6只犬毛发周期停滞(X脱毛)中毛发再生的最佳微针长度 ...

王帆

Optimal microneedle len

gth for hair regrowth in hair cycle arrest (alopecia X) in six dogs

6只犬毛发周期停滞(X脱毛)中毛发再生的最佳微针长度

 

作者：Yeong-Hun Kang1 | Min-Sun Kim1 | Soh-Yoon Kang1 | Jae-Eun Hyun| Cheol-Yong Hwang

 

翻译：王帆

 

Abstract

Background: Hair cycle arrest (HCA) is a chronic alopecic disorder in dogs. Clinical responses vary and are often insufficient. Microneedling (MN) has been used as a successful treatment for HCA in dogs; ideal protocols have not yet been established.

Objectives: The objective of the study was to compare the efficacy and safety of three needle lengths for MN in dogs with HCA.

Animals: Six unrelated client-owned dogs, including five Pomeranians and one mixed-breed dog, diagnosed with HCA.

Materials and Methods: Individual alopecic sites were divided into three sections. For each section, different lengths of needles (1, 2 and 3mm) were used. Efficacy and safety were evaluated at 1, 3 and 6 months. Treated sections were monitored for 20 months.

Results: Three months after treatment with 3mm needles, all sections showed hair regrowth. There was no hair regrowth in two of six sections treated with 2mm needles, and four of six sections did not show a response to treatment with 1mm needles. Two dogs developed transient pruritus. Five of six dogs had recurrent hair loss between 5 and 16 months of follow-up.

Conclusion and Clinical Relevance: Microneedling using longer needles stimulated better hair regrowth in dogs with HCA. Alopecia relapsed in most dogs and minor pruritus occurred in some dogs.

摘要:

背景:毛发周期停滞(HCA)是犬的一种慢性脱毛症。临床效果各不相同，而且往往治疗效果差。微针(MN)已被用于成功治疗犬HCA；理想的疗程尚未建立。

目的:比较三种长度微针治疗犬HCA的疗效和安全性。

动物:六只非家养犬，包括五只博美犬和一只混血犬，被诊断为HCA。

材料和方法:将一处脱毛部位分为三个区域。对于每个区域，使用不同长度的针(1、2和3mm)。在第1、3和6个月评估疗效和安全性。对经治疗区域进行20个月的监测。

结果:3mm针治疗3个月后，所有区域均显示毛发再生。在用2mm针治疗的六个区域中的两个区域中没有毛发再生，并且用1mm针治疗的六个区域中，四个区域没有效果。两只犬出现短暂性瘙痒。六只犬中有五只在随访的5到16个月内脱毛复发。

结论和临床相关性:使用较长针头的微针刺激HCA犬，可见更好的毛发再生。大多数犬的脱毛会复发，一些犬出现轻微瘙痒。

 

 

INTRODUCTION

介绍

Hair cycle arrest (HCA) is characterised by noninflammatory symmetrical alopecia on the trunk; it typically spares the extremities and head. Hair cycle arrest is common in Pomeranian dogs. The condition is considered a cosmetic problem; endocrinopathies, such as hypothyroidism and hyperadrenocorticism, may present with similar dermatological signs and should be ruled out to confirm HCA. The pathogenesis of HCA is unclear. There is evidence for a genetic origin, such as the early age of onset and breed predisposition. Differentially regulated genes and the genetic features of HCA have been explored using transcriptome profiling and whole-genome sequencing.

毛发周期停滞(HCA)的特征是躯干非炎性对称性脱毛;它通常不累及到四肢和头部。毛发周期停滞在博美犬中很常见。这种情况被认为是美观性问题;内分泌疾病，如甲状腺功能减退和肾上腺皮质功能亢进，可出现类似的皮肤症状，应进行排除以确诊HCA。HCA的发病机制尚不明确。有证据表明有遗传起源，例如发病年龄较早和有繁殖倾向。通过转录组分析和全基因组测序，已经探索了HCA的差异调节基因和遗传特征。

 

Although HCA is considered a cosmetic disease, some owners and breeders are desperate to treat the hair loss. Various treatments have been tried, including growth hormone, castration, o,p’-DDD (mitotane), melatonin, trilostane, medroxyprogesterone acetate and deslorelin. Success rates reported with these treatments vary, with 50%–100% of dogs showing partial to complete hair regrowth. None of the aforementioned therapies guarantee success in all dogs. Low-level laser therapy and microneedling have shown promising results. More research is needed to determine standard protocols and assess efficacy and safety. There is no gold standard treatment for this disorder.

虽然HCA被认为是一种美观性疾病，但一些主人和饲养者不顾一切地治疗脱毛。人们尝试了各种治疗，包括生长激素、去势手术、o、p’-DDD(米托坦)、褪黑素、曲洛斯坦、醋酸甲羟孕酮和地洛瑞林。这些治疗的成功率各不相同，50%-100%的犬显示毛发部分或完全再生。上述所有的治疗方法都不能保证对所有的犬都有效。低能量激光疗法和微针疗法已经显示出有前景的结果。需要开展更多研究来确定标准方案并评估疗效和安全性。这种疾病没有金标准治疗方法。

 

Pomeranian dogs with HCA showed downregulation of Wnt/beta-catenin pathway-related genes and the MAP3K mutation, which is related to the noncanonical Wnt pathway. In the anagen phase, stem cells in the dermal papilla send proliferative signals to stimulate the formation of new hair, and this communication is mediated by the Wnt/beta-catenin pathway. Microneedling is a procedure that creates micro-wounds in the skin, stimulating the wound-healing process, which induces the regeneration of hair follicles. The proteins Wnt3A and Wnt10B in hair follicles had elevated expression after MN. Additionally, MN induces revascularisation of the skin, which provides proper nourishment for hair growth. Some reports show that in dogs with HCA, MN results in remarkable and permanent hair regrowth with negligible adverse effects.

博美犬HCA表现为Wnt/β-连环蛋白通路相关基因下调和MAP3K突变，与非经典Wnt通路相关。生长期，真皮乳头中的干细胞发出增殖信号以刺激新毛发的形成，这种通信是由Wnt/β-连环蛋白通路介导的。微针是一种在皮肤上制造微伤口的方法，刺激伤口愈合过程，从而诱导毛囊再生。MN后毛囊中Wnt3A和Wnt10B蛋白表达升高。此外，MN诱导皮肤血管重建，为毛发生长提供适当的营养。一些报告表明，在患有HCA的犬中，MN导致显著和永久的毛发再生，并且可以忽略不良影响。

 

In mice, 0.25 and 0.5mm needles produced significantly more hair growth than other needle lengths. In dogs, the reported lengths of needles were 1.5 and 2.5mm. The needle length should be optimised to minimise pain, reduce the use of analgesic drugs and increase hair regrowth. This study was designed to identify the ideal needle length for MN for treating HCA in dogs.

在小鼠中，与其他长度的针头相比，0.25和0.5mm针头的毛发生长明显更多。在犬中，报告的针长度为1.5和2.5毫米。针的长度应优化，以尽量减少疼痛，减少使用止痛药物，并促进毛发再生。本研究旨在确定MN治疗犬HCA的理想针长。

 

MATERIALS AND METHODS

材料和方法

Ethics

伦理

The procedures performed in this study were approved by the Institutional Animal Care and Use Committee of Seoul National University (SNU-IACUC, permit no. SNU-201221-1-1). The owners were informed of the entire experimental process and signed consent forms prior to participation.

本研究采用的方法经首尔国立大学动物保护与使用委员会(SNU-IACUC)批准，许可号:snu - 201221 - 1 - 1)。业主被告知整个实验过程，并在参与前签署了同意书。

 

Inclusion criteria

入选标准

1. Dogs with symmetrical noninflammatory truncal alopecia, excluding the head and legs, with hair loss of >75%.

2. Age at onset of ＜2 years.

3. Trichogram showing telogenisation of hair follicles and histopathological findings consistent with HCA.

4. Dogs without evidence of fungal or parasitic infection found during dermatological examination (trichogram, Wood's lamp examination, skin scraping and fungal culture).

1.犬表现对称性非炎性躯干性脱毛，不包括头部和腿部，脱毛>75%。

2.发病年龄<2岁。

3.毛发检查显示静止期毛囊，组织病理学结果与HCA一致。

4.犬在皮肤检查(毛发检查、伍氏灯检查、皮肤刮片和真菌培养)中未发现真菌或寄生虫感染证据。

 

Exclusion criteria

排除标准

1. Dogs receiving oral corticosteroid therapy at the time of presentation or within the previous two months.

2. Dogs with skin diseases or other underlying diseases associated with nonpruritic hair loss (e.g. hyperadrenocorticism and hypothyroidism).

3. Dogs receiving treatment with melatonin, trilostane, deslorelin, growth hormone, mitotane (o, p’-DDD) or medroxyprogesterone acetate for alopecia within the past three months.

4. Dogs neutered within the past three months.

1.在发病时或发病前两个月内接受口服皮质类固醇治疗的犬。

2.患有皮肤病或其他与非瘙痒性脱毛相关的潜在疾病(如肾上腺皮质亢进和甲状腺功能减退)的犬。

3.在过去三个月内接受褪黑素、曲洛斯坦、地洛瑞林、生长激素、米托坦(o, p ' -DDD)或醋酸甲孕酮治疗脱毛的犬。

4.在过去三个月内进行节育的犬。

 

Animals

动物

Unrelated client-owned dogs diagnosed with HCA in the Department of Dermatology, Seoul National University, Veterinary Medical Teaching Hospital (SNUVMTH) were enrolled in this study based on the inclusion criteria. Dermatological examinations, including trichogram, cytological evaluation and fungal culture, were performed to rule out other dermatological disorders. Physical examination and blood analysis (i.e. serum chemistry analysis, complete blood count, thyroid-stimulating hormone, free thyroxine and total thyroxine quantification) were performed to rule out other conditions.

根据纳入标准，选取首尔大学兽医教学医院皮肤科诊断为HCA的无亲缘关系的家养犬。同时进行皮肤检查，包括毛发检查、细胞学检查和真菌培养，以排除其他皮肤病。进行体格检查和血液分析(即血清化学分析、全血细胞计数、促甲状腺激素、游离甲状腺素和总甲状腺素定量)以排除其他疾病。

 

Skin biopsies were performed 10 min after local injection with 1mL of lidocaine (20mg per site, Lidocaine HCl Hydrate injection 2%; Daihan Pharm Co. Ltd). For each dog, two skin biopsies were obtained from alopecic skin using 6mm punches and were fixed in 10% buffered formalin. The samples were embedded in paraffin, cut into 4μm sections and stained with haematoxylin and eosin following standard procedures.

局部注射利多卡因1mL (20mg/部位，2%盐酸利多卡因注射液)。对每只犬，用6毫米的打孔器从脱毛皮肤上采集两个皮肤活检，并将其固定在10%的缓冲福尔马林中。样本包埋在石蜡中，切成4μm的切片，并按照标准程序进行苏木精和伊红染色。

 

Microneedling

微针

Alopecic lesions of the dorsum were divided into three 4×4cm sections. Each section was assigned to one needle length of 1, 2 or 3mm using a blue marker (Figure 1a). Before MN, the selected body sites were disinfected with 2% chlorhexidine. Lidocaine 2.5% and prilocaine 2.5% cream (0.1g/cm2 , EMLA, Mitsubishi Tanabe) were applied before the procedure, under an impermeable occlusion dressing (Tegaderm, 3M Corporation) for 1h. All dogs were sedated by intramuscular injection of medetomidine (0.02mg/kg, Domitor; Zoetis). Intravenous injection of alfaxalone (0.2mg/kg, Alfaxan; Jurox Pty Ltd) was added when dogs moved during the procedure.

将背部脱毛病变分为3个4×4cm区段。使用蓝色标记将每个切片分配为1、2或3mm的针长(图1a)。MN前用2%氯己定对选定部位进行消毒。术前使用2.5%利多卡因和2.5%丙氨卡因乳膏(0.1g/cm2)，在不透水的封闭3M敷料敷1h。所有犬均肌内注射美托咪定(0.02mg/kg)。术中患犬有反应时同时静脉注射阿法沙酮(0.2mg/kg)。

 

All MN procedures were performed by the same veterinarian. Sterile MN devices (Dermaroller; ZGTS) with three needle lengths were applied aseptically to each section (1, 2 and 3mm) vertically, horizontally and obliquely. The procedure was performed for each section until mild capillary bleeding was observed.

所有MN手术均由同一名兽医进行。每个区域分别用1、2、3mm针长的无菌MN装置垂直、水平和斜向使用。每个区域都要进行手术，直到观察到轻度毛细血管出血。

 

Evaluation

评估

All dogs were examined four times: first for MN treatment, and then 1, 3 and 6 months after treatment. Hair regrowth and adverse reactions were assessed by the clinician who performed MN. Subjective hair regrowth was evaluated using a 5-point Likert scale, as follows: 0=no improvement; 1=1%–25% improvement; 2=26%–50% improvement; 3=51%–75% improvement; 4=76%–100% improvement). Haemorrhage, erythema and oedema were recorded with ×50 magnified photographs (Folliscope 5.0; Anagen Corp.) and global photographs immediately after MN for each site. The presence of pruritus, pain, depressed attitude and recurrence of hair loss after the procedure were obtained from the owner by email and phone consults. The dogs were monitored for recurrence of alopecia and adverse reactions for 20months after treatment.

所有犬分别于治疗前、治疗后1、3、6个月进行4次检查。毛发再生和不良反应由进行MN的临床医师进行评估。采用5分Likert量表对毛发再生情况进行主观评价，如下:0=无改善;1 = 1%改善-25%;2 = 26%-50%改善;3 = 51%-75%改善;4 = 76%-100%改善)。使用×50放大照片，并在MN之后立即为每个点拍摄全景照片。通过邮件和电话询问患犬术后有无瘙痒、疼痛、精神沉郁及脱毛复发情况。治疗后随访20个月，观察脱毛复发及不良反应。

 

RESULTS

结果

Of the six dogs that met the inclusion criteria, five were Pomeranians and one was a wire-haired, 20kg mixed-breed dog. All were neutered (two castrated males, four spayed females) and were younger than two years of age at the onset of alopecia. Five of the six dogs had received prior treatment for HCA and had not responded (Table 1).

在符合入选标准的6只犬中，有5只是博美犬，1只是20公斤重的刚毛混血犬。所有已节育(两只已去势雄性，四只已绝育雌性)，在脱毛发病时年龄小于两岁。6只犬中有5只先前接受过HCA治疗，但没有效果(表1)。

 

Skin biopsies were taken from five of six dogs; the owner of one dog (Case 5) declined biopsy collection. Histopathological examinations revealed telogen-dominant follicles, excessive trichilemmal keratin and atrophic sebaceous glands.

对6只犬中的5只进行了皮肤活检;其中一只犬(病例5)的主人拒绝活检。组织病理学检查显示静止期毛囊为主，毛膜角蛋白过多，皮脂腺萎缩。

 

Hair regrowth is shown in Figure 2 and Table S1. All sections in all dogs treated with 3mm needles showed hair regrowth by three months, and the quality of hair growth increased by six months (Figures 1c and 3b). By contrast, the 1mm needles produced hair growth in only two dogs. Hair growth was noted adjacent to the 3-mm-treated sections in two dogs (cases 1 and 6). Longer needles caused more haemorrhage, erythema and oedema compared to shorter needles (Figure 4c–f).

毛发再生见图2和表S1。用3mm针头治疗的所有犬的所有切片在3个月时显示毛发再生，并且毛发生长的质量在6个月时增加(图1c和3b)。相比之下，1毫米的针头只在两只犬上产生了毛发。在2只犬(病例1和6)的3毫米处理的切片旁可见毛发生长。较长的针头比较短的针头引起更多的出血、发红和水肿(图4c-f)。

 

The topical analgesic and medetomidine sedation protocol was sufficient for treatment with 1mm needles in all dogs. Alfaxalone was required in four dogs (Cases 1, 3, 4 and 5) for treatment with 2mm needles and all dogs needed alfaxalone for treatment with 3mm needles.

所有犬的局部镇痛和美托咪定镇静方案足以使用1mm针头进行治疗。4只犬(例1、3、4、5)用2mm针头需要注射阿法沙酮，所有犬用3mm针头需要注射阿法沙酮。

 

Pruritus was the primary reported adverse effect. The owner of Case 3 reported severe pruritus post-treatment. The dog had a history of mild pruritus yet had never been administered medications for pruritus before the procedure. The exacerbated pruritus, attributed to MN, was controlled with 0.5mg/kg prednisolone (Solondo Tab; YuHan Corp.) orally once daily for two weeks. Hair regrowth was noted two months later in the self-traumatised areas (Figure 4a,b). Owners of the Pomeranian dogs reported varying degrees of depressed attitude, lasting from minutes to hours after the MN procedure. There was no reported loss of appetite or vocalising.

瘙痒是报告的主要不良反应。例3患犬主诉治疗后出现严重瘙痒。这只犬有轻度瘙痒的病史，但在手术前从未接受过治疗瘙痒的药物治疗。由MN引起的瘙痒加重用0.5mg/kg泼尼松龙控制，每日一次，连续两周。2个月后在自我创伤的区域观察到毛发再生(图4a,b)。博美犬的主人报告说，在MN手术后，他们有不同程度的精神沉郁，持续时间从几分钟到几小时不等。没有食欲下降或吠叫报告。

 

Recurrence of hair loss began as soon as five months in the mixed-breed dog, and between 14 and 16 months in the Pomeranian dogs (Figures 1d and 3d). One dog had no recurrence of hair loss and was monitored for 12months.

混血犬最早在5个月时就开始复发脱毛，博美犬在14至16个月之间开始复发脱毛(图1d和3d)。其中一只犬没有复发脱毛，并监测了12个月。

 

DISCUSSION

讨论

Identifying the ideal needle size for MN in dogs is important to reduce pain, decrease the use of analgesic drugs, minimise adverse reactions and improve efficacy. Microneedling with 3mm needles induced more rapid and higher quality hair growth in dogs with HCA compared to 1 and 2mm needles. This is in contrast to previous reports describing prominent hair regrowth with both 1.5 and 2.5mm needles. Factors such as the skin thickness, severity of alopecia, clinician technique, devices used, and anatomical sites chosen may have influenced the outcomes.

确定适合犬MN的针型对于减轻疼痛、减少镇痛药物使用、减少不良反应、提高疗效具有重要意义。与1毫米和2毫米的微针相比，3毫米的微针诱导HCA犬毛发生长更快、质量更高。这与之前报道的1.5 mm和2.5mm针的毛发再生情况形成了对比。皮肤厚度、脱毛严重程度、临床医师技术、使用的器械和选择的解剖部位等因素可能影响结果。

 

One explanation for these contrasting results could be differences in skin thickness. The thickness of dog skin varies by individual, with a range of 0.5–5mm. The actual maximum depth of tissue penetration of MN has been examined in people. Microneedles with lengths of ≤1mm did penetrate the tissue to their full length, yet longer needles (1.5–2.5mm) did not penetrate the tissue to their full length. This gap may be a result of varying thickness of the epidermis and dermis on formalin-fixed tissue. We therefore suspect that the 1mm needles penetrated the superficial dermis only, which was insufficient to reach the dermal papilla in the deep dermis. Further studies are required to con - firm this theory in dogs.

对这些不同结果的一种解释可能是皮肤厚度的差异。犬皮厚度各不相同，0.5-5mm不等。已在人体中检测了MN组织穿透的实际最大深度。长度≤1mm的微针可以完全穿透组织，而更长的针(1.5-2.5mm)不能完全穿透组织。这种间隙可能是福尔马林固定组织上表皮和真皮厚度不同的结果。因此，我们怀疑1mm的针头仅穿过真皮浅层，不足以到达真皮深层的真皮乳头。需要进一步的研究来证实这一理论在犬。

 

One report revealed that certain body sites, such as the hind legs, rump and tail, were less responsive to MN in dogs, while another report did not. In this study, we assumed that certain body sites were less responsive to MN because the device could not be firmly applied to the uneven surface. Therefore, the dorsum was selected for our study.

一份报告显示，犬的某些身体部位，如后腿、臀部和尾巴，对MN的反应较弱，而另一份报告则没有。在本研究中，我们假设某些身体部位对MN的反应较弱，因为该装置不能牢固地应用于凹凸不平的表面。因此，我们选择背部作为研究区域。

 

Hair regrowth adjacent to the MN sites suggests the possibility that molecules facilitating hair regeneration might influence nearby follicles. This phenomenon was seen in two of the six dogs. Earlier studies on Pomeranian dogs with HCA indicated downregulation of certain genes in the Wnt pathway. MN is known to activate Wnt proteins from skin wounds, it is hypothesised that some of these proteins might influence surrounding tissues.

靠近MN位点的毛发再生表明促进毛发再生的分子可能会影响附近的毛囊。这一现象在6只犬中的2只身上发现。早期对患有HCA的博美犬的研究表明，Wnt通路中的某些基因下调。已知MN可激活皮肤伤口中的Wnt蛋白，假设其中一些蛋白可能影响周围组织。

 

Recurrence of alopecia was observed in five of the six dogs. The one dog without recurrent hair loss was observed for the shortest period of time, so it cannot be known if the hair regrowth was truly permanent. The finding of hair loss beginning at up to 20 months after MN treatment suggests that dogs in previous reports considered to have permanent hair regrowth might in fact have experienced recurrence of alopecia if observation times had been longer. Interestingly, the mixed-breed dog in this study lost hair faster than the Pomeranian dogs; we suspect this was the result of a shorter hair cycle.

6只犬中有5只出现脱毛复发。没有反复脱毛的那只犬的观察时间最短，所以不能知道毛发再生是否真正永久。在MN治疗后20个月开始脱毛的发现表明，在以前的报告中，如果观察时间更长，被认为有永久性毛发再生的犬实际上可能经历了脱毛的复发。有趣的是，在这项研究中，混合品种的犬比博美犬掉毛更快;我们怀疑这是毛发周期较短的结果。

 

The adverse effects of MN in humans are generally transient and minor, including erythema, pain, oedema, haemorrhage, pruritus, granulomatous reaction and regional lymph node enlargement. In dogs, temporary erythema with haemorrhage has been reported. In this study, two of the six dogs showed pruritus, which is a commonly reported adverse effect on the human scalp, yet has not been reported in dogs. Pruritus in one of the dogs (Case 4) lasted about for about two weeks, which was attributed to healing, and did not re - quire additional therapy. For another pruritic dog (Case 3), it was difficult to determine if it was caused by MN because the dog had existing mild pruritus before the procedure. However, immediately after the MN procedure, the dog developed severe excoriations. Despite this, the pruritus did not last long, worsen or lead to excoriations during >12months of monitoring. This decreases the likelihood that allergic skin disease was the sole cause of pruritus; instead, microneedling may have exacerbated a primary pruritic condition.

MN对人体的不良影响通常是一过性和轻微的，包括发红、疼痛、水肿、出血、瘙痒、肉芽肿反应和区域淋巴结肿大。在犬中，有过一过性发红伴出血的报道。在这项研究中，6只犬中的2只出现了瘙痒，这是人类头皮一种常见的副作用，但尚未在犬中报告过。其中一只犬(病例4)的瘙痒持续了大约两周，这归因于愈合，不需要额外的治疗。对于另一只瘙痒的犬(病例3)，由于手术前犬已经有轻度瘙痒，所以很难确定它是否是由MN引起的。然而，在MN手术后，犬立即出现了严重的抓痕。尽管如此，在12个月的监测期间，瘙痒并没有持续太久，也没有加重或导致抓痕。这降低了过敏性皮肤病是瘙痒的唯一原因的可能性;相反，微针可能加剧了原发性瘙痒。

 

A stronger sedation protocol was needed for treatment with 3 mm needles. This is consistent with the longer needles causing more immediate pain. Five of six dogs showed a depressed attitude for minutes to hours after the procedure. This might have been a result of pain, stress or residual medication effects. It was difficult to estimate the severity of pain in the present study as the only sign reported by the owners was discomfort after returning home. None of them felt that their dog required additional analgesic treatment. The mixed-breed dog did not exhibit any signs of pain.

使用3毫米针头治疗需要更强的镇静方案。这与较长的针头引起更直接的疼痛是一致的。6只犬中有5只在手术后的几分钟到几小时内表现出精神沉郁。这可能是疼痛、压力或药物残留作用的结果。在目前的研究中，很难估计疼痛的严重程度，因为宠主报告的唯一症状是回家后的不适。没有人觉得他们的犬需要额外的镇痛治疗。混血犬没有表现出任何疼痛的症状。

 

It should be noted that a small area (total 48cm2 , 16cm2 for each needle) was treated. In actual clinical settings, stronger anaesthetic and analgesic drugs may be required during and after the procedure, because typically a larger body area would be treated. Longer needles also cause more haemorrhage, erythema and oedema. Clinicians should be aware that this study was primarily designed to compare the efficacy of different needle lengths. Further research is needed to establish ideal anaesthetic and analgesic protocols.

需要注意的是，治疗面积较小(共48cm2，每针16cm2)。在实际的临床情况下，在手术过程中和手术后可能需要更强的麻醉和镇痛药物，因为通常需要治疗更大面积身体区域。长针也会导致更多的出血、发红和水肿。临床医师应该知道，本研究的主要目的是比较不同针头长度的疗效。需要进一步研究以建立理想的麻醉和镇痛方案。

 

Considering animal welfare, it is questionable whether MN should be the first-line treatment for HCA. It is primarily a cosmetic issue and the use of a painful therapy, requiring anaesthesia, should not be undertaken lightly. It is important to consider the noncosmetic importance of hair-coat functions, such as regulating body temperature, acting as a physical and immunological barrier, dispersion of sebum and pheromones, sensory perception, facilitation of social interactions and camouflage. The absence of hair can compromise the protective role of hair, putting affected individuals at an increased risk of skin damage and infection from various environmental stressors, including UV light, temperature extremes, micro-organisms and dehydration. Therefore, it is important to consider the potential consequences of hair loss when choosing treatments for HCA in dogs.

考虑到动物福利，MN是否应作为HCA的一线治疗值得商榷。这主要是一个美容问题，使用需要麻醉的疼痛疗法，不应该轻率地进行。重要的是要考虑到毛发功能的非美容重要性，例如调节体温、作为物理和免疫屏障、分散皮脂和信息素、感觉知觉、促进社会交往和伪装。没有毛发会损害毛发的保护作用，使患病动物面临各种环境压力源(包括紫外线、极端温度、微生物和脱水)造成的皮肤损伤和感染的风险增加。因此，在选择治疗犬HCA的方法时，考虑脱毛的潜在后果是很重要的。

 

All dogs showed hair regrowth after only one MN treatment and adverse reactions were transient. By contrast, medications for HCA have been minimally effective in most dogs. Furthermore, the medications (such as ketoconazole, trilostane, mitotane, deslorelin, medroxyprogesterone acetate, growth hormone and melatonin) utilised in the treatment of HCA are not without potential adverse effects. Because alopecia often relapses without continuous administration, long-term or life-long treatment might be needed. More substantial evidence from a larger number of cases with long-term evaluation for safety and efficacy is warranted. Until such evidence is available, caution is needed.

所有犬经1次MN治疗后毛发均再生，且不良反应短暂。相比之下，治疗HCA的药物对大多数犬的效果甚微。此外，用于治疗HCA的药物(如酮康唑、曲洛斯坦、米托坦、地洛瑞林、醋酸甲羟孕酮、生长激素和褪黑素)并非没有潜在的不良反应。由于脱毛经常复发，不持续用药，可能需要长期或终身治疗。需要更大样本量的证据，对其安全性和有效性进行长期评估。在获得这些证据之前，我们需要谨慎行事。

 

The cost of MN can vary depending on the selection of anaesthetic drugs and the labour cost of clinicians. In this context, using a roller product for MN proves to be a cost-effective option when compared to the expense of continuous treatment with medications. There is no definitive best treatment option available for HCA owing to ethical considerations, recurrence of alopecia, adverse reactions and the cost of prolonged therapies. Treatment decisions must take into consideration individual animal welfare, safety and efficacy.

MN的成本可以根据麻醉药物的选择和临床医生的劳动力成本而变化。在这种情况下，与持续使用药物治疗的费用相比，使用滚筒微针产品治疗被证明是一种具有成本效益的选择。由于伦理考虑、脱毛复发、不良反应和长期治疗的费用，HCA没有明确的最佳治疗方案。治疗决定必须考虑到个体动物的福利、安全性和有效性。

 

This study has some limitations. The sample size of six dogs is too low to draw broad conclusions on MN safety and efficacy. Variation in the pressure applied with the MN device is an inherent limitation. The treatments were performed by the same clinician in an effort to minimise this variation. Another limitation is that endocrinopathies were not ruled out. Although ACTH-stimulation test or low-dose dexamethasone suppression tests were not conducted, hyperadrenocorticism was not considered based on the young age, normal liver enzymes and absence of supportive clinical signs (polyuria, polydipsia and pot-bellied appearance). Hypothyroidism is similarly diagnosed by a combination of clinical signs, serum chemistry, TT4, fT4 and TSH tests. While none of the enrolled dogs showed any of these clinical signs or laboratory abnormalities, it is possible that some of the dogs might have had an underlying endocrinopathy that interfered with response to MN.

本研究有一些局限性。6只犬的样本量太小，无法就MN的安全性和有效性得出广泛的结论。MN装置施加的压力变化是一个固有的限制。治疗由同一名临床医师实施，以尽量减少这种差异。另一个局限性是未排除内分泌疾病。虽然未进行ACTH刺激试验或低剂量地塞米松抑制试验，但考虑到患犬年龄小，肝酶正常，无支持性临床症状(多尿、多饮、垂腹)，不考虑肾上腺皮质功能亢进。甲状腺功能减退症同样可以通过综合临床症状、血清化学、TT4、fT4和TSH检测来诊断。虽然没有犬显示任何这些临床症状或实验室异常，这可能是一些犬可能有潜在的内分泌疾病，干扰了对MN的反应。

 

CONCLUSIONS

总结

Optimal hair regrowth was obtained after MN with 3mm needles. Recurrence of alopecia occurred after 14–16 months. Future studies evaluating treatment of HCA in dogs should have a follow-up period of ≥18months to assess long-term success.

用3mm针MN后毛发再生效果最佳。术后14-16个月出现脱毛复发。未来评估犬的HCA治疗的研究应该有≥18个月的随访期来评估长期成功。

 

 

FIGURE 1 Photographs after microneedling (MN) procedure of Case 2. (a) Immediately after MN procedure. The treatment sites are divided into three areas: 1, 2 and 3mm needle are applied to each area, respectively, until capillary bleeding with erythema was noted. (b) An additional 3mm needle was applied after six weeks of MN, given that hair regrowth was more prominent in the 3mm sites. (c) Hair growth after threemonths. (d) Recurrence of hair loss after 15 months.

图1病例2微针(MN)术后照片(a) MN术后立刻拍照。治疗部位分为3个区域:每个区域分别使用1、2、3mm针，直至出现毛细血管出血伴发红。(b)在MN 6周后使用额外的3mm针，因为3mm部位的毛发再生更明显。(c)三个月后毛发生长。(d)15个月后脱发复发。

 

 

 

表1：六只毛囊周期停滞患犬MN治疗后皮肤镜信息

病例编号	特征	发病年龄	组织病理学检查	用药史
1	2岁已绝育雌性博美犬	8月龄	附件萎缩和毛囊角化症	曲洛斯坦2个月、褪黑素3个月
2	5岁已去势雄性博美犬	2岁	毛囊静止期增多和毛膜角化过多	褪黑素2个月
3	3岁已去势雄性博美犬	16月龄	附件萎缩和毛囊角化症	褪黑素1个月
4	2岁已绝育雌性博美犬	15月龄	毛囊静止期增多和毛膜角化过多	酮康唑3周、拖黑素8周
5	3岁已绝育雌性博美犬	2岁	N/A	拖黑素3个月
6	1岁已绝育雌性杂交犬	12月龄	毛囊静止期增多和毛膜角化过多	无

 

 

FIGURE 2 Bar graphs showing the hair growth assessment scale (1–4) after microneedling treatment. Longer needles result in more rapid hair growth.

图2柱状图显示微针治疗后毛发生长评估量表(1-4)。更长的针叶导致毛发生长更快。

 

 

FIGURE 3 Hair regrowth on ≤90% of the body after microneedling (MN) and recurrence of alopecia after 15 months (Case 1). (a) A Pomeranian dog with HCA before MN. (b) At three months after MN, hair regrowth was found in a wider area of the body. (c) Hair regrowth after six months. (d) Recurrence of hair loss after 18 months.

图3微针(MN)后≤90%的机体毛发再生，15个月后脱毛复发(病例1)。(a) MN前患HCA的博美犬。(b) MN后3个月，在更大面积的机体区域发现毛发再生。(c) 6个月后毛发再生。(d) 18个月后脱毛复发。

 

 

FIGURE 4 Adverse reactions after microneedling (MN). (a) Excoriation observed two weeks after the MN procedure. (b) Hair regrowth at self-traumatised sites observed two months after MN. (c) Global photograph of the patient immediately following MN treatment; three marked sites (1–3, and) indicate needle size (in mm). (d–f)×50 magnified photographs taken using a Folliscope suggest that longer needles cause more severe adverse reactions. (d) Minimal capillary bleeding and erythema observed with the use of a 1mm needle. (e) Bleeding, tissue erythema and mild oedema observed with the use of a 2mm needle. (f) Profound bleeding, erythema and oedema observed with the use of 3mm needles compared with shorter needles.

图4微针(MN)后的不良反应。(a) MN术后2周观察抓痕情况。(b) MN后2个月观察到的自损部位毛发再生情况。(c)患犬接受MN治疗后的全景照片;三个标记位点(1-3，和)表示针的大小(mm)。(d-f)×50使用Folliscope拍摄的放大照片表明，较长的针头会引起更严重的不良反应。(d)使用1mm针头观察到少量毛细血管出血和发红。(e)使用2mm针头观察到出血、组织发红和轻度水肿。(f)与使用较短的针相比，使用3毫米针时观察到严重出血、发红和水肿。

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