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.     

Spotlight on Topical Pimecrolimus in Pediatric Atopic Dermatitis

Topical pimecrolimus 1% cream (Elidel®) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1–2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.     

Topical use of pimecrolimus in atopic dermatitis: Update on the safety and efficacy

Pimecrolimus has been approved for more than five years for the treatment of atopic dermatitis in Germany. An important difference in the safety profile of this drug compared with topical corticosteroids is the lack of potential side effects which are often observed upon prolonged use of topical corticosteroids (skin atrophy, steroid‐induced rosacea or perioral dermatitis). Even after prolonged use in sensitive skin areas, no tolerance to this drug is induced, in contrast to that seen with topical corticosteroids. The most common side effect of pimecrolimus is burning. Placebo‐controlled studies suggest that pimecrolimus is associated with a slightly increased incidence of herpes simplex infections. Compared with topical corticosteroids, pimecrolimus does not increase the overall incidence of skin infections (including recurrent herpes simplex infections). So far, clinical studies with pimecrolimus have not shown any evidence of an increased risk of malignancy. The analysis of spontaneously reported adverse events has also not shown any evidence of malignancy caused by pimecrolimus. This corresponds with the results of a case‐control study from a large U.S. database. According to the German guidelines on atopic dermatitis, topical calcineurin inhibitors are indicated when topical corticosteroids are not indicated or when an anticipated lengthy treatment course would lead to inevitable side effects. On sensitive areas such as face, intertriginous regions and scalp, they are preferred as first‐line choice over topical corticosteroids.     

Spotlight on topical pimecrolimus in atopic dermatitis

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.     

Pimecrolimus

Pimecrolimus (Elidel) is a topically active, nonsteroid, calcineurin inhibitor that has shown efficacy in controlling symptoms of atopic dermatitis in adult and pediatric patients. Topical pimecrolimus 1% cream is approved in the US for the short-term and intermittent long-term treatment of mild-to-moderate atopic dermatitis in non-immunocompromised patients aged >/=2 years who do not respond well to, or may have adverse effects with, conventional treatments. Pimecrolimus 1% cream is an effective and well tolerated treatment for atopic dermatitis in infants, children, adolescents, and adults. Pimecrolimus is effective at reducing the incidence of disease flares and, thus, the need for rescue treatment with topical corticosteroids. The drug also improves the health-related quality of life (HR-QOL) of children and adolescents, and improves the QOL of parents of children with atopic dermatitis. Furthermore, pimecrolimus does not cause skin atrophy, a problem commonly associated with topical corticosteroids, and is not associated with clinically relevant systemic adverse events. Thus, topical pimecrolimus 1% cream is an effective treatment option for the management of mild-to-moderate atopic dermatitis.     

吡美莫司治疗湿疹皮炎类皮肤病的进展

吡美莫司是一类新型局部免疫抑制剂,主要用于特应性皮炎的治疗.近年来该药的应用范围有所扩大,可被广泛应用于多种湿疹皮炎类皮肤病,如特应性皮炎、湿疹、接触性皮炎、口周皮炎等.多项临床研究均表明,每天2次外用吡美莫司可达到良好的疗效,且不良反应小,提示该药在治疗湿疹皮炎类疾病中有着广阔的应用前景.

Abstract：

As a new type of topical immunosuppressive agent,pimecrolimus is mainly used in the treatment of atopic dermatitis.Recently,the application range of pimecrolimus has been broadened and it has been widely used in many allergic dermatoses,such as atopic dermatitis,eczema,contact dermatitis,perioral dermatitis,et al.Several clinical studies have suggested that topical pimecrolimus twice daily has favorable effect with few side effects.Therefore,pimecrolimus may have a promising future in the treatment of allergic dermatoses such as dermatitis and eczema.     

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.     

Clinical remission of disseminated molluscum contagiosum infection in a patient with atopic dermatitis treated with dupilumab

Atopic dermatitis predisposes to skin infections, and on the other hand, some therapies used for atopic dermatitis may worsen viral infections whose lesions may be more diffuse and resistant to treatment. The authors present a patient with severe atopic dermatitis and disseminated molluscum contagiosum infection. The molluscum contagiosum did not clear with topical treatment, and it worsened her atopic dermatitis even more, so the authors started treatment with dupilumab. After two months, the patient's dermatitis went into clinical remission and there was resolution of the infection with no recurrence at the 12-month follow-up. Dupilumab is nowadays a promising treatment for severe atopic dermatitis. To our knowledge, only four reports of molluscum contagiosum during dupilumab therapy have been reported in the literature, with contrasting effects. According to the authors’ experience, treatment with dupilumab appears to be a safe alternative for patients with severe atopic dermatitis who are also infected with molluscum contagiosum, as opposed to other treatments such as systemic corticosteroids or cyclosporine.     

Use of pimecrolimus cream in disorders other than atopic dermatitis

BACKGROUND: Pimecrolimus is indicated for treatment of atopic dermatitis and has been evaluated in many other disorders. OBJECTIVE: To review the efficacy of pimecrolimus in treatment of disorders other than atopic dermatitis. METHODS: We performed a PubMed search of the English-language literature using the key word "pimecrolimus." We reviewed articles reporting the use of pimecrolimus in disorders other than atopic dermatitis and classified them by the type of study used to evaluate efficacy. RESULTS: Randomized, double-blind studies have shown that pimecrolimus is superior to vehicle in treatment of seborrheic dermatitis, hand dermatitis, and asteatotic eczema but have yielded conflicting results regarding intertriginous psoriasis and vitiligo. Open-label studies involving four or more patients have shown favorable results in many disorders, including contact dermatitis, rosacea, lichen sclerosus, and oral and genital lichen planus. Case reports have shown that topical pimecrolimus may be useful in cutaneous graft-versus-host disease, lichen striatus, cutaneous lichen planus, and many other disorders. CONCLUSIONS: Topical pimecrolimus appears to be an effective treatment for many disorders other than atopic dermatitis, especially seborrheic dermatitis, hand dermatitis, and asteatoic eczema. It may be effective in many other disorders, but its role in these disorders remains to be clarified by additional studies.     

Efficacy and Economics of Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that frequently affects infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5-20% of the pediatric population. Studies have shown that atopic dermatitis is associated with considerable economic costs and decreased quality of life. There is no proven curative therapy at present for atopic dermatitis; first-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as appropriate. Topical corticosteroids, while effective in many patients, carry the concern of local and systemic adverse effects. As a result, physicians and patients are reluctant to utilize stronger topical corticosteroids in certain areas of the body and for prolonged periods of time. The purpose of this article is to review the efficacy and economics of topical calcineurin inhibitors in the treatment of atopic dermatitis. This new class of agents (specifically tacrolimus ointment and pimecrolimus cream) represents an exciting advance in the treatment of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are effective and do not cause the adverse effects associated with topical corticosteroids. Several studies have provided evidence that topical calcineurin inhibitors positively affect the quality of life of patients and their caregivers. Compared with branded topical corticosteroids and previous standards of care, topical calcineurin inhibitors appear to be a cost-effective treatment option. Drawing comparisons between tacrolimus and pimecrolimus is difficult because definitive head-to-head comparative studies involving these drugs have not been conducted.     

Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrhoeic dermatitis. A randomized open-label clinical trial

BACKGROUND: Seborrhoeic dermatitis is a chronic inflammatory disease with remissions and exacerbations, characterized by erythema, scaling and pruritus primarily on the face, scalp and chest. Corticosteroids and antifungals are the mainstay of therapy. However, chronic use of corticosteroids is associated with side-effects such as skin atrophy and telangiectasia. Pimecrolimus, an inhibitor of calcineurin, has been used successfully in one patient with seborrhoeic dermatitis. OBJECTIVES: The objective of this randomized open-label clinical trial was to compare the efficacy and tolerability of pimecrolimus in comparison with a potent corticosteroid (betamethasone 17-valerate) in the treatment of seborrhoeic dermatitis. METHODS: Twenty patients with seborrhoeic dermatitis were included in this study, 11 patients in the pimecrolimus 1% cream group and nine patients in the betamethasone 17-valerate 0.1% cream group. Patients were instructed to use a thin layer of the study products twice daily at the lesional area and to discontinue treatment as soon as symptoms were absent. Clinical measures assessed were erythema, scaling and pruritus which were evaluated using a four-point scale (0-3). RESULTS: Both pimecrolimus and betamethasone were highly effective in the treatment of seborrhoeic dermatitis. Betamethasone reduced all three parameters, erythema, scaling and pruritus, faster than pimecrolimus, but the differences in reduction were not statistically significant. Relapses were observed more frequently and were more severe with betamethasone than with pimecrolimus. Moreover, pruritus was not observed after discontinuation of treatment from day 15 and beyond in the pimecrolimus group, whereas it was reported in most patients of the betamethasone group. This difference was statistically significant. CONCLUSIONS: It appears that pimecrolimus, a nonsteroidal topical treatment, may be an excellent alternative therapeutic modality for treating seborrhoeic dermatitis.     

Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis

BACKGROUND: Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine release developed specifically for the treatment of inflammatory skin diseases. AIM: The objective of this study was to evaluate blood concentrations and tolerability of pimecrolimus during topical treatment. METHODS: Twelve adult patients with extensive atopic dermatitis were enrolled in an open-label, noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3 weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood concentrations were measured at regular time points, and the safety and tolerability were monitored throughout the study. RESULTS: In 78% of the 444 blood samples evaluated, pimecrolimus concentrations remained below the limit of quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There was no indication of drug accumulation. Pimecrolimus was well tolerated locally and systemically. CONCLUSION: The 3-week twice daily treatment with pimecrolimus cream 1% results in consistently low pimecrolimus blood concentrations with no accumulation. Pimecrolimus cream appears suitable for the long-term management of atopic dermatitis.     

Pimecrolimus 1% cream (Elidel) for atopic dermatitis

Pimecrolimus is an immunomodulating medication that inhibits production of inflammatory cytokines in the skin and this compound was specifically developed for the treatment of inflammatory skin diseases. Phase II and III clinical trials with the topical formulation of pimecrolimus (Elidel cream, Novartis) have shown that it is safe and effective for use in patients with atopic dermatitis (AD). The US FDA recently approved Elidel for use in patients >or=2 years of age and older with mild to moderate atopic dermatitis (AD).     

Topical noncorticosteroid immunomodulation in the treatment of atopic dermatitis

At present, the first-line drugs for treating atopic dermatitis are topical corticosteroids. They are effective when used short-term; however, long-term use of the corticosteroids is associated with suppressive effects on the connective tissue, seen as skin atrophy or resistance to therapy. Currently, two topical noncorticosteroid immunomodulators tacrolimus (FK506) and pimecrolimus (SDZ ASM 981) are under development, or already on the market in some countries for atopic dermatitis. These two compounds show structural similarity. In T lymphocytes they bind to the same cellular receptor, the FK-binding protein (FKBP) or macrophilin-12. Tacrolimus shows a 3-fold greater affinity to FKBP compared with pimecrolimus. The tacrolimus/ pimecrolimus-FKBP complex further binds to calcineurin, an enzyme vital for the early activation of T cells. The consequence of calcineurin binding is a lack of activation of both T helper cell types 1 and 2. Further effects of these compounds have been suggested on other inflammatory cells, such as Langerhans cells and mast cells/basophils. In contrast to corticosteroids, no suppressive effects on connective tissue cells have been observed. Taken together, treatment of inflammation results in healing of the barrier function of the skin. This again results in reduced bioavailability of the drug, as compared with systemic use. Placebo-controlled studies have shown the efficacy of both tacrolimus (at 0.03 and 0.1%) and pimecrolimus (at 0.6 and 1%). The main adverse event in these studies has been a burning sensation and increased pruritus at the site of application. Typically, these adverse events are observed only during the first days of treatment. Long-term safety studies, of up to one year, have not revealed any new adverse events. So far, long-term use of topical noncorticosteroid compounds has not been associated with signs of immune deficiency. Although there is currently no evidence for clinically relevant, prolonged adverse effects, some of these, such as an increased risk of photocarcinogenesis, need to be monitored. There is evidence from tacrolimus studies that monotherapy results in better long-term results when compared with combination therapy with corticosteroids. Tacrolimus and pimecrolimus could replace topical corticosteroids as the first-line treatment of atopic dermatitis.     

Nicolau Syndrome Following Etanercept Administration

Background: Treatment options for seborrheic dermatitis are numerous, including both topical and systemic agents (e.g. topical corticosteroids, oral antifungals, and psoralen plus UVA). However, long-term use of topical corticosteroids may lead to adverse effects. Pimecrolimus 1% cream is an effective and well tolerated treatment for seborrheic dermatitis. Objective: To explore the efficacy of pimecrolimus 1% cream for the treatment of seborrheic dermatitis lesions resistant to conventional treatments. Methods: Sixteen patients with resistant seborrheic dermatitis of the face applied pimecrolimus 1% cream twice daily for 2 weeks. The lesions were assessed clinically and the severity of the signs were assessed using a 4-point score. Additionally, the scores of all affected regions (paranasal, forehead, and eyebrows) were evaluated separately to assess whether different results would be obtained in different regions of the face. Also, patients completed self-assessments on a 100 mm Visual Analogue Scale (VAS) at each visit. Results: Statistically significant reductions in the scores of all parameters were observed at day 7 and day 14 of the study. There were no significant differences between the responses on the three regions of the face. No adverse effects were reported except for temporary pruritus immediately after the application of pimecrolimus 1% cream in one patient. Conclusion: Although the interpretation of efficacy was limited by the open-label, non-controlled study design and the small number of patients, this trial suggests that pimecrolimus 1% cream may be a successful treatment choice for patients with resistant seborrheic dermatitis of the face.     

The direct cellular target of topically applied pimecrolimus may not be infiltrating lymphocytes

Summary Background Topically applied calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis. When systemically administered, these agents cause immunosuppression via inhibition of calcineurin in lymphocytes. As topical agents, the mechanism of action is poorly defined. Objectives To test the hypothesis that skin‐infiltrating lymphocytes are directly targeted when calcineurin inhibitors are applied to the skin. Methods Ten patients with atopic dermatitis were treated with 1% pimecrolimus cream twice daily to target lesions. Skin biopsies were performed before and 48 h after beginning therapy. We assessed the cellular localization of NFAT1 and NFAT2 as a surrogate measure of intracellular calcineurin activity (e.g. increasing cytoplasmic localization with increasing calcineurin inhibition). Results All patients showed a clinical response, at both 48 h and 2 weeks. As previously described, NFAT2 localized to the follicular keratinocytes, and its activation was partially inhibited by topical pimecrolimus. NFAT1 was found to be expressed by follicular and interfollicular keratinocytes, and its mostly nuclear localization was not affected by topical pimecrolimus therapy. Both NFAT1 and NFAT2 were found in the infiltrating lymphocytes. However, using both manual counting as well as an automated method to assess nuclear intensity of NFAT staining, we found that the proportion of infiltrating leucocytes with nuclear (‘activated’) NFAT did not change following therapy with pimecrolimus. Conclusions Our results suggest that topical pimecrolimus does not act primarily by inhibiting the calcineurin/NFAT axis in lymphocytes but may instead act by other mechanisms, possibly by decreasing NFAT2 activity in follicular keratinocytes.     

Molluscum contagiosum in atopic dermatitis treated with 0.1% tacrolimus ointment

A case of molluscum contagiosum arising on the face and neck of a woman using topical tacrolimus over a period of 6 weeks for the treatment of atopic dermatitis is presented. Of particular note, these lesions remained confined to areas treated with tacrolimus and did not extend to adjacent regions treated with topical corticosteroids.     

外用吡美莫司治疗18岁以下特应性皮炎患者的Meta分析

目的 评价外用吡美莫司治疗儿童-婴儿特应性皮炎的疗效和安全性。方法 计算机检索Cochrane图书馆（2010年第2期）、Medline（1966～2010）、Embase（1974～2010）和CBM（1978～2010.6）、CNKI（1980～2010.6）等数据库,纳入所有外用吡美莫司与安慰剂或外用糖皮质激素或外用他克莫司的随机对照试验,由2组研究者（每组3人）独立提取资料与评价质量,用RevMan5.0软件统计分析。结果 共纳入16个研究,5076例儿科患者,均为高质量研究。Meta分析治疗有效率,结果显示：1%吡美莫司无论短期疗程和长期疗程均优于安慰剂（P值均小于0.01）,1%吡美莫司与0.03%他克莫司比较疗效无差别（P值均大于0.05）,但不如0.1%他克莫司有效（P=0.01）。所有研究均未发现严重的不良反应。最常见的不良反应是皮肤刺激和烧灼感。结论 外用吡美莫司治疗儿童-婴儿特应性皮炎有效安全,能改善IGA评分、瘙痒评分及PIQoL-AD评分。尚不清楚与TCs的疗效相比有无优势,故需进行更多的RCT。