Patients with vitiligo, a skin disorder characterized by patches of white, or de-pigmented skin, had better repigmentation of these patches when they were treated with a combination of laser therapy and tacrolimus ointment than patients treated with laser therapy alone, according to a new study.
    据一项最新的研究表明应用激光和他克莫司软膏可以更好的治疗白癜风——表现为白人或有色人种皮肤上混乱的色素斑块。

    Vitiligo is a skin pigmentation disorder that affects 1-2% of people worldwide. Patients with vitiligo develop white patches on their skin, referred to as "lesions." Recently, the 308-nm excimer laser has been used to treat lesions associated with vitiligo with good results. Additionally, a new topical ointment called tacrolimus has shown promise in treating vitiligo.
    白癜风的全球发病率为1-2%。白癜风患者皮肤上的斑块也被认为是一种皮损。最近, 308准分子激光治疗白癜风获得良好的结果。另外,一支种叫tacrolimus局部用药软膏在治疗白癜风时显露不凡的效果。
    Thierry Passeron, MD, of Hopital de l'Archet, Nice, France, and colleagues investigated the effects of the 308-nm excimer laser in combination with tacrolimus on 14 patients with vitiligo aged 12-63 years. Their findings were published in the Archives of Dermatology.
    法国尼斯I'Archet医院皮肤科Thierry Passeron医师和同事对14位年纪在12－63岁的患者进行308nm激光联合tacrolimus的白癜风的治疗。研究报告发表在Archives of Dermatology.
    For each patient, 4-10 lesions were chosen and treated twice a week with the 308-nm excimer laser for a total of 24 sessions. Topical 0.1% tacrolimus ointment was applied twice daily to target lesions for patients in group A (excimer laser plus tacrolimus). Patients in group B received only the laser treatments. Treated lesions were compared with control lesions (that received no treatment) on the opposite side of the body. Forty-three lesions were treated (23 in group A and 20 in group B).
    所有患者的4-10处皮损均接受了每周两次共计24次的308准分子激光治疗。其中准分子激光联合tacrolimus的A组，每天使用0.1%的tacrolimus药膏两次。B组仅接受激光的治疗。治疗的皮损与患者身上未治疗的皮损做对照研究。共有43处皮损接受治疗，其中A组23处，B组20处。
    The researchers observed repigmentation in all group A lesions (100%) and in 17 (85%) of the 20 group B lesions. Repigmentation was not observed in the control lesions.
    研究人员观察到A组的皮损均获得复色的改善，B组20处皮损中有在17处 (85%)有复色改善。未治疗的区域没有看到复色的改善。
    "A repigmentation rate of 75% or more was obtained in 16 (70%) of the 23 group A lesions and in 4 (20%) of the 20 group B lesions," the authors wrote. The average number of sessions needed to see an improvement in repigmentation was 10 for group A and 12 for group B.
    A组的复色率在75% 或更多的的皮损为16处 (70%)，而B组则为4处 (20%)。 获得重要改善的平均疗程A组和B组分别为10次 和12次。
    "The combination of 0.1% tacrolimus ointment applied twice daily and 308-nm excimer laser therapy performed twice a week gives excellent results on UV-sensitive and UV-resistant areas. The treatment was well tolerated, and the patients were satisfied," the researchers concluded (Arch Dermatol, 2004;140:1065-1069; (www.archdermatol.com).
    研究人员指出，结合0.1%的tacrolimus软膏每天2次，以及308－nm的准分子雷射疗法每周2次对于UV敏感的或是不敏感的区域有绝佳的效果；治疗的耐受非常好，患者非常满意。
This article was prepared by Medical Devices & Surgical Technology Week editors from staff and other reports. Copyright 2004, Medical Devices & Surgical Technology Week via NewsRx.com & NewsRx.net

    Sept. 21, 2004 - 根据一项发表于9月号皮肤学学志上的比较性、前瞻性、随机分派、个体间早期试验结果显示，结合0.1%局部tacrolimus软膏与308－nm准分子雷射在治疗对紫外线（UV）治疗无效的白斑病灶上比单独雷射治疗更有效。
    法国尼斯I'Archet医院皮肤科Thierry Passeron医师指出，窄频（NB）－UV－B被认为是治疗广泛性白斑最佳的治疗；根据研究人员表示，UV－B疗法被认为透过对黑色素细胞与角质细胞分泌的细胞激素的直接作用，而刺激黑色素细胞转移，以及从发囊凹处增殖。

    研究人员指出，最近对于白斑自体免疫来源的实验，也强调了UV疗法的免疫抑制作用对于白斑再色素化可能的应用；Tacrolimus，一种新的局部免疫抑制药物，被开发用于治疗异位性皮肤炎，已经被两项前瞻性试验受瞩目的结果证实可以治疗白斑。

    为了确定结合雷射治疗与免疫抑制方式的效果，研究人员征集14位受试者，年龄从12到63岁，患有Fitzpatrick皮肤类型II到VI的、而且有白斑至少3个月以上的患者；总共有43个白斑病灶被随机分派接受每周两次的308－nm准分子雷射治疗持续六周，或是雷射治疗加上0.1%局部tacrolimus软膏每天涂抹两次（双重治疗组）；治疗后的病灶再与受试者另外一边未接受治疗的病灶相比较。

    起初的雷射剂量是12 mcal／cm2（50 mJ／cm2），低于使用于白斑皮肤最低的引起红肿的剂量，而且每个接受隔次治疗时将剂量加到12 mcal／cm2。试验主要终点是治疗效果，定义为再色素化超过75%。

    6周后的结果显示这两种治疗相较于控制组，对于再色素化有显著的效果（P＜.001）；所有病灶（100%）以双重治疗（共23位）的结果显示再色素化，相较于单独雷射治疗（共20位）的85%，双重治疗组相较于单独雷射治疗再色素化地比较快（10次治疗相较于12次治疗）。

    双重治疗组达到75%以上再色素化的病灶比例比雷射单独治疗多（70%相较于20%，P＜.001）。

    双重治疗组对于UV治疗无效的区域（例如骨质为主的部位）相较于单独治疗组（60%相较于0%，P＜.002）有更高的治疗成功率，但是在两组治疗对UV敏感的位置，例如脸部、躯干、与四肢没有明显的差异（77%相较于57%，P＝.61）。

    治疗反应被发现与病灶位置有关：对UV敏感的病灶相较于对UV没有敏感性的病灶产生反应的程度更高（P＝.004）；对于治疗反应与年龄（P＝.73）、性别（P＝.39）、皮肤种类（P＝.17）或是最低引起红肿的剂量（P＝.72）之间没有关系。

    此外，研究也发现，对治疗的耐受性是很好的；不良反应包括中度至严重的红肿，每位病患至少发生一次，以及罕见的大泡性病灶（每组有两个病灶），36%的病患因为tacrolimus软膏发生中度的刺痛。

    研究人员指出，结合0.1%的tacrolimus软膏每天2次，以及308－nm的准分子雷射疗法每周2次对于UV敏感的或是不敏感的区域有绝佳的效果；研究人员也指出，需要监视试验（有控制组的）以及更大的样本数目来确认这些早期试验结果。
    Excimer Laser Plus Tacrolimus Ointment Effective in UV-Resistant Vitiligo
By Yael Waknine
Medscape Medical News
    Sept. 21, 2004 — Combination therapy with topical 0.1% tacrolimus ointment and the 308-nm excimer laser is significantly more effective than laser monotherapy in the repigmentation of ultraviolet (UV)-resistant vitiliginous lesions, according to the results of a comparative, prospective, randomized, intra-individual preliminary study published in the September issue of the Archives of Dermatology.
    "Narrowband (NB)-UV-B therapy is considered the best treatment for extensive vitiligo vulgaris," write Thierry Passeron, MD, from the Department of Dermatology at the H?pital de l'Archet in Nice, France, and colleagues. According to the authors, UV-B therapy is thought to stimulate melanocytic migration and proliferation from the niches located in hair follicles through direct action on melanocytes and the actions of cytokines secreted by keratinocytes.
    "Recent studies on the autoimmune origin of vitiligo also emphasize the probable implication of the immunosuppressive action of UV therapy in the repigmentation of vitiliginous plaques," the authors note. "[T]acrolimus, a new topical immunosuppressive drug developed for the treatment of atopic dermatitis, has shown some interesting results in treating vitiligo in 2 prospective studies."
    To determine the effectiveness of combining laser therapy with an immunosuppressive approach, the investigators recruited 14 subjects, aged 12 to 63 years, with Fitzpatrick skin types II to IV and having had vitiligo for a minimum of three months. A total of 43 vitiliginous lesions were randomized to receive either 308-nm excimer laser monotherapy twice weekly for six weeks or the laser sessions plus topical 0.1% tacrolimus ointment applied twice daily (dual therapy group). Treated lesions were matched with untreated lesions (controls) on the subjects' opposite side.
    Initial laser dose was 12 mcal/cm2 (50 mJ/cm2) less than the minimal erythemal dose in vitiliginous skin, and fluences were increased by 12 mcal/cm2 at every second session. The primary outcome was treatment efficacy as defined by lesion repigmentation of 75% or greater.
    Results at six weeks showed both treatments to have had a significant effect on repigmentation compared with controls (P < .001 for each). All lesions (100%) treated with dual therapy (n = 23) showed repigmentation compared with 85% of those treated with laser monotherapy (n = 20). Lesions in the dual therapy group had a quicker onset of repigmentation compared with the monotherapy group (10 sessions vs. 12 sessions).
    The percentage of lesions achieving repigmentation of 75% or greater was significantly higher in the dual therapy group compared with the monotherapy group (70% vs. 20%; P < .001).
    The dual therapy group also showed a significantly higher rate of treatment efficacy for lesions in UV-resistant areas (eg, bony prominences) compared with the monotherapy group (60% vs. 0%; P < .002), but no statistical difference was found between the two treatments in UV-sensitive areas such as the face, neck, trunk, and limbs (77% vs. 57%; P = .61).
    Treatment response was found to be related to lesion locale: UV-sensitive lesions responded to a significantly greater degree than did UV-resistant lesions (P = .004). No association was found between response to treatment and age (P = .73), sex (P = .39), skin type (P = .17), or minimal erythemal dose (P = .72).
Treatment was well tolerated. Adverse events included moderate to severe erythema occurring at least once in each patient and rare bullous eruptions (two lesions in each group). Moderate stinging due to tacrolimus ointment application occurred in 36% of patients.
    "The combination of 0.1% tacrolimus ointment applied twice daily and 308-nm excimer laser therapy performed twice a week gives excellent results on UV-sensitive and UV-resistant areas," the authors write. "A monitored study (with controls) on a larger population would be in order to confirm these encouraging preliminary results."
The authors report no pertinent financial disclosures.
Arch Dermatol. 2004;140:1065-1069
Reviewed by Gary D. Vogin, MD
    Combination Tx combats vitiligo: novel Tx for vitiligo combines excimer laser, tacrolimus.(Pigmentary Disorders)
    Dermatology Times,  November, 2003  by Gagnon, Louise
    New Orleans - Combination therapy has proven effective in treating vitiligo in a small number of patients, according to research presented at the annual meeting of the American Society of Dermatologic Surgeons, held here last month.
    In a pilot study of eight patients, about half of the vitiliginous patches were treated with excimer laser and     placebo while the other half were treated with excimer laser and topical tacrolimus ointment (0.1 percent), with the latter treatment leading to quicker resolution. An acquired skin disorder characterized by symmetric white patches, vitiligo affects about 1 to 2 percent of the population, according to the study's principal investigator.
    Topical Immunomodulators
    The standard treatment for vitiligo has been phototherapy, but recent research has pointed to topical immunomodulators because they suppress dysregulated aspects of the immune system. While vitiligo is a condition that originates from immunological irregularities, the exact pathogenesis of the condition is not known. Some studies have pointed to genetic predisposition, its relationship to autoimmune disorders, biochemical and neurohormonal imbalance, as well as environmental toxins and stressors.
    Some research has pointed to tacrolimus and sunlight being an efficacious combination, which prompted Adam Kawalek and colleagues to undertake the comparative study. Subjects who had rapidly progressing disease, evidence of spontaneous repigmentation, or treatment for their vitiligo in the last six months were not included in the study.
    Treatment Concerns
One of the primary concerns with the use of phototherapy is exposure to ultraviolet radiation, and the increased risk of skin cancer because of these treatments. Using the excimer laser is essentially targeted phototherapy because only affected skin is exposed to the radiation. The excimer laser has demonstrated a quicker therapeutic effect compared to conventional phototherapy. Administered in combination with a topical immunomodulator such as tacrolimus will hasten the results and therefore reduce radiation exposure.
"The addition of tacrolimus reduces the total treatment time and the amount of treatments needed," said Kawalek, a third-year medical student at Mount Sinai Medical School. "On average, the number of treatments is reduced by three. It also represents a cost savings to the patient."
    Research Study
    A total of 20 patches from six to eight patients qualified for evaluation in the study. Two of the initial 10 patients didn't adhere to the treatment regimen and were excluded from the study. Of the 20 patches, eight were located proximally and 12 were located on the extremities, which are knees, wrists, and elbows.
All patches that were selected received excimer laser treatments three times a week for 24 treatments over a period of 10 weeks. Topical tacrolimus and placebo were applied to randomized patches twice daily throughout the trial.
    Photographs were taken of all vitiliginous patches at baseline, every two-week period throughout the trial, and at six-months post treatment. Repigmentation was graded on a four-point scale with 0 indicating no response, 1 indicating minimal response or 25 percent or greater repigmentation, 2 indicating moderate repigmentation, that is anywhere from 25 to 75 percent, 3 indicating marked or 75 percent or greater repigmentation, and 4 indicating complete or 100 percent repigmentation.
    Research Results
    A total of 50 percent of patches that were treated with combination therapy responded well to the treatment, defined as a score of 3 or greater. By contrast, just 20 percent of patches that were exposed to laser treatments alone achieved that level of improvement.
    "It's important to get these data out there," said Kawalek. "Physicians can now know that they can enhance the     performance of the excimer laser with combination therapy."
    There were no serious side effects that were reported, but there was some initial stinging and burning when the tacrolimus ointment was first applied, which subsided after several days of treatment. Mild-to-moderate erythema was observed in all patches, and one patch had some blistering, forcing the laser treatment to be discontinued until that adverse event subsided.
    In three of the six subjects, hyperpigmentation was witnessed on skin patches that were treated with combination therapy for a transient period, about three weeks. The patches regressed to normal skin tone, hinting at these subjects having normal melanocyte function.
    Researchers did not perform long-term follow up to determine if the effect was permanent, but noted that experience with narrowband UVB treatment has shown that repigmentation is permanent.
    Repigmentation Therapy


    Hypopigmentation patients limit toxic exposure with UV Laser Tx

Dr. Lee

    New Orleans - Treatment with an ultraviolet laser system for hypopigmentation is more effective and protective against possible toxicity than standard photodynamic therapy, according to a study presented at the annual meeting of the American Society for Dermatologic Surgeons and the American College of Mohs Micrographic Surgery and Cutaneous Oncology here last month.
A three-arm, one-year study compared treatment of 15 patients with vitiligo, 20 patients with hypopigmented striae, and 15 patients with hypopigmented scars using the Relume UV system made by Lumenis. There were control sites selected for patients with vitiligo and those with hypopigmented striae.
    Patients received a weekly dose of 290 nm to 320 nm of the Relume UV system. Before the administration of the ultraviolet radiation, minimal erythematous dose tests were performed, and a starting dose of MED was administered at the first treatment session. Patients received a maximum of 16 treatments and were followed for six months after their last treatment. Digital photographs were taken to document the progression in body areas where there was initial hypopigmentation.
    The technology's wavelengths are designed to activate dormant melanocytes surrounding the hair follicles by increasing numbers of and movement of melanocytes toward the upper levels of skin, explained Min-Wei Christine Lee, M.D., the study's principal investigator and a clinical instructor at the University of California, San Francisco.
    "These are patients who have some pre-existing melanocytes," said Dr. Lee, a dermatologic surgeon and director of The East Bay Laser & Skin Care Center in Walnut Creek, Calif. "If all their melanocytes are dead, there is no way to restimulate repigmentation. That is the case with severe vitiligo. The technology would not be effective in that case."
    The results show promise that patients can limit potentially toxic exposure to ultraviolet radiation, Dr. Lee said. The treatment is contraindicated in pregnancy and for patients who are deemed to be too photosensitive, for they may be unable to tolerate it.

Ultraviolet laser systems treat hypopigmentation well (before left, after right), and are said to be protective against possible toxicity. (Photos courtesy of Min-Wei Christine Lee, M.D.)

    In the comparative study, the amount of repigmentation ranged from 20 percent to 70 percent. Specifically, 12 percent of 15 patients showed some repigmentation, ranging from 20 percent to 70 percent; 18 of 20 patients with hypopigmented striae showed some repigmentation, ranging from 30 percent to 70 percent; and seven of 15 patients with hypopigmented scars showed some degree of repigmentation, ranging from 20 percent to 50 percent.
    More than 50 percent of all patients with vitiligo who had repigmentation experienced regression, indicating that repigmentation could not be sustained. That finding is comparable to those found with conventional phototherapy and treatment with the excimer laser, according to Dr. Lee. More studies need to be conducted to determine the frequency of treatments and intervals between treatments to maintain the improvement, she added.
    The reduction in number of treatments also represents a significant cost savings to the patient, Dr. Lee said, noting a treatment can cost anywhere from $150 to $550 depending on the size of the patches on the body. The technology, light in weight and designed to be portable for transport, is one that is very easy to use for the practitioner.