Hypercalcaemia and hypercalciuria after topical treatment of psoriasis with excessive amounts of calcipotriol.
Hypercalcaemia and hypercalciuria after topical treatment of psoriasis with excessive amounts of calcipotriol.
复制标题
用过量卡泊三醇局部治疗牛皮癣后出现高钙血症和高钙尿症。
DOI：
10.1080/000155599750011822
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发表时间：
1999
影响因子：
3.6
通讯作者：
D. Tsambaos
中科院分区：
文献类型：
--
作者：
S. Georgiou;D. Tsambaos
先生，维生素 D 类似物卡泊三醇局部治疗慢性斑块型银屑病的功效已在大量临床试验中得到证实 (1, 2)。尽管卡泊三醇对体内钙稳态的影响比 1,25-二羟基维生素 D3 低 100 倍，但如果使用过量，可能会导致高钙血症 (2, 3)。我们报道了一名患有全身性慢性斑块型银屑病的患者，局部应用过量的卡泊三醇（Dovonex1）软膏使他的病情得到显着改善，但也导致高钙血症和高钙尿症的发生。一名 73 岁男性，长期患有慢性斑块型银屑病，最近病情恶化，地蒽酚和阿维A治疗无效。红鳞状斑块覆盖了他体表约30%的面积。在彻底解释卡泊三醇可能产生的不良反应后，特别是在未经许可的情况下过量使用后，他被开了卡泊三醇软膏（50毫克/克），并被指示根据制造商的指导每天局部涂抹两次。治疗前血清调整钙水平在正常范围内（2.47 mmol/l；正常范围2.25^2.75 mmol/l）。 15天后，患者再次到我们门诊就诊，发现他每周使用卡泊三醇约420克，已持续两周。他的皮肤损伤有了显着的改善；体检其他方面均正常。血清调整钙水平升高（3.22 mmol/l），高钙尿症（11.05 mmol/24 h；正常范围 2.5 ^ 7.5 mmol/l）很明显。血清磷酸盐、镁、碱性和酸性磷酸酶、肝肾功能检查均未见异常。通过免疫放射分析（CIS，Sur，Yvette，法国）测量的血清完整甲状旁腺激素水平在正常范围内（23 pg/ml；正常值10^65 pg/ml）。停止卡泊三醇治疗，1周后血清调整钙水平和24小时尿钙排泄值均恢复正常。据报道，使用过量卡泊三醇的广泛性银屑病患者或每周使用约 100 g 药物的不稳定或脓疱性银屑病患者出现高钙血症，而且在两例斑块型银屑病患者中使用符合其许可规格的卡泊三醇时也出现高钙血症 (2, 3)。此外，在银屑病患者中每周局部使用 150 g 卡泊三醇 10 个月，或每周 200 ^ 300 g 和 360 g 持续两周后，观察到高钙尿症 (3)。有趣的是，在以最大推荐剂量 100 克/周使用该药物的患者中，尿钙排泄量也有所增加 (3)。这些报告与我们的观察相结合表明，即使是短期局部应用卡泊三醇也能够影响全身钙稳态。目前认为卡泊三醇的这种作用是通过增强肠道对钙和磷酸盐的吸收来介导的，这可能导致高钙血症和/或高钙尿症、高磷酸盐血症和高磷酸尿症，并抑制甲状旁腺激素和 1,25 二羟基维生素 D3 (3)。在我们的病例中，血清磷酸盐和甲状旁腺激素水平被发现在正常范围内。然而，由于没有这些参数的基线值，因此仍不清楚治疗是否对它们产生任何调节作用。尽管迄今为止所有报道的病例在停止治疗后血清和尿钙水平均恢复正常，但卡泊三醇引起的高钙血症和高钙尿症是值得严重关注的不良反应。因此，密切监测银屑病患者的血清钙水平和尿液排泄率至关重要，特别是在长期卡泊三醇治疗下，即使遵守制造商的指南也是如此。
Sir, The e¤cacy of the vitamin D analogue calcipotriol in the topical treatment of chronic plaque psoriasis has been established in a large number of clinical trials (1, 2). Although calcipotriol has 100 times less e¡ect on calcium homeostasis in vivo than 1,25-dihydroxyvitamin D3, it may cause hypercalcaemia if used to excess (2, 3). We report a patient su¡ering from generalized chronic plaque psoriasis, in whom topical application of excessive amounts of calcipotriol (Dovonex1) ointment resulted in an impressive improvement of his condition, but also in the development of hypercalcaemia and hypercalciuria. A 73-year-old man with a long history of chronic plaque psoriasis presented with a recent exacerbation of his disorder refractory to therapy with dithranol and acitretin. The erythematosquamous plaques covered about 30% of his body surface. Subsequent to a thorough explanation of the possible adverse e¡ects of calcipotriol, particularly after its excessive unlicensed usage, he was prescribed calcipotriol ointment (50 mg/g) and was instructed to apply it topically twice daily according to the manufacturer's guidelines. Pretreatment serum adjusted calcium levels were within normal limits (2.47 mmol/l; normal range 2.25 ^ 2.75 mmol/l). Fifteen days later the patient was seen again in our outpatient department and it was found that he had been applying approximately 420 g of calcipotriol per week for 2 weeks. His skin lesions revealed an impressive improvement; the physical examination was otherwise normal. Serum-adjusted calcium levels were elevated (3.22 mmol/l) and hypercalciuria (11.05 mmol/24 h; normal range 2.5 ^ 7.5 mmol/l) was evident. Serum phosphate, magnesium, alkaline and acid phosphatase, liver and renal function tests showed no abnormalities. Serum intact parathyroid hormone levels measured by immunoradiometric assay (CIS, Sur, Yvette, France) were within normal limits (23 pg/ml; normal values 10 ^ 65 pg/ml). Calcipotriol therapy was discontinued and 1 week later the values of both serum-adjusted calcium levels and 24-h urine calcium excretion returned to normal. There have been reports of hypercalcaemia in patients either with extensive psoriasis who used excessive amounts of calcipotriol or with unstable or pustular psoriasis who had applied approximately 100 g of the drug per week, but also in two cases with plaque psoriasis using calcipotriol within its licensed speci¢cation (2, 3). Additionally, hypercalciuria has been observed in psoriatic patients subsequent to topical use of 150 g calcipotriol per week for 10 months, or of 200 ^ 300 g and 360 g per week for two weeks (3). Interestingly, a rise in urine calcium excretion has also been demonstrated in patients using the drug at the maximum recommended rate of 100 g/week (3). These reports taken together with our observation indicate that even short-term topical application of calcipotriol is capable of a¡ecting systemic calcium homeostasis. This e¡ect of calcipotriol is presently thought to be mediated by an enhancement of intestinal absorption of calcium and probably of phosphate, which may result in hypercalcaemia and/or hypercalciuria, hyperphosphataemia and hyperphosphaturia and in suppression of parathyroid hormone and 1,25 dihydroxyvitamin D3 (3). In our case serum phosphate and parathyroid hormone levels were found to be within normal limits. However, since no baseline values of these parameters were available, it remains unknown whether therapy had exerted any modulatory e¡ect on them. Although in all reported cases so far serum and urine calcium levels returned to normal after discontinuation of therapy, calcipotriol-induced hypercalcaemia and hypercalciuria are adverse e¡ects of serious concern. It is, therefore, of essential importance to closely monitor the serum levels and the urine excretion rate of calcium in psoriatic patients, particularly under long-term calcipotriol therapy, even when the manufacturer's guidelines are adhered.