'Atrophic telogen effluvium' from cytotoxic drugs and a randomized controlled trial to investigate the possible protective effect of pretreatment with a topical vitamin D3 analogue in humans
'Atrophic telogen effluvium' from cytotoxic drugs and a randomized controlled trial to investigate the possible protective effect of pretreatment with a topical vitamin D3 analogue in humans
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DOI：
10.1111/j.1365-2133.2005.06608.x
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发表时间：
2005-07-01
影响因子：
10.3
通讯作者：
Hutchinson, PE
中科院分区：
文献类型：
--
作者：
Bleiker, TO;Nicolaou, N;Hutchinson, PE
背景细胞毒性药物引起的脱发通常归因于脱发(生长期脱发)。脱发也被描述过，但一些作者否认对头发周期有任何影响。目的探讨细胞毒性脱发的过程以及局部应用钙泊三醇对脱发的保护作用。方法对即将接受环磷酰胺600 mg m(-2)、甲氨蝶呤40 mg m(-2)和5-氟尿嘧啶600 mg m(-2)化疗周期的乳腺癌患者随机分为两组，分别接受钙泊三醇头皮液50mgm(-1)或赋形剂治疗。从化疗前4天开始，每天涂抹两次，每个治疗周期持续14天。摘掉、拔掉和剪下的头发进行了取样。结果10例接受钙泊三醇治疗的患者和14例接受治疗的患者完成了3个周期的治疗，9例患者完成了6个周期的治疗。钙泊三醇对化疗后最小程度脱发的患者比例、脱发率、拔除的脱发和断裂的毛发数量、脱发和拔出的头发的形态、头发再生或头发密度没有明显影响。综合治疗组的结果，化疗对脱发的影响有很大的差异，从5名患者完全脱发到5名患者没有明显脱发。排除后者，化疗期间脱发(平均81%的脱发)多于骨折(12%)和生发(6%)(P=0.0002)。主要病理改变为近端毛干逐渐变细，治疗过程中脱发平均3%上升至48%(P=0.0005)，而正常脱发下降，基线平均98%脱发下降至55%(P=0.0005)。病理的锥形端毛有正常或小的鳞茎，有时甚至很小。结论本研究中发现的细胞毒性药物的主要作用是毛干近端变细和毛囊过早进入休止素，这与毛囊在生长期持续受影响的传统观点相冲突。由此产生的分泌物是逐渐变细的端毛和断裂的头发的混合物。由于进入端原是脱发过程中不可或缺的一部分，细胞毒性脱发可以被认为是传统的“端原脱发”的一种变体，因此我们提出了“萎缩性脱发”这个术语。外用钙泊三醇对脱发无明显保护作用。
Background Hair loss from cytotoxic drugs is classically ascribed to the loss of fractured hairs (anagen effluvium). Telogen hair loss has also been described but some authors have denied any effect on the hair cycle. There are conflicting reports on a protective effect of pretreatment with a vitamin D analogue on cytotoxic drug-induced hair loss in rodents.Objectives To investigate the process of cytotoxic hair loss and any protective effect on the hair of pretreatment with topical calcipotriol.Methods Breast cancer patients who were about to receive cycles of chemotherapy with cyclophosphamide 600 mg m(-2), methotrexate 40 mg m(-2) and 5-fluorouracil 600 mg m(-2) were recruited and randomized to receive calcipotriol scalp solution 50 mu g mL(-1) or vehicle. The solution was applied twice daily from 4 days prior to chemotherapy and continued for 14 days in each treatment cycle. Shed, plucked and cut hairs were sampled. Absolute shed rates, the proportion of major hair types, the presence of proximal hair shaft changes, regrowth (using the new anagen hair count) and hair density were assessed.Results Ten patients receiving calcipotriol and 14 receiving vehicle completed three treatment cycles and nine from both groups completed six cycles. There was no detectable effect of calcipotriol on the proportion of patients experiencing minimal hair loss from chemotherapy, shed rates, plucked telogen and fractured hair counts, the morphology of shed and plucked hair, hair regrowth or hair density. Combining results of the treatment groups, there was a large variation in the impact of chemotherapy on hair loss, from total loss in five patients to no obvious loss in five. Excluding the latter, during chemotherapy shed telogen hairs (mean 81% of shed hairs) predominated over fractured (12%) and anagen hairs (6%) (P = 0.0002). The major pathological change was proximal hair shaft tapering, baseline mean 3% of shed hairs rising to 48% (P = 0.0005) during treatment, and there was a consequent decrease in normal telogen hairs, baseline mean 98% of all telogen hairs falling to 55% (P = 0.0005) during treatment. The pathological tapered telogen hairs had normal or small, sometimes diminutive, bulbs. Fracturing of hairs with diminutive bulbs produced typical 'exclamation mark' hairs.Conclusions The cardinal effects of cytotoxic drugs found in this study were tapering of the proximal hair shaft and premature entry of the follicle into telogen, conflicting with the conventional view that affected hair follicles continue in anagen. There was a resulting effluvium of a mixture of tapering telogen hairs and fractured hairs. As entry into telogen is an integral part of the process, cytotoxic hair loss may be regarded as a variant of the conventional 'telogen effluvium' and we propose the term 'atrophic telogen effluvium'. There was no obvious protective effect on the hair loss of prior treatment with topical calcipotriol.