A 14-year-old girl with lichenoid sarcoidosis successfully treated with tacrolimus

We report a case of lichenoid sarcoidosis in a young girl treated by oral tacrolimus and methylprednisolone. The patient had had a skin eruption from 1 year of age and had developed uveitis at 2 years of age. Her sight had become affected by the uveitis at 8 years of age. When she was 14, she was admitted to the ophthalmology department of our hospital to start treatment with tacrolimus (FK506). She was referred to the department of dermatology for her skin lesions, which were flat, pinkish or normal skin-colored papules scattered on her extremities and the backs of her hands. Upon histology, epithelioid granulomas were seen in the upper dermis and around the erector pili muscles. She received tacrolimus (FK506) 6 mg/day for 3 months for her uveitis. The eye lesions subsided somewhat, and the skin lesions were almost healed after the 3-month course of tacrolimus. However, 4 months after stopping the tacrolimus, her skin and eye lesions relapsed. At that point, she was started on methylprednisolone 16 mg/day for her uveitis. With the methylprednisolone treatment, the inflammation of the eye lesion immediately healed, as did the skin lesions.     

A Case of Generalized Lichen Sclerosus et Atrophicus

A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow-band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient.     

0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observer-blinded study

The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.     

透明质酸凝胶与他克莫司软膏治疗面部脂溢性皮炎疗效观察

目的分别探讨透明质酸凝胶和他克莫司软膏治疗面部脂溢性皮炎的疗效、安全性和对皮肤屏障功能的影响。方法 89例面部脂溢性皮炎患者随机分为试验组和对照组。试验组外用透明质酸凝胶,对照组外用他克莫司软膏,在0、7、14、28 d进行随访,每次随访用VISIA皮肤图像分析仪观察面部红色区,评估患者病情,并测定皮肤屏障功能相关指标。结果疗程结束后,试验组和对照组显效率分别为82.2%和86.4%,差异无统计学意义(P0.05);试验组和对照组角质层含水量分别为(56.60±9.54)和(55.14±11.57),两组差异无统计学意义(P=0.610);试验组和对照组经表皮水分丢失值分别为[(19.37±5.18)g/(m~2·h)]、[(25.10±14.0)g/(m~2·h)],两组差异无统计学意义(P=0.142)。结论透明质酸凝胶治疗面部脂溢性皮炎疗效与他克莫司软膏同样有效,透明质酸凝胶能改善皮肤屏障功能,减轻皮损,使用安全,耐受性好,值得临床推广。     

Fluconazole in the treatment of tinea versicolor

Patients with tinea versicolor (TV, n = 603) aged 18–65 years entered into an open, randomized, multicenter study to investigate the efficacy and toleration of three dosage regimens of fluconazole. The study was conducted in 10 different centers in six cities in Egypt.
The patients were randomly assigned to one of three groups:
Group I: received single 150 mg fluconazole capsule repeated weekly for 4 weeks;
Group II: received two 150 mg capsules of fluconazole in a single dose repeated weekly for 4 weeks;
Group III: received two 150 mg capsules of fluconazole in a single dose that could be repeated 2 weeks later.
Five visits were scheduled for each group and the last follow-up visit was always 28 days after the last fluconazole dose. Response to treatment was assessed clinically and by microscopic examination of KOH mounts of skin scrapings, weekly and 28 days after the last fluconazole dose. The number of fluconazole doses administered was guided by clinical and mycologic response, and the dose was repeated only if the patient showed residual clinical lesions or positive microscopy for skin scrapings.
Final evaluation was rated as cure (disappearance of lesions with no or slight color changes), improvement (no scales while color changes were much less but still obvious), and failure (no or slight changes from baseline). Mycologic assessment was rated as eradication, persistence or relapse. All adverse events were recorded during the treatment period.     

Successful treatment of acrodermatitis continua of Hallopeau with sequential combination of calcipotriol and tacrolimus ointments

Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis affecting the digits. We report on a 43-year-old female patient who had been suffering from ACH for more than 20 years. Despite the fact that the disease was localized on one finger during the whole period, several topical and systemic treatments resulted in only temporary or partial improvement of the lesion. Although the monotherapies with calcipotriol and tacrolimus ointments gave no satisfying results in the long-term management of the disease, the combination of both agents led to a continuous improvement of the patient's skin condition.     

Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis

Background  Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin.
Objectives  To assess the distribution of tacrolimus in the skin and the systemic pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment.
Methods  We investigated skin distribution of topically applied tacrolimus and systemic pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0·1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples.
Results  Of 14 patients, 11 completed treatment and were analysed. Mean ± SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 ± 20 and 595 ± 98 ng cm⁻³, respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0·025 ng mL⁻¹) and 94% below 1 ng mL⁻¹. Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians' assessments showed that tacrolimus ointment was effective and well tolerated.
Conclusions  Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.     

Topical FK506 (tacrolimus) therapy for facial erythematous lesions of cutaneous lupus erythematosus and dermatomyositis.

Tacrolimus is a prototype of a class of topical immunosuppressive agents with great potential for the treatment of inflammatory skin diseases. Topical tacrolimus therapy was applied to facial skin lesions in 11 cases of cutaneous lupus erythematosus (LE) and dermatomyositis. Of the 11 patients, 6 (3 systemic LE, one discoid LE and 2 dermatomyositis) showed a marked regression of their skin lesions after tacrolimus therapy, but 4 patients (3 discoid LE and one dermatomyositis) were resistant to the therapy. A good response was observed for facial erythematous lesions with edematous or telangiectatic changes in systemic LE and dermatomyositis. In discoid LE with typical discoid lesions, tacrolimus brought no improvement. Topical tacrolimus will become a new tool for managing the skin lesions of collagen diseases.     

Mouth ulcers in patients receiving tacrolimus

INTRODUCTION: The buccal side effects of immunodepressors are well defined with cyclosporine and certain antimitotic agents. We report a case of buccal ulcerations in a patient treated with a new immunosuppressive macrolide: tacrolimus (Prograf). OBSERVATION: A 53 year-old woman presenting a severe cardio-myopathy, underwent heart transplantation in May 1997. Tacrolimus was introduced in October 1997 after 3 episodes of acute reject. Eight months after tacrolimus, painful apthoid buccal ulcerations appeared. Biopsy of the buccal mucosa and other biological examinations revealed no particular etiology. Since tacrolimus could not be stopped, treatment with thalidomide was initiated. It was suspended on two occasions due to adverse events. The buccal ulcerations relapsed rapidly. The intrinsic imputability of tacrolimus in the occurrence of these lesions was noted "l2" ("plausible"). DISCUSSION: Several arguments suggest that these buccal ulcerations may result from the toxicity of tacrolimus: 1) absence of past history of apthae; 2) anatomo-clinical aspect of the lesion differing from that of common apthae, but similar to the ulcerations observed with nicorandil; 3) delay in occurrence of analogous ulcerations compared with that observed with methotrexate or nicorandil; 4) absence of another etiology; 5) relapse of ulcerations on two occasions after suspension of thalidomide, whilst tacrolimus was continued.     

Topische Anwendung von Tacrolimus bei Necrobiosis lipoidica

Necrobiosis lipoidica (NL) is a chronic inflammatory skin disease that is difficult to treat. The etiology is unknown, but vascular abnormalities and immunologic factors have been implicated. We treated a patient with long-standing NL with multiple vascular risk factors (diabetes mellitus, protein S-deficiency, and antiphospholipid syndrome) with topical tacrolimus, a non-steroidal immunomodulator that causes no skin atrophy. After 12 weeks of topical tacrolimus (0.1%) ointment, our patient already showed a good remission with a significant decrease in inflammatory signs.     

他克莫司软膏对银屑病皮损角质形成细胞增殖分化的影响

目的探讨他克莫司软膏对银屑病皮损处角质形成细胞增殖分化的影响。方法采用免疫组化的方法检测10例0.1%他克莫司软膏治疗前后寻常性银屑病(斑块型)患者的皮损组织及10例正常健康人的皮肤组织中Ki-67,CK10的水平,并进行比较。结果 0.1%他克莫司软膏治疗后银屑病皮损的表皮Ki-67的水平明显升高,CK10的水平明显降低,差异均有统计学意义(P均<0.05)。结论他克莫司软膏对银屑病皮损处角质形成细胞分化有显著的抑制作用,对角质形成细胞增殖有促进作用。     

Subcutaneous mycosis due to Scopulariopsis brevicaulis in an immunocompromised patient

BACKGROUND: Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus.CASE REPORT: A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent.DISCUSSION: This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.     

Tinea capitis profunda due to Trichophyton verrucosum with cMRSA superinfection in an infant

A 28-month-old boy developed a cutaneous and subcutaneous lesion of the scalp together with alopecia. Treatment with sulfadiazine silver ointment and oral administration of cefaclor failed. The boy lived on a farm where cows and calves were present. He presented with a 5 cm erythematous, erosive, edematous, and sharply defined lesion with yellow crusts and circumscribed alopecia on the temporoparietal scalp. Peripheral hairs were easily epilated. Swabs from the wound revealed cMRSA (community acquired methicillin-resistant Staphylococcus aureus, Panton Valentine Leukocidin [PVL] toxin negative). There was no improvement after treatment with cefuroxime intravenously over 3 days. Therapy was changed to vancomycin and fosfomycin. Because of the purulent abscess, surgical incision was performed. PCR (polymerase chain reaction)-Elisa assay detected Trichophyton (T.) interdigitale-DNA from wound secretion and skin biopsy. Because of the clinical and molecular diagnosis of tinea capitis, oral antifungal therapy with fluconazole 5 mg kg(-1) body weight was started, along with cotrimoxazole and fosfomycin for the cMRSA. After 4 weeks incubation, the causative agent T. verrucosum was grown on culture and its identity confirmed by sequencing of the "internal transcribed spacer" (ITS) region of the ribosomal DNA. After 4 weeks of fluconazole, the lesion was nearly healed.     

A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis

BACKGROUND: Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects. OBJECTIVES: In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD. METHODS: Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3. RESULTS: By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group. CONCLUSIONS: Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.     

Disseminated cutaneous cryptococcosis in an immunocompetent elderly long-term pigeon fancier

Cutaneous cryptococcosis is classified as localized cutaneous cryptococcosis and cutaneous manifestations of disseminated cryptococcosis. The former presents as lesions, confined to isolated parts of the skin, which are neither systemically disseminated nor associated with cryptococcal fungemia or antigenemia. The latter presents as lesions through dissemination of Cryptococcus from visceral organs such as the lungs, with most cases being immunosuppressed hosts. We report the case of an immunocompetent elderly long-term pigeon fancier who presented with disseminated cutaneous cryptococcosis caused by Cryptococcus neoformans. Although the patient had been at risk of inhaling the pathogen by keeping pigeons for many years, and had been treated with topical steroids for a localized nodular lesion, the cause of development of multiple skin lesions could not be determined. The patient paradoxically showed no pulmonary or central nervous system symptoms, fungemia or glucuronoxylomannan antigenemia. Treatment with oral itraconazole 200 mg/day was not effective, but combination therapy of 5-fluorocytosine 200 mg/kg per day and fluconazole 100 mg/day resolved the disease.     

Topical tacrolimus for the treatment of lichen simplex chronicus

Owing to severe itching and scratching, the natural course of lichen simplex chronicus (LSC) is clinically characterized by typical lichenoid lesions. Topical corticosteroids are often used to treat LSC but after withdrawal a relapse will sometimes occur. Therefore, LSC can be difficult to treat over time. We report a 13-year-old boy suffering from LSC on two symmetrical circumscribed areas on the temple, whose lesions healed completely with tacrolimus 0.1% ointment within approximately 9 months. During active treatment no adverse drug reaction was observed. The patient is completely free of symptoms 3 years after cessation of treatment. We conclude that topical tacrolimus can be used as an effective, long-lasting therapeutic modality in treating LSC, especially in sensitive skin areas such as the face.     

他克莫司对特应性皮炎皮损中蛋白酶活化受体2表达的影响

目的 观察蛋白酶活化受体2（PAR-2）在特应性皮炎（AD）患者皮肤中的表达以及他克莫司对其表达的影响。方法 比较6例中重度AD患者外用0.1%他克莫司软膏治疗3周前后的临床症状、体征变化,切取患者治疗前后皮损及外观正常的皮肤,6例正常皮肤作对照,免疫组化方法检测皮肤PAR-2的表达变化。结果 PAR-2在皮肤的表皮全层尤其是颗粒层以及毛囊、汗腺、血管内皮细胞、神经纤维样结构均表达。AD患者皮损内角质形成细胞PAR-2染色的平均吸光度为4339.6 ± 115.8,与非皮损部位（4189.0 ± 228.9）和正常对照皮肤（3864.0 ± 237.3）比较,其表达明显升高（t = 2.85,P < 0.05;t = 4.31,P < 0.05）;0.1%他克莫司软膏治疗3周后原皮损处角质形成细胞PAR-2染色的平均吸光度为3942.4 ± 176.6,表达较治疗前明显下降（t = 4.55,P < 0.05）;PAR-2的表达水平与AD患者的瘙痒VAS评分、EASI指数和IGA评分均呈正相关。 结论 PAR-2在AD患者皮损角质形成细胞内的表达增加,表达水平与瘙痒程度和皮损严重程度呈正相关,PAR-2在皮损角质形成细胞内的过度表达可被他克莫司抑制。     

Effects of tacrolimus ointment on Toll-like receptors in atopic dermatitis

Background. Alterations of Toll‐like receptors (TLRs) seem to play a role in susceptibility to atopic dermatitis (AD). Aim. To investigate the expression of TLRs in moderate to severe chronic AD in adults before and after a 3‐week treatment with 0.1% tacrolimus ointment, compared with 0.1% topical hydrocortisone‐17‐butyrate. Methods. In total, 21 adult patients with AD were enrolled: 11 were given tacrolimus ointment and 10 were given hydrocortisone butyrate; a further 6 healthy adults formed the control group. The clinical efficacy of the treatment was assessed using the SCORing Atopic Dermatis (SCORAD) index. Biopsies were taken from lesional skin before and after treatment, which were stained immunohistochemically with monoclonal antibodies to TLR‐1, ‐2, ‐4 and ‐9. Results. Both 3‐week topical treatments improved signs and symptoms in all 21 patients considered, with no significant difference between the two groups. In the skin of patients with AD, TLR‐1 was overexpressed and TLR‐2 underexpressed compared with healthy controls, whereas no differences were found for TLR‐4 and TLR‐9. Staining for TLR‐1 was decreased in both groups after treatment. AD specimens had higher levels of TLR‐2 expression after either treatment compared with baseline, and levels were higher after tacrolimus treatment than after hydrocortisone butyrate. Neither tacrolimus nor hydrocortisone butyrate affected expression of TLR‐4 or TLR‐9. Conclusion. Short‐term therapy with tacrolimus ointment reduced expression of TLR‐1, which may inhibit the antimicrobial potential of TLR‐2, and also reversed the impairment of TLR‐2 in AD lesions. Expression of TLR‐4 and TLR‐9 was not affected by tacrolimus.     

Annular erythematous papules in the neckline

A 45-year-old woman with personal history of hypertension presented with an erythematous lesion in the neckline for a year and with a progressive growth. A physical examination revealed an annular lesion with erythematous papules in the edge. Histological exam showed phagocytosis of elastic fibers by multinucleated cells compatible with annular elastolytic giant-cell granuloma. The patient did not present any other associated systemic manifestation. Treatment with tacrolimus 0.1 percent ointment was prescribed with a very good response after two months.