Stadtspital Triemli, Central Laboratory, University Hospital of Zurich, Zurich, Switzerland.
Photochem Photobiol. 2009 Nov-Dec;85(6):1434-9. doi: 10.1111/j.1751-1097.2009.00595.x.
Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle(4)-D-Phe(7)-alpha-MSH), a synthetic analog of alpha-melanocyte stimulating hormone and agonist of the melanocortin-1-receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained-release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60-day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low-grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open-label study, confirmation by a large-scale trial is required.
红细胞生成性原卟啉症（EPP）是一种罕见的遗传性疾病，其特征是皮肤中积聚光敏剂原卟啉 IX。在暴露于阳光后，由此产生的光敏性首先表现为疼痛，随后表现为红斑、水肿和皮肤损伤。阿法美拉诺肽（Nle（4）-D-Phe（7）-α-MSH）是α-促黑素细胞激素的合成类似物，也是黑素细胞刺激素-1 受体的激动剂，可促进黑色素合成，增加皮肤色素沉着。本研究探讨了阿法美拉诺肽预防 EPP 患者症状的疗效。给五名 EPP 患者皮下植入 20mg 缓释型阿法美拉诺肽，间隔 60 天植入两次。通过使用标准化的白光照射进行光激发试验、黑色素密度（MD）测定以及对阳光暴露和症状的日常记录来评估治疗效果。与基线相比，从第 30 天到第 120 天，对光激发的耐受性显著增加（P = 0.007），并且皮肤 MD 显著高于基线时的记录值（P = 0.004）。除了两次低度疼痛发作外，患者在治疗第 4 天之后再未记录到光毒性事件。对自然光的耐受性比治疗前延长了 24 倍。这些发现表明阿法美拉诺肽对 EPP 患者有有益的疗效。由于纳入的患者数量有限且设计为开放性研究，因此需要进行大规模试验来确认。
