Topical tacrolimus as a therapeutic adjunct in patients with cutaneous lupus erythematosus. A report of three cases

The topical therapy of cutaneous lupus erythematosus (LE) consists mainly of corticosteroids which may lead to significant side effects when overused. We report the efficacy of topical tacrolimus as a therapeutic adjunct in 3 patients with cutaneous LE of the face. All patients, 1 with systemic LE and a malar rash, 1 with annular subacute cutaneous LE, the other with a papular variant of subacute cutaneous LE, experienced significant improvement following application of tacrolimus ointment. Treatment with topical tacrolimus was tolerated well without major side effects in all patients. The presented cases are in line with recent reports that topical tacrolimus may be effective in facial LE.     

Safety information for tacrolimus: present and future

In this article there were regarded the most frequent side effects that appear in the patients who have been treated with topical tacrolimus, and the association between topical tacrolimus and the development of tumors is unfolded. The irritation in the site of application of the tacrolimus can manifiest as pruritus, sensation of burning and/or eritema located to the area of the application. It is the most frequent side effect, independently of the duration of the study. The cutaneous infections, especially the viral ones, tend to be more numerous in patients with atopic dermatitis that receive topic tacrolimus. After reviewing the medical literature one concludes that nowadays there doesn t exist scientific evidence of an increase of skin cancer, lymphomas or systemic immunosuppression in those patients that use or have used topical tacrolimus. Nevertheless, it is not possible to exclude the possibility that there appear cutaneous and/or systemic long-term side effects.     

Topical treatment of perianal eczema with tacrolimus 0·1%

Summary Background Perianal eczema is an inflammatory skin disease with a high prevalence in most industrialized countries. As general practitioners and dermatologists frequently see patients with perianal eczema the need for efficient, fast and safe therapies is high. Topical calcineurin inhibitors such as tacrolimus (FK506) ameliorate cutaneous inflammation and associated pruritus in an array of inflammatory dermatoses. Objectives To investigate the effect of topical tacrolimus in perianal eczema. Methods Twenty‐four patients with perianal eczema were treated with tacrolimus 0·1% ointment twice daily on the affected skin area for 2 weeks. Results All returning patients showed clinical improvement as assessed by macroscopic appearance and clinical score (modified SCORAD index). Conclusions In this short‐term trial we demonstrate that topical tacrolimus 0·1% is safe, efficient and well tolerated in patients with perianal eczema irrespective of the underlying cause.     

Topical calcineurin inhibitors in the treatment of atopic dermatitis - an update on safety issues

Atopic dermatitis is a common chronic skin disorder whose management is complex. Topical corticosteroids have been the mainstay of atopic dermatitis treatment for more than 50 years but have multiple side effects. Topical calcineurin inhibitors including tacrolimus and pimecrolimus are safe and efficacious in atopic dermatitis. In 2005 the FDA issued "black box" warnings for pimecrolimus cream and tacrolimus ointment because of potential safety risks, including skin cancers and lymphomas. However, these concerns are not supported by current data. Topical calcineurin inhibitors are particularly indicated for treating patients with atopic dermatitis in whom topical corticosteroid therapy cannot be employed or may cause irreversible side effects. They can be used advantageously in problem zones. A novel regimen of proactive treatment has been shown to prevent, delay and reduce exacerbations of atopic dermatitis. Therapy with topical calcineurin inhibitors should be managed by an experienced specialist and each patient should receive proper education on how to use them and what possible unwanted effects may be expected.     

Topical tacrolimus significantly promotes repigmentation in idiopathic guttate hypomelanosis: a double‐blind,randomized, placebo‐controlled study

Background  Idiopathic guttate hypomelanosis (IGH) is an idiopathic disorder affecting a large number of people. Effective treatments are not yet available. Objectives  To investigate the efficacy of topical 0.1% tacrolimus ointment compared with placebo in the treatment of IGH. Materials and methods  Twenty‐six patients were included in the study. Lesions on one side of the body were selected to have a treatment with 0.1% tacrolimus ointment, whereas those on the other side served as a control with placebo ointment that had the same physical appearance. Colorimeter was used to assess skin colour at baseline and at 1, 2, 3, 4 and 6 months of treatment. Results  Mean luminosity scale after adjusted for baseline from the treated side gradually decreased and reached statistical significance compared with the control group after 6 months of treatment (P = 0.019). Physicians’ improvement grading score showed that 11% of the patients demonstrated improvement of their skin lesions on the treated side after 6 months’ treatment. Conclusion  Topical 0.1% tacrolimus ointment appeared to be an effective and safe treatment for IGH. The improvements were best observed by colorimetry, yet, they were not statistically significant upon clinical assessments.     

A case of Darier''s disease successfully treated with topical tacrolimus

Tacrolimus is a macrolide that inhibits T-cell activation. The most extensive experience with topical tacrolimus has been in treating atopic dermatitis but it has been used in various skin diseases, including Hailey-Hailey disease, with encouraging results. We report a case of extensive Darier's disease successfully treated with topical tacrolimus, after suspension of oral isotretrinoin due to major depression.     

Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin

BACKGROUND: Tacrolimus, produced by the fungus Streptomyces tsukabaensis, is a potent macrolide immunosuppressant widely used in liver and kidney transplantation. Topical tacrolimus has recently been found to be an effective treatment for atopic dermatitis (AD). OBJECTIVES: Because of the well-known association between T-cell immunosuppression and an increased risk of carcinogenesis, we investigated the effect of topical tacrolimus on skin carcinogenesis in 117 mice. METHODS: Approximately 8 cm2 of the shaved dorsal skin of 7-week-old female CD-1 mice was treated with 7,12-dimethylbenz[alpha]anthracene (DMBA) dissolved in acetone, which is in general use as a tumour initiator, or acetone alone, on day 1 of the experiment, followed by promoting treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) with or without tacrolimus, or acetone with or without tacrolimus, for 20 weeks. The mice were divided into six treatment groups: (1) DMBA followed by acetone; (2) DMBA followed by TPA; (3) DMBA followed by acetone + tacrolimus; (4) DMBA followed by TPA + tacrolimus; (5) acetone followed by acetone + tacrolimus; and (6) acetone followed by acetone (control). RESULTS: The induction of skin tumours was significantly greater in the TPA-treated groups than in the absence of TPA. However, after 14 weeks there was marked synergy between tacrolimus and the DMBA/TPA regimen, with 0.47 +/- 0.13 (mean +/- SD) new tumours per mouse per week in group 4 vs. 0.10 +/- 0.025 in group 2 (P < 0.01), and 0.01 +/- 0.002 in group 3. A significant reduction in the CD4/CD8 ratio was found in axillary and inguinal lymph nodes in tacrolimus-treated mice, supporting the presumption that the immunosuppressive effect of the drug was responsible for its effect in promoting tumorigenesis. The major increase in tumours caused by topical tacrolimus was of papillomas, not squamous cell carcinomas. Papillomas are uncommon in humans, and are benign. However, 8.5% of the tumours found in the experiment were squamous cell carcinomas, and a considerable synergy between topical tacrolimus and conventional carcinogens was observed, raising the spectre of some risk of skin carcinogenesis in AD patients undergoing prolonged treatment with tacrolimus. CONCLUSIONS: Caution and careful surveillance are required with regard to skin lesions in patients treated with tacrolimus for prolonged periods.     

Efficacy of photodynamic therapy with topical 5‐aminolevulinic acid using intense pulsed light for Bowen’s disease

Photodynamic therapy (PDT) with topical 5‐aminolevulinic acid (ALA) is reported to be an effective and safe treatment for superficial non‐melanoma skin cancers. We have developed an photodynamic therapy with topical δ‐aminolevulinic acid (ALA‐PDT) protocol using intense pulsed light (IPL) for treating Bowen’s disease (BD). Three patients diagnosed with BD by skin biopsy were recruited in this study. They received IPL treatment after 3 h of occlusive dressing with application of ALA. This protocol was repeated every 2 weeks for a total of five sessions. The treated areas did not show any signs of BD for more than 1 year; therefore, it appeared that the affected areas showed improvement in all the patients. No patients withdrew from the study because of side‐effects. ALA‐PDT with IPL as a light source is well tolerated by patients and is beneficial for treating BD.     

Eczema molluscatum in tacrolimus treated atopic dermatitis

Eczema molluscatum describes the occurrence of molluscum contagiosum virus infection in a patient with underlying atopic dermatitis. Novel, safe and effective treatment options in atopic dermatitis are the topical immunomodulators tacrolimus and pimecrolimus. One major advantage over corticosteroids is that they do not induce skin atrophy. Some physicians fear that topical immunomodulators may predispose patients to skin infections. We observed a patient with atopic dermatitis who developed eczema molluscatum during treatment with tacrolimus 0.1% ointment. After withdrawal of tacrolimus, the lesions resolved spontaneously over 3 weeks.     

A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo

OBJECTIVE: To assess the safety and efficacy of topical 0.1% tacrolimus vs 0.05% clobetasol propionate. DESIGN: Randomized double-blind trial. SETTING: Department of Dermatology, Hospital Central Dr Ignacio Morones Prieto, San Luis Potosí, México. PARTICIPANTS: From 20 children with vitiligo, 2 symmetrical lesions of about the same size and evolution time were selected. They were devoid of any topical or systemic therapy for 2 months prior to inclusion.Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period. MAIN OUTCOMES MEASURES: The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks. RESULTS: Eighteen (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol presented atrophy, and 2 lesions incurred telangiectasias; tacrolimus caused a burning sensation in 2 lesions. CONCLUSIONS: Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.     

Topical tacrolimus in the treatment of inverse psoriasis in children

Inverse psoriasis is a chronic disease frequently treated with topical corticosteroids. This retrospective case study evaluated the efficacy of tacrolimus 0.1% ointment to treat inverse psoriasis in children. Twelve of 13 patients had complete clearance of their psoriatic lesions within 2 weeks after initiating treatment with topical tacrolimus 0.1%.     

The efficacy of adding topical 5-fluorouracil to micro-needling in the treatment of vitiligo: A randomized controlled trial

Background and Aim

Vitiligo is an autoimmune skin disorder characterized by circumscribed depigmented macules and patches caused by the loss of functional melanocytes. Although there is no definitive treatment for vitiligo, several treatment options have been associated with relative satisfactory outcomes. The purpose of this study was to compare the efficacy of micro-needling in conjunction with topical 5-fluorouracil (5-FU) versus topical tacrolimus ointment in treating vitiligo patches.

Patients and Methods

This study included nineteen participants, each of whom received both treatments on two randomly selected vitiligo patches of approximately the same size and location. On one patch, a combination of weekly micro-needling and topical application of 5-FU solution was used every other day, while on the other, 0.1% tacrolimus topical ointment was applied twice daily. The G-score was used to compare treatment outcomes after 3 months.

Results

The median duration of the disease in our population was 7 years. Six patients (32%) in the micro-needling plus topical 5-FU treated group showed a moderate to excellent response, indicating a significant improvement between both treatments (p-value = 0.019). In contrast, all other patches treated with topical tacrolimus showed poor improvement. Lower extremity and trunk responded more to treatment with micro-needling plus topical 5-FU than upper extremity and acral areas. Moreover, none of those who have had the disease for more than ten years have responded to treatment. Mild erythema, pinpoint bleeding, and irritation were detected only in the micro-needling treated group.

Conclusion

The current study showed that using micro-needling in conjunction with 5-FU could treat vitiligo patients more efficiently than tacrolimus monotherapy. Despite showing moderate to excellent improvement in patches treated with micro-needling and 5-FU, this well-tolerated office-based modality still requires additional research.     

Clinical efficacies of topical agents for the treatment of seborrheic dermatitis of the scalp: A comparative study

Previous studies have shown that topical steroid and shampoo containing zinc pyrithione provide clinical benefits for treatment of scalp seborrheic dermatitis. But the clinical efficacy of topical tacrolimus, a newly developed calcineurin inhibitor on seborrheic dermatitis, is not well investigated yet. We wanted to compare the clinical efficacy of topical tacrolimus with that of conventional treatment (zinc pyrithione shampoo and topical betamethasone) for treatment of seborrheic dermatitis of the scalp. Patients with seborrheic dermatitis of the scalp were randomly allocated to receive topical betamethasone, topical tacrolimus or zinc pyrithione shampoo. Some patients were instructed to continue the treatments for 8 weeks and the others to discontinue the treatments at week 4. We evaluated the efficacy using a clinical severity score, dandruff score and sebum secretion at baseline, week 4 and week 8. All treatment groups showed significant improvements in clinical assessment after 4 weeks. While the patients treated by zinc pyrithione improved continuously even after cessation of the treatment, the patients treated by betamethasone lotion or tacrolimus ointment were aggravated clinically. Topical tacrolimus was as effective as topical betamethasone, and showed more prolonged remission than topical betamethasone. To treat seborrheic dermatitis of the scalp, we think that the combination therapy of topical steroid or topical tacrolimus, and zinc pyrithione is recommended.     

Ausgedehnte aktinische Keratosen Vergleich einer topischen photodynamischen Therapie mit 5-Aminolävulinsäure und topischer 5%iger Imiquimod-Creme

We report on a 75-year-old woman with skin type I suffering for 20 years from multiple actinic keratoses of areas exposed to the sun. The skin of her forearms was treated on one side with imiquimod 5% cream over 4 weeks and on the contralateral side with photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA). Both sides showed good clinical response after 3-months follow-up, suggesting that these modalities can be effectively used for treating widespread multiple actinic keratoses.     

Grover's disease induced by cetuximab

A 71-year-old man exhibited an acute acneiform rash affecting the face and the upper trunk about 2 weeks after starting cetuximab, an epidermal growth factor (EGF) receptor antagonist treatment for metastatic colon cancer. The skin eruption faded after stopping cetuximab and applying topical corticosteroids. The reexposure to cetuximab 3 weeks later provoked a more extended relapse of the skin rash, which then clinically and histologically corresponded to transient acantholytic dermatosis . While the acneiform cutaneous side effects of the EGF receptor antagonists are interpreted as a result of the direct interference with pilosebaceous follicle homeostasis, in this case an acrosyringium-related pathogenesis might be postulated. Applying topical corticosteroids and emollients, the cetuximab therapy could be pursued.     

Intermittent topical corticosteroid/tacrolimus sequential therapy improves lichenification and chronic papules more efficiently than intermittent topical corticosteroid/emollient sequential therapy in patients with atopic dermatitis

Atopic dermatitis (AD) is a common, chronic, relapsing, severely pruritic, eczematous skin disease. Topical steroids are the mainstay of treatment. However, the adverse effects of steroids on hormonal function are the major obstacle for their use as long-term topical therapy. Intermittent dosing with potent topical steroids and/or combination therapy with steroid and tacrolimus have been frequently used in the daily management of AD to overcome the problems accompanying the long term use of steroids. We compared the clinical effects of topical steroid/tacrolimus and steroid/emollient combination treatments in 17 patients with AD. An intermittent topical betamethasone butyrate propionate/tacrolimus sequential therapy improved lichenification and chronic papules of patients with AD more efficiently than an intermittent topical betamethasone butyrate propionate/emollient sequential therapy after four weeks of treatment. Only one out of 17 patients complained of a mild, but temporary, burning sensation after tacrolimus application. The intermittent topical steroid/tacrolimus sequential therapy may be a useful adjunctive treatment for AD.     

308nm准分子激光联合0.1%他克莫司软膏治疗寻常性银屑病疗效观察

目的探讨308nm准分子激光联合0.1%他克莫司软膏治疗寻常性银屑病的临床疗效。方法所有参加研究的患者均接受308nm准分子激光照射2次/w,共6周,且皮损处外搽0.1%他克莫司软膏,早、晚各1次,疗程6周。每2周根据皮损进行治疗前及治疗后的PASI评分比较。结果308nm准分子激光照射平均次数为7.31(5～11)次,外搽0.1%他克莫司软膏平均次数为79.2(69～91)次,治疗6周结束后平均PASI评分为3.15(3.34±1.98),治疗前平均PASI评分为15.31(17.59±3.67),有效率81.40%,治疗前、后2次PASI评分比较,差异有统计学意义(P<0.05)。不良反应轻微,发生率为20.93%。结论308nm准分子激光联合0.1%他克莫司软膏治疗寻常性银屑病疗效好,不良反应少。     

Tacrolimus ointment for the treatment of vulvar lichen sclerosus

The treatment of vulvar lichen sclerosus is generally considered difficult. Ultrapotent corticosteroids represent the most effective topical treatment, but carry the risk of side effects such as skin atrophy. We describe a 71-year-old woman with long-standing vulvar lichen sclerosus refractory to conventional treatment. After 6 consecutive weeks of treatment with tacrolimus ointment 0.1% (Protopic) twice daily, signs and symptoms of lichen sclerosus resolved. To our knowledge, this is the first report of the use of topical tacrolimus, which does not induce skin atrophy, in the treatment of vulvar lichen sclerosus.     

Topical tacrolimus in the treatment of localized scleroderma

Although the cause of localized scleroderma is unknown, an autoimmune mechanism is suspected. We describe two patients with localized scleroderma treated with topical tacrolimus, an immunosuppressive macrolide antibiotic. Topical tacrolimus 0.1% ointment applied twice daily under occlusion led to a significant clinical improvement of late sclerotic lesions and complete clearance of early inflammatory skin lesions in 3 months. These were the first cases of successful topical tacrolimus therapy in localized scleroderma and should be regarded as a promising treatment option for LS, especially on account of its high tolerability that permits prolonged use without side-effects.     

Successful treatment of eosinophilic pustular folliculitis with topical tacrolimus 0.1 percent ointment

Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.