propionibacterium) acnes. Benzoyl peroxide has bacteriostatic properties against C acnes and reduces production of these inflammatory fatty acids.
(Choice C) Cutaneous warts are the most common manifestation of human papillomavirus infection. Imiquimod is a topical immunomodulator that likely induces local cytokine (eg, interferon-alpha, interleukin-6) production against the virus.
(Choice D) Prostaglandin E2 (which is produced by cyclooxygenase-2) is involved in mediating the tumorigenic effects of ultraviolet light in the skin, promoting the formation of actinic keratosis (AK) and squamous cell carcinoma. Topical diclofenac, a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase, can be used to treat AK.
Educational objective:
First-line treatment options for localized psoriasis include high-potency topical corticosteroids and vitamin D analogs. Vitamin D analogs inhibit T-cell and keratinocyte proliferation and stimulate keratinocyte differentiation. Corticosteroids also have anti-inflammatory and antiproliferative properties; their mechanism of action is complementary to the vitamin D analogs.