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.     

PUVA-cream photochemotherapy for the treatment of localized scleroderma

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.     

Ultraviolet A1 phototherapy for the treatment of localized scleroderma

Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1 phototherapy is also effective against the sclerotic lesions of systemic sclerosis and morphea. Currently, in Japan, access to UVA1 phototherapy is limited because the UVA1 phototherapy device has not yet been approved. On the basis of our experience, we report three patients with localized scleroderma who responded successfully to UVA1 phototherapy. Efficacy was assessed by histological analysis and elastography. UVA1 successfully ameliorated sclerotic lesions, including morphea, linear scleroderma and morphea lesions in a patient with limited cutaneous systemic sclerosis. No side-effects were observed during UVA1 phototherapy.     

局限性硬皮病病情评估和治疗进展

局限性硬皮病是一种以局限性皮肤及皮下组织纤维化为特征的疾病.目前缺乏统一的病情评估标准,有作者提出多种评估方法,如半定量评分及利用计算机进行评分,并研究了激光多普勒血流仪、超声、磁共振在该病评估中的作用.治疗主要集中在免疫调节和抗纤维化方面,近年来评估了多种药物的疗效,如他克莫司、咪喹莫特、甲氨蝶呤和波生坦等,光疗也得到广泛应用.因此,文中总结近年来局限性硬皮病病情评估和治疗方面的研究进展.     

局限性硬皮病发病机制的研究进展

局限性硬皮病是一种以局部皮肤及皮下组织纤维化为特征的疾病.病因不明,发病机制可能涉及小血管的损伤、T细胞的活化以及结缔组织生成增加等多个过程.T细胞活化释放各种细胞因子,趋化因子,主要包括肿瘤坏死因子α、转化生长因子β、可溶性白细胞介素受体2和可溶性白细胞介素受体6等.血管内皮细胞的损伤也可介导纤维化相关的细胞因子释放.局限性硬皮病和系统性硬皮病在发病机制上有一定的区别和联系,概述局限性硬皮病发病机制的最新进展.     

Longitudinal melanonychia in localized scleroderma

Longitudinal melanonychia associated with scleroderma is rare. This is paradoxical, as increased skin pigmentation is frequent in the latter disease. This article reports 4 cases of longitudinal melanonychia that were found concurrently with various types of localized scleroderma. These 4 cases may be a coincidental finding despite the fact that pigmentation is so frequent a manifestation of scleroderma. In 2 cases, biopsy specimen of the nail matrix showed well-defined melanocytes without cellular atypia. This, in keeping with the pigmentation of scleroderma, appears to result from the functional activation of the matrix melanocytes.     

Systemic and localized scleroderma

Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.     

Nodular scleroderma in systemic sclerosis under D-penicillamine therapy.

A case of systemic sclerosis (SS) which developed keloidal lesions (nodular scleroderma) on the chest during D-penicillamine (DPC) therapy is reported. The 36-year-old woman showed rapidly progressing skin sclerosis with lung and esophageal involvement, and DPC was started at the age of 38. Skin sclerosis as a whole had improved to some extent, when keloidal nodules developed on the upper chest at the age of 44. Since there were no other findings suggestive of adverse reactions caused by DPC, we speculate that activation of the fibroblasts in these lesions occurred despite the suppressive effect of DPC.     

Rheumatoid factor isotypes in localized scleroderma

Localized scleroderma is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with localized scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or normal controls (P < 0.0005). The levels of IgG RF were significantly higher in patients with GM than normal controls (P < 0.05). The levels of IgA RF were significantly higher in patients with GM or LS than normal controls (P < 0.001 and P < 0.01, respectively). The count of sclerotic lesions was significantly higher in patients with IgM RF than those without (P < 0.05). These results suggest that the presence of RF isotypes is one of the immunological abnormalities of localized scleroderma. IgM RF seemed to be most useful of these three factors to determine the severity of disease.     

Treatment options for localized scleroderma

Localized scleroderma, or morphea, is a chronic disease that causes a thickening and induration of the skin. For plaque type morphea, the treatments of choice include super-potent corticosteroids and calcipotriol. For the more generalized forms, as well as the linear forms, UVA is currently the best therapeutic modality. Patients with localized scleroderma are managed by both rheumatologists and dermatologists. There is still much therapeutic uncertainty in this disease.     

Histological study on localized scleroderma

To define stage-specific and type-specific histological findings in morphea, 21 (14 plaque, 2 linear, and 5 en coup de sabre type) patients were examined. A) Fibrotic changes; 1) Every case had the fibrotic change of various degrees. 2) Nodular sclerotic fibrosis was found in 7 cases with morphea, namely in 5 of 11 cases with a plaque type and 2 of 4 en coup de sabre type morphea. And the above mentioned 7 cases were within two years since the onset, and no nodular fibrosis was found in the morphea with the longer duration than two years in history. Nodular fibrosis was located in the middle or lower dermis adjacent to the typical sclerotic dermis. It was strongly suggested that this nodular fibrosis is as an initial change of localized scleroderma. 3) Nodular fibrosis expanded to the neighboring area and made a typical histological feature of morphea which is completely different from that of diffuse scleroderma. B) Inflammatory findings; 1) Inflammatory changes were divided into, a perivascular, a diffuse or non-perivascular, and a mixed type. 2) The pure perivascular type was found in 10, the pure diffuse type only in one, the mixed type in 6 cases, and the other 4 cases had no inflammation. 3) Marked or moderate inflammation was found in cases with short history of the disease except for one case. 4) Inflammatory cells in the morphea were mainly composed of lymphocytes and histiocytes, but occasionally of plasma cells in 11 of 17 cases. C) Pigmentary changes; Incontinentia pigmenti was found in 18 of 21 cases.     

Immunohistochemical characterization of the cellular infiltrate in localized scleroderma

Background Localized scleroderma is a connective tissue disorder with hardening of the skin and fibrosis of the affected tissue as the most prominent features. The etiology of localized scleroderma is still unknown, but immunologic factors may play an important role in the pathogenesis. This study was performed to determine the immunohistochemical features of the cellular infiltrate in localized scleroderma. Methods Skin samples were obtained from six patients by 6‐mm punch biopsy. The samples were stained with monoclonal antibodies against CD1a, CD3, CD4, CD8, CD20, CD25, CD30, and CD57. The number of cells stained with each monoclonal antibody was calculated. Results There were more CD1a+, CD3+, CD4+, CD8+, CD20+, CD25+, and CD57+ cells in the dermal infiltrate in localized scleroderma relative to those in normal controls. The numbers of CD1a+, CD3+, CD4+, CD8+, and CD57+ cells in localized scleroderma were significantly greater than those in normal skin (P < 0.05). The number of CD30+ cells in localized scleroderma was almost the same as that in normal skin. Conclusions This study reveals that T lymphocytes, Langerhans cells, and natural killer cells may play important roles in the pathogenesis of localized scleroderma.     

局限性硬皮病病因和发病机制研究进展

局限性硬皮病是一种以局限性皮肤及皮下组织纤维化为特征的疾病.病因未明,可能与多种因素有关.其发病机制涉及血管改变、免疫系统活化和失调、成纤维细胞活化和纤维化,与血管内皮细胞受损、自身免疫、微嵌合性、转化生长因子β、结缔组织生长因子、胰岛素样生长因子、基质金属蛋白酶类及其组织抑制因子、活性氧簇等有关.