Effect of pimecrolimus on interleukin-33 level in mice with atopic dermatitis and asthma / 中国医师进修杂志

Objective@#To explore the potential mechanism of pimecrolimus in airway remodeling of atopic dermatitis (AD) and asthma mice.@*Methods@#Female BALB/c mice were randomly divided into three groups: control group, atopic dermatitis group and pimecrolimus treatment group. The cell in bronchoalveolar lavage fluid (BALF) was calculated by Ray-Jimsa staining. The structural changes in lung tissue and skin tissue were observed by hematoxylin-eosin (HE) staining, and the level of interleukin (IL)-33, IL-5, IL-13 in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of type 1 collagen (Col1) in the airway of mice were detected by RT-PCR and Western blotting. And western blotting was also used to determine the activation of mitogen-activated protein kinase P38 (P38MAPK) and mitogen-and stress-activated protein kinase 1 (MSK1) in the lungs of mice.@*Results@#Compared with those in the control group, the total number of leukocytes in bronchoalveolar lavage fluid (BALF) and the expression levels of IL-33, IL-13 and IL-5 in serum of atopic dermatitis group were significantly higher, and the difference was statistically significant (P < 0.05). In the atopic dermatitis group, the phosphorylation of P38MAPK and MSK1 protein was increased (1.50 ± 0.43 vs. 0.80 ± 0.43, 1.39 ± 0.08 vs. 0.62 ± 0.08) and the expression of Col1 protein and protein (1 vs. 3.20 ± 0.59, 1.40 ± 0.12 vs. 0.13 ± 0.16) was increased, and the difference was statistically significant (P < 0.05). After pimecrolimus treatment, the number of leukocytes in BALF, the levels of IL-33, IL-5 and IL-13 in serum (213.13 ± 11.89, 657.97 ± 86.47, 143.82 ± 33.02), the phosphorylation of P38MAPK and MSK1 protein in lung tissue (0.10 ± 0.04, 0.85 ± 0.05), and the expression of Col1 mRNA and Col1 protein were decreased (0.61 ± 0.22, 0.48 ± 0.08), and the difference was statistically significant (P < 0.05). The edema of lung and skin tissue and the infiltration of inflammatory cells were alleviated.@*Conclusions@#Pimecrolimus can alleviate the inflammation and airway remodeling in mice by inhibiting the activation of IL-33 related pathways, thereby reducing the incidence of asthma.

Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro

Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 10² nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 10² and 10³ nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 10² nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 10² nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

Comparison of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for the treatment of monobenzone-induced vitiligo-like depigmentation in a mouse model / 中华皮肤科杂志

Objective To compare the therapeutic effect of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for monobenzone-induced vitiligo-like depigmentation in mice.Methods Twentyfive 3-week-old female C57BL/6 mice were randomly and equally divided into 5 groups:negative control group,model group,tea polyphenol group,pimecrolimus group,tacrolimus group.Monobenzone 45％ cream was applied to the back of mice in all the five groups except the negative control group once daily for 40 consecutive days to establish a model of vitiligo-like depigmentation.During the induction of depigmentation,the tea polyphenol group,pimecrolimus group and tacrolimus group were topically treated with tea polyphenol,pimecrolimus and tacrolimus respectively,and the model group remaining untreated.The depigmentation of hairs and skin was observed by naked eyes on a daily basis.Tissue specimens were obtained for histological examination from depigmented skin at nonapplication sites in mice after the end of the experiment.Hematoxylin-eosin staining was conducted to analyze lymphocytic infiltration,reflectance confocal microscopy to observe melanin and melanocytes in skin,and immunofluorescence assay to detect CD8+ T cell infiltration.Results Depigmentation occurred in both application sites and non-application sites of mice in the model group.Compared with the model group,the tacrolimus,pimecrolimus and tea polyphenol groups showed delayed depigmentation,reduced degree and area index of depigmentation,and attenuated lymphocytic infiltration and CD8 + T cell infiltration in depigmented maculae at application sites.In addition,the therapeutic effect of tacrolimus was stronger than that of pimecrolimus and tea polyphenol.Conclusion Tea polyphenol,pimecrolimus and tacrolimus are all effective for the treatment of vitiligolike depigmentation in mice.

A Case of Netherton Syndrome Responsive to 1% Topical Pimecrolimus Cream / 대한피부과학회지

No abstract available.

A Pilot Study of 1% Pimecrolimus Cream for the Treatment of Childhood Segmental Vitiligo

BACKGROUND: There is as yet no effective and safe treatment for vitiligo. One percent pimecrolimus cream, a topical calcineurin inhibitor, has been tried for the treatment of vitiligo, with its therapeutic efficacy having mostly been reported in non-segmental vitiligo. However, questions about the therapeutic efficacy of 1% pimecrolimus cream have remained unanswered regarding segmental vitiligo. OBJECTIVE: The aim of this study was to study the therapeutic efficacy and safety of 1% pimecrolimus cream for segmental childhood vitiligo. METHODS: Nine childhood patients with segmental vitiligo were treated with 1% pimecrolimus cream twice daily for three months, after which good responders were scheduled to continue with the 1% pimecrolimus cream monotherapy. The efficacy and safety of this treatment were determined by the levels of repigmentation, initial response time and the presence of adverse events including burning, dryness, stinging and itching. RESULTS: Four of nine patients achieved mild to moderate responses after three months of treatment and thus continued with treatment. Among these four patients, three achieved an excellent response and one patient achieved a moderate response, with a mean treatment duration of 7.3 months. Transient local burning sensation was the most common adverse event. In comparison with the patients with poor response, those patients with good response showed a shorter disease duration (8.5+/-10.5 mo vs. 13.4+/-10.1 mo), more frequent facial involvement (4/4 patients vs. 3/5 patients) and earlier initial response after treatment (1.0+/-0.0 mo vs. 2.0+/-1.0 mo). CONCLUSION: This study suggests that 1% pimecrolimus cream is an effective and well-tolerated treatment for segmental childhood vitiligo.

A Case of Keratosis Follicularis Squamosa (Dohi) Treated with Topical 1% Pimecrolimus / 대한피부과학회지

Keratosis follicularis squamosa (Dohi) is a keratinizing disorder which is a separate clinical entity from keratosis follicularis (Darier's disease). It occurs predominantly in Japanese and appears clinically as scaly patches of 3~10 mm in diameter with brownish follicular plugs in the center, which are symmetrically scattered on the trunks and thighs. Scales on the margin, slightly detached from the underlying epidermis, look like 'lotus leaves on the water'. The efficacy of minocycline has already been confirmed in many cases. In this report, we describe a case of using 1% of pimecrolimus cream for keratosis follicularis squamosa (Dohi) instead of minocycline.

Successful Treatment of Cutaneous Lesions of Dermatomyositis with Topical Pimecrolimus

Dermatomyositis (DM) is an idiopathic inflammatory process characterized by proximal muscle weakness and cutaneous lesions, such as the Gottron's sign, heliotrope rash, and erythematous photosensitive rash. Administration of systemic agents for the treatment of underlying systemic diseases leads to remission of the cutaneous lesions in many cases. However, cutaneous lesions may remain refractory to treatment. Pimecrolimus is a calcineurin inhibitor with combined anti-inflammatory and immunomodulatory activity. It has high affinity to the skin and low permeation potential, even in patients with acute skin inflammation and in those undergoing post-topical corticosteroid therapy. We herein report two DM patients whose cutaneous lesions were refractory to conventional treatment but showed dramatic response to topical pimecrolimus. The clinical outcomes suggest that topical pimecrolimus may be a good therapeutic alternative for the management of the cutaneous lesions of DM.

Therapeutic Effect of 1% Pimecrolimus for the Treatment of Senile Purpura / 대한피부과학회지

BACKGROUND: Senile purpura is characterized by ecchymoses on the extensor surfaces of the forearms and the dorsa of hands in the elderly. The prevalence is around 10% in the eight and ninth decades. Its occurrence is secondary to the fragility of blood vessel walls caused by atrophy of dermal collagen bundles and solar elastosis due to intrinsic aging and photoaging. For prevention of senile purpura, sunscreens and barrier protection should be used. However, there has been no specific medical treatments developed for senile purpura. OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of a topical calcineurin inhibitor for the treatment of senile purpura. METHODS: Seven patients with senile purpura applied 1% pimecrolimus cream twice daily for 2 weeks. Efficacy was evaluated by the subject's assessment and by the objective findings using photographic assessment. RESULTS: There was an 8.5% reduction in the purpuric area compared with the initial lesion. When the Wilcoxon signed-rank test was used for determination of the purpuric area between the pre-treatment condition and the post-treatment condition, the therapeutic effect was statistically significant (p=0.004). Three of seven patients (42.9%) were satisfied with their treatment, and four of them (57.1%) were neither satisfied nor dissatisfied. No adverse events were observed during the treatment and follow up periods. CONCLUSION: This study shows that 1% pimecrolimus cream can be an effective and safe treatment modality for senile purpura.

Four Cases of Facial Discoid Lupus Erythematosus Successfully Treated with Topical Pimecrolimus or Tacrolimus

Discoid lupus erythematosus (DLE), which is a cutaneous form of lupus erythematosus (LE), is generally refractory to a wide range of topical or systemic therapies. Although the main treatment option for DLE is topical steroids, it is often ineffective or likely to produce long-term side effects. New drugs, including tacrolimus and pimecrolimus, have been developed to overcome the adverse effects of steroids and treat the lesions of DLE for a prolonged period. We herein report 4 cases of facial DLE successfully treated with therapeutic adjuvants, topical tacrolimus or pimecrolimus.

Treatment of Oral Lichen Sclerosus with 1% Pimecrolimus Cream

Lichen sclerosus is a chronic inflammatory mucocutaneous disorder predominately affecting prepubertal girls and postmenopausal women. Isolated lichen sclerosus affecting the oral mucosa is exceedingly rare, and only 13 patients with biopsy-proved isolated oral disease have been reported in the literature. We report on a 7-year-old Korean girl with a well-demarcated 1.2x1.2 cm atrophic white plaque with an erythematous border and focal telangiectasia on the left vermillion lip, extending to the labial mucosa. No other cutaneous surfaces, including genitalia, were involved. An incisional biopsy of the plaque on the lip revealed a patchy lichenoid infiltrate of lymphocytes associated with sclerosis of the papillary dermis and a thinned epidermis consistent with a diagnosis of linear orofacial lichen sclerosus. Treatment with a short course of 1% pimecrolimus cream effectively prevented the progression of this lesion.

The Efficacy of Topical Calcineurin Inhibitors for Treating Lichen Striatus / 대한피부과학회지

BACKGROUND: Lichen striatus is a well-known, acquired, self-healing, linear inflammatory dermatosis. The therapeutic approach that is usually adopted is topical steroid, even though the prolonged use of this may lead to several side-effects, and particularly cutaneous atrophy. OBJECTIVE: The purpose of this study was to evaluate the efficacy of topical calcineurin inhibitors for the treatment of lichen striatus. METHODS: Twenty nine patients received topical application of calcineurin inhibitors twice a day up to the marked disappearance of the cutaneous lesions. RESULTS: Six (20.7%) of 29 patients achieved a complete response after a mean treatment period of 2.5 months. A good response was observed in 8 patients (27.6%) and a partial response was seen in 8 patients (27.6%). Of the 29 patients, 22 patients (75.9%) had more than a 50% response without any severe adverse effects. No significant differences in the therapeutic responses were found with regard to the patients' ages, the duration of the disease and the length of the treatment periods. CONCLUSION: Our results show that topical calcineurin inhibitors may well represent a useful therapeutic alternative for the treatment of lichen striatus.

Combination of 308 nm excimer laser with topical pimecrolimus cream for vitiligo in childhood / 中华皮肤科杂志

Objective To assess the efficacy and safety of 308 nm excimer laser plus topical pimeevaluated after 15 and 30 times of laser therapy respectively.ResultsExcept for one patient,all patients were able to be evaluated for effiicacy.After 30 times of laser therapy,the response and excellent response rates were 89.6%and 77.1%respectively,in group A，5.0%and 52.1%respectively in group B;both rates were significantly higher in group A than in group B(both P＜0.05).Also,a highler repigmentation rate was obtained in facial lesions in group A compared with group B.Conclusions The 308 nm excimer laser is safe,erective and well-tolerated for vitiligo in childhood,and the combination with topical imecrolimus cream may improve its efficacy in facial vitiligo.

Multicenter Survey of the Efficacy and Compliance with UsingTopical Pimecrolimus by Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that's influenced by many genetic and environmental factors. Various treatment modalities are being applied for AD, including phototherapy, topical applicants and systemic agents. However, there has been no mass survey in Korea concerning the compliance of patients' to use their prescribed medication, which might influence the clinical efficacy of the physicians' treatment. OBJECTIVE: The purpose of the present study is to evaluate the efficacy, safety and patient compliance with using topical pimecrolimus to treat AD. METHODS: We reviewed the medical recordings, laboratory profiles, clinical severity scoring and photographs of AD patients at 9 general hospitals in Seoul and the local area of Korea. Interviews with the patients and a telephone survey were also done. Those patients who weren't perscribed topical applicants or those who did not use topical pimecrolimus or steroid within 6 months were excluded from this study. RESULTS: Topical pimecrolimus cream effectively controlled AD with a reduction of the EASI score from baseline 13.75 to 11.39 at 2 weeks and 4.46 at 10 weeks of topical pimecrolimus application. When topical pimecrolimus cream was applied for more than 12 months it significantly suppressed the recurrence and reactivation of AD (p<0.05). Although 22.6% of the patients complained of adverse effects, these were all transient and they did not evoke significant medical problems. Using topical pimecrolimus cream did not show significant adverse effects or complications. CONCLUSION: Topical pimecrolimus might well be an effective treatment modality for treating AD when patients show good compliance for applying the cream.

Multicenter Survey of the Efficacy and Compliance with UsingTopical Pimecrolimus by Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that's influenced by many genetic and environmental factors. Various treatment modalities are being applied for AD, including phototherapy, topical applicants and systemic agents. However, there has been no mass survey in Korea concerning the compliance of patients' to use their prescribed medication, which might influence the clinical efficacy of the physicians' treatment. OBJECTIVE: The purpose of the present study is to evaluate the efficacy, safety and patient compliance with using topical pimecrolimus to treat AD. METHODS: We reviewed the medical recordings, laboratory profiles, clinical severity scoring and photographs of AD patients at 9 general hospitals in Seoul and the local area of Korea. Interviews with the patients and a telephone survey were also done. Those patients who weren't perscribed topical applicants or those who did not use topical pimecrolimus or steroid within 6 months were excluded from this study. RESULTS: Topical pimecrolimus cream effectively controlled AD with a reduction of the EASI score from baseline 13.75 to 11.39 at 2 weeks and 4.46 at 10 weeks of topical pimecrolimus application. When topical pimecrolimus cream was applied for more than 12 months it significantly suppressed the recurrence and reactivation of AD (p<0.05). Although 22.6% of the patients complained of adverse effects, these were all transient and they did not evoke significant medical problems. Using topical pimecrolimus cream did not show significant adverse effects or complications. CONCLUSION: Topical pimecrolimus might well be an effective treatment modality for treating AD when patients show good compliance for applying the cream.

A Case of Plasma Cell Cheilitis Treated with Topical Pimecrolimus / 대한피부과학회지

Plasma cell cheilitis is a rare, idiopathic, benign inflammatory disease of lips, characterized by dense plasma cell infiltrates in the upper dermis. It presents as erythematous patches with erosion usually on the lower lip of elderly people. Although, various therapeutic options, including topical steroids, intralesional injection of glucocorticoids, oral nystatin and topical antibiotics have been tried, none of them is promising. A 68-year-old woman presented with a 4-month history of erosive patches with crusts on her lower lip, which was resistant to topical corticosteroids. A histopathologic examination revealed dense inflammatory cell infiltration mainly consisting of plasma cells in the dermis, consistent with plasma cell cheilitis. She was treated with topical pimecrolimus and after 2 weeks of application, the lesion started to get better. After 7 weeks it had almost disappeared. Herein, we present a case of plasma cell cheilitis treated with topical application of pimecrolimus.

Treatment of Facial Seborrheic Dermatitis with Pimecrolimus Cream 1%: An Open-Label Clinical Study in Korean Patients

Pimecrolimus cream 1% has shown to be effective in patients with a variety of inflammatory cutaneous disorders. And it might be a useful modality in the treatment of seborrheic dermatitis. This prospective study was aimed at assessing the efficacy and tolerability of pimecrolimus cream 1% in the treatment of facial seborrheic dermatitis. Twenty patients were instructed to apply pimecrolimus cream 1% for 4 consecutive weeks. Assessment of the disease severity was performed at baseline and at week 1, 2, and 4. Clinical assessments of erythema, scaling, and pruritus were measured using a 4-point scale (0-3). Global assessments of the disease severity by patients and investigators were performed at each visit. Mean clinical scores of erythema, scaling, and pruritus significantly improved by 87.4%, 91.9%, and 91.5% respectively at week 4 (p<0.001). Improvements in the global assessment of disease severity determined by patients and investigators also showed excellent results. No specific adverse events other than transient burning and tingling sensations were noted. The relapse of facial seborrheic dermatitis was mostly observed between 3 to 8 weeks after the discontinuation of pimecrolimus. We suggest that the topical application of pimecrolimus cream 1% can be an effective and safe alternative for treatment of facial seborrheic dermatitis.

Lichen Striatus in a Girl: Successful Treatment with Pimecrolimus

Lichen striatus (LS) is a self-resolving condition, which may occasionally need treatment for significant pruritus, a persistent course or cosmetic problems. The options for treatment have usually been topical or intralesional corticosteroids, salicylic acid, coal tar, or more recently, topical tacrolimus and pimecrolimus. We report a case of LS successfully treated with pimecrolimus in a 15-year-old girl.

A Case of Generalized Lichen Planus Treated with Topical Pimecrolimus / 대한피부과학회지

Lichen planus is a chronic papulosquamous disease chracterized by various clinical manifestations of the skin and mucous membrane. Although its etiology is not fully understood, lichen planus has been associated with viral infection, autoimmune disease, psychologic factors, and medications. Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of lichen planus. The former includes antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8+ cytotoxic T cells, the latter includes mast cell degranulation and matrix metalloproteinase activation. A large variety of topical and systemic therapies are available for the treatment of lichen planus. Also, topical pimecrolimus (Elidel(R) 0.1% cream) may be used because of its inhibitory effect on activated T cells and mast cell degranulation. Recently, it has been shown to be effective in the treatment of oral and genital lichen planus. But, its effect in cutaneous lichen planus has not been reported to date. We report on the successful use of topical pimecrolimus in the management of a generalized lichen planus patient.

A Case of Tinea Incognito Induced by 1% Pimecrolimus (Elidel(R)) Cream / 대한피부과학회지

Tacrolimus and pimecrolimus represent a new class of topical non-steroidal medication currently used in the treatment of a variety of inflammatory skin lesions. We report a case of a patient in whom topical pimecrolimus therapy resulted in tinea incognito. Mycologic examination, including a KOH smear and fungal culture, was positive for hyphae and colonies of trichophyton mentagrophytes. The lesion was treated with oral griseofulvin and topical clotrimazole.

Tratamento de balanopostite com pimecrolimus creme a 1% / The treatment of balanitis with pimecrolimus cream 1%

Balanopostite é o processo inflamatório que acomete glande e prepúcio, caracterizando-se por eritema, edema, "rash", prurido, disúria, sangramento, erosão, ulceração da glande e presença de exsudato subprepucial. Apresentamos um caso de balanopostite tratado com pimecrolimus creme a 1% após terapia convencional sem sucesso.