自体表皮移植术联合吡美莫司乳膏治疗白癜风疗效评价

目的:评价自体表皮移植术联合吡美莫司乳膏治疗稳定期白癜风的临床疗效。方法: 60例稳定期白癜风患者分为治疗组和对照组,所有患者均行单纯自体表皮移植术,治疗组痂皮脱落后外涂1%吡美莫司乳膏,每日2次。术后6个月评价皮损复色效果。结果: 治疗组有效率和痊愈率分别为93.3%和63.3%,明显高于对照组的70%和33.3%,差异有统计学意义(P<0.05)。结论:自体表皮移植术联合吡美莫司乳膏治疗白癜风疗效高于自体表皮移植。     

Topical pimecrolimus in the treatment of genital lichen planus: a prospective case series

BACKGROUND: A potent topical steroid is the conventional therapy for genital lichen planus (GLP). Side-effects or steroid resistance can be encountered and second-line therapy such as topical tacrolimus may be required. In our experience tacrolimus may be poorly tolerated in genital skin because of a burning sensation. In addition, there is impairment of Langerhans cell function, raising concerns about its long-term use. These adverse effects may not be as marked with pimecrolimus. To our knowledge, pimecrolimus has not been used in the treatment of GLP. OBJECTIVES: To assess the efficacy and tolerability of topical pimecrolimus in the treatment of GLP. METHODS: Eleven women with GLP were recruited: 10 had erosive vulval disease and one had classical lichen planus of perianal skin. Ten patients had poor disease control, and despite using topical steroids appropriately, two of these also had steroid-related side-effects in adjacent unaffected skin. The eleventh patient had adequate disease control but marked steroid atrophy. Topical pimecrolimus 1% cream (Elidel cream; Novartis, Camberley, U.K.) was applied twice daily to affected areas. Patients were followed up between 4 and 6 weeks later. They remain under regular review and at the time of writing mean follow-up is 5.2 months (range 2-10). RESULTS: Nine patients (82%) tolerated pimecrolimus, including three patients previously intolerant of tacrolimus. These nine patients showed a clinical response at 4-6 weeks: two showed a complete response with no residual disease activity visible and seven had a partial response. With longer follow-up, six (55%) of the women had a complete response and three (27%) were considered to have a partial response. Eight patients noted symptomatic improvement and one felt that her symptoms were the same as with steroid use. Two patients (18%) with erosive lichen planus were unable to tolerate pimecrolimus due to local irritation. CONCLUSIONS: We have found that topical pimecrolimus 1% cream is an effective treatment for GLP. Local irritation can limit its use, but it may be better tolerated than topical tacrolimus: three of our complete responders had previously been intolerant of tacrolimus. Topical pimecrolimus may be a valuable second-line treatment for patients with steroid-related side-effects or steroid-resistant GLP.     

Topical pimecrolimus and tacrolimus do not accelerate photocarcinogenesis in hairless mice after UVA or simulated solar radiation

Abstract:  Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed specifically for the treatment of atopic eczema. Experience with long-term use of topical calcineurin inhibitors is limited and the risk of rare but serious adverse events remains a concern. We have previously demonstrated the absence of carcinogenic effect of tacrolimus alone and in combination with simulated solar radiation (SSR) on hairless mice. The aim of this study is to determine whether pimecrolimus accelerates photocarcinogenesis in combination with SSR or pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice ( n  = 275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED) or UVA (25 J/cm²) 3–4 h later. This was done up to 365 days in the SSR-treated groups and up to 500 days in the UVA-treated groups. Pimecrolimus did not accelerate the time for development of the first, second or third tumor in any of the groups. Median time to the first tumor was 240 days for the control-2SED group compared with pimecrolimus-2SED group (233 days), control-4SED group (156 days) compared with pimecrolimus-4SED group (163 days) and control-6SED group (162 days) compared with pimecrolimus-6SED group (170 days). Only one mouse in each of the three UVA groups developed a tumor. We conclude that pimecrolimus in combination with SSR and both pimecrolimus and tacrolimus in combination with UVA do not accelerate photocarcinogenesis in hairless mice.     

Unsuccessful treatment of extragenital lichen sclerosus with topical 1% pimecrolimus cream

Lichen sclerosus most commonly affects the anogenital region. Spreading into the extragenital regions is rare, and its course is most commonly asymptomatic. Women have been reported to be affected 6 to 10 times more often than men. The etiology of lichen sclerosus is still unknown. The disease is characterized by ivory-white atrophic plaques, and no treatment ensuring complete recovery is available. T-cells are also involved in its pathogenesis. Pimecrolimus is a topical inhibitor of T-cells. In the present paper, we present a male patient with lichen sclerosus located only in extragenital regions and report an unsuccessful outcome of treatment with pimecrolimus 1% cream administered topically twice a day for 16 weeks.     

308nm准分子光联合吡美莫司乳膏治疗白癜风疗效观察

目的：评价308 nm准分子光联合吡美莫司乳膏治疗白癜风的疗效和安全性.方法：将150例白癜风患者随机分为3组.治疗组50例,采用308 nm准分子光联合1%吡美莫司乳膏治疗.对照1组50例,采用NB-UVB联合1%吡美莫司乳膏治疗.对照2组50例,单纯外用1%吡美莫司乳膏治疗.3组均连续治疗12～24周,进行临床疗效和不良反应评价.结果：治疗组有效率为92.0%,对照1组为74.0%,对照2组为50.0%.3组患者均未出现严重不良反应.结论：308 nm准分子光联合吡美莫司乳膏治疗白癜风疗效确切,安全性好.     

外用1%吡美莫司乳膏治疗白癜风临床疗效观察

【摘要】：目的：观察局部外用1%吡美莫司乳膏治疗白癜风的临床疗效及安全性。方法：给予49例白癜风患者1%吡美莫司乳膏,每日2次外用,每两个月随访一次,观察治疗后靶皮损复色情况。结果：49例患者共计53处皮损,外用1%吡美莫司乳膏4-6个月后,22例达到不同程度的复色,有效率为55.10％,显效率为22.45%。除了2例患者用药后出现面部痤疮,其它无任何不良反应。结论：局部外用1%吡美莫司乳膏治疗白癜风疗效较好,不良反应少。     

外用他克莫司和吡美莫司的安全性

他克莫司和吡美莫司是新型钙调磷酸酶抑制剂药物,其外用制剂可用于治疗特应性皮炎。近年来,对这两种药物的安全性存有争议。现有的资料表明,外用他克莫司和吡美莫司安全性高,不引起皮肤萎缩,经皮吸收极少,无明显的系统免疫抑制作用,不会引起皮肤或系统的感染和肿瘤的发病率升高。     

Liposomal tacrolimus lotion as a novel topical agent for treatment of immune-mediated skin disorders: experimental studies in a murine model

BACKGROUND: Systemic but not topical tacrolimus (TAC) is effective against psoriasis. Mechanical methods that enhance skin penetration by TAC increase its topical antipsoriatic effect. Liposomal delivery of TAC would increase its penetration of skin, allow for slow release and diminish its toxicity. OBJECTIVES: To test a liposomal TAC (LTAC) formulation in a murine model. METHODS: Drug penetration was assessed using radiolabelled LTAC, and the effect of TAC and LTAC on Balb/c skin graft survival and on ovalbumin-induced delayed-type hypersensitivity reactions was tested in C57BL/6 mice. RESULTS: Radiotracer studies showed that topical application of LTAC achieved nine times the concentration of TAC at a target site than did systemic administration of TAC. Combination of systemic and topical LTAC significantly increased mean +/- SD skin graft survival (14.8 +/- 1.5 days) compared with systemic TAC (8.0 +/- 0.7 days) and control mice (8.4 +/- 1.2 days). LTAC was more effective systemically than TAC in the prevention of delayed-type hypersensitivity reactions. Topical LTAC also prevented this response. CONCLUSIONS: Topical LTAC was effective in this model of immune-mediated skin disease. Because LTAC achieves higher skin concentrations than systemic TAC it may be an effective delivery system for TAC in the treatment of psoriasis.     

Erosive mucosal lichen planus: response to topical treatment with tacrolimus

Erosive mucosal lichen planus is a painful and disabling inflammatory skin disease that is highly resistant to topical treatment. We report on six patients with severe recalcitrant erosive mucosal lichen planus who benefited from topical application of tacrolimus ointment. After 4 weeks of treatment, complete resolution was observed in three cases, and substantial improvement was achieved in the other three patients. In these cases, prolonged treatment resulted either in further improvement or in complete healing. All patients reported rapid relief from pain and burning. No severe side-effects were observed.     

Clinical effects of topical pimecrolimus in a patient with Fox-Fordyce disease

Fox-Fordyce disease (FFD) is characterized by a pruritic eruption of skin-coloured or yellowish papules in areas rich in apocrine glands. The histology comprises dilatation of follicular infundibula with hyperkeratosis, acanthosis, and spongiosis of the infundibular epithelium with perifollicular infiltration of lymphocytes and foamy histiocytes. We treated a 12-year-old girl with FFD with topical pimecrolimus for 12 weeks, this resulted in a complete clearance of lesions. After the therapy, the patient was followed for an additional 19 months without signs of relapse. The effects of pimecrolimus in FFD might imply that an inflammatory process inducing secondary reactive hyperkeratosis could be involved in the pathogenesis of FFD.     

Trichomegaly induced by topical tacrolimus for the treatment of periorbital vitiligo: A brief report of a new adverse effect

Trichomegaly is a known adverse effect of systemic administration of cyclosporine but is less commonly associated with systemic tacrolimus or with topical calcineruin inhibitors. In this report, we describe the first case, to our knowledge, of trichomegaly due to long‐term use of topical tacrolimus for periocular vitiligo.     

Pimecrolimus cream 1%: A new development in nonsteroid topical treatment of inflammatory skin diseases

Atopic dermatitis (AD) is one of a family of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and allergic contact dermatitis). Dermal inflammation and production of proinflammatory cytokines by activated T cells is a prominent and defining characteristic in all of these conditions. Corticosteroids, though effective and potent immunosuppressants, are associated with a number of systemic and local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981) is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1% is minimally absorbed into the circulation; thus, it has a low bioavailability-reducing the risk for systemic adverse effects. The efficacy and safety of pimecrolimus cream 1% has been well shown in diverse patient populations with inflammatory skin diseases in several well-controlled trials. Significant and rapid amelioration of the signs and symptoms of AD was established in 3 studies lasting 6 weeks each, evaluating 589 pediatric patients. In a 1-year study, pimecrolimus was applied at the first signs and symptoms of eczema to prevent the progression of AD to flares. Flares were prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or completely eliminating the need for topical corticosteroids during a 1-year treatment period. Results in pimecrolimus studies in chronic irritant hand dermatitis and chronic hand dermatitis of mixed causes indicate potential for use in these important diseases, and further study in these indications is warranted.     

特应性皮炎皮损HSP70的表达及他克莫司对其表达的影响

目的:探讨热休克蛋白(HSP)70在特应性皮炎(AD)中的表达及外用他克莫司对HSP70表达的影响。方法:采用免疫组化二步法检测8例中至重度AD患者急性发作期炎性皮损HSP70表达及外用0.1%或0.03%他克莫司软膏治疗AD3周后HSP70表达的变化。结果:免疫组化检测显示HSP70在AD急性发作期炎性皮损角质形成细胞(KC)的胞核,胞浆及胞膜外过度表达,其中在3例大面积泛发或红皮病型急性AD皮损KC中,HSP70以弥漫性细胞核表达伴胞浆表达为特征,主要定位于基底层至颗粒层;外用他克莫司软膏治疗3周后特应性皮炎皮损KCHSP70的核表达消失,胞浆及膜(表面)表达信号减弱。结论:急性期AD皮肤KC的HSP70过度表达;他克莫司可通过直接或间接作用抑制KC的HSP70诱导性或过度表达,从而可抑制或下调与内源性HSP70危险信号有关的AD皮肤天然自身免疫炎症反应。     

Granuloma faciale: a case report on long-term treatment with topical tacrolimus and dermoscopic aspects

Granuloma faciale (GF) is an uncommon, benign form of chronic leukocytoclastic vasculitis, which predominantly affects the face and which is notoriously resistant to several therapies. Besides a range of therapeutic modalities, tacrolimus has been recently reported in the successful treatment of GF. Herein we describe the clinical, dermoscopic and histopathological findings in a patient affected by GF and its response to long-term topical treatment with tacrolimus 0.1% cream.     

The use of topical calcineurin inhibitors in lupus erythematosus: an overview

Lupus erythematosus (LE) shows a broad range of cutaneous symptoms, including acute, subacute and chronic lesions. The gold standard of established topical treatment consists of medium‐ to high‐potency corticosteroids. Because face and neck are often involved, adverse effects of prolonged corticosteroid use are not uncommon. There is a need of steroid‐free topical treatment in LE. With the development of topical calcineurin inhibitors, tacrolimus and pimecrolimus, there is an alternative available. The present study reviews the literature data on topical tacrolimus and pimecrolimus for malar rash, subacute lesions and discoid chronic lesions among others. The present data argue for an efficacy of these compounds in acute and subacute cutaneous LE manifestations with a rapid response and only minor side‐effects when used as an adjunct to systemic treatment. In chronic discoid LE, hypertrophic plaques do not well respond because of limited penetration. The primary target seems to be the decrease or blocking of cytokine production by activated T lymphocytes.     

他克莫司软膏联合308 nm准分子激光治疗白癜风临床疗效观察

目的：评价0．1％和0．03％他克莫司软膏联合308nm准分子激光治疗对紫外线治疗抵抗的白癜风皮损的疗效与安全性。方法：采用随机、自身对照的临床试验，每例患者选取紫外线治疗抵抗区域的皮损，随机选取躯体一侧皮损为治疗侧，采用他克莫司软膏联合308nm准分子激光治疗；另一侧为对照侧，仅用308nm准分子激光治疗。2个月后进行疗效判定。结果：联合治疗组有效率为89．0％，对照组为71．6％，两组间疗效比较差异有统计学意义（P〈0．05）。结论：他克莫司软膏联合308nm准分子激光治疗白癜风起效快，疗效好。