Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients

In this study, we determined the adiponectin expression in the serum and lesional skin of patients with scleroderma (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis patients and 13 healthy subjects with specific enzyme-linked immunosorbent assays. Adiponectin mRNA was determined in skin tissues of five patients with diffuse cutaneous SSc (dcSSc), seven patients with limited cutaneous SSc (lcSSc) and seven healthy subjects with real-time polymerase chain reaction. There was a significant reduction in serum adiponectin levels in patients with dcSSc. SSc patients with decreased serum adiponectin levels had higher total skin thickness score and higher incidence of pulmonary fibrosis. Adiponectin mRNA levels in skin tissues from patients with dcSSc were also reduced. Serum adiponectin levels may be a useful biomarker for fibrotic condition in patients with SSc. Clarifying the role of adiponectin in collagen diseases may lead to further understanding of the pathogenesis and new therapeutic approach.     

来氟米特治疗难治性结缔组织病15例疗效观察

目的：观察来氟米特治疗难治性结缔组织病的疗效。方法：应用小剂量来氟米特(20mg/d)开放性治疗15例难治性结缔组织病患者，包括系统性红斑狼疮(10例)、皮肌炎(4例)、白塞病(1例)。结果：对于常规治疗无效的顽同难治性患者，应用小剂量来氟米特疗效显著，能控制病情，减少糖皮质激素用量。结论：来氟米特为难治性结缔组织病提供了一种较好的治疗方案。     

Undifferentiated connective tissue disease and its cutaneous manifestations

Undifferentiated connective tissue disease (UCTD, also named UCT syndrome, latent lupus or incomplete lupus) is regarded as an autoimmune disorder in which signs and symptoms are widely variable and evocative for connectivitis but not sufficiently evolved to fulfil any of the accepted classification criteria for the defined connective tissue diseases. In this paper we describe the case of a 47-year-old woman affected by UCTD according to the preliminary classification criteria supplied by Mosca et al. in 1999.     

Bullous systemic lupus erythematosus in a 6‐year‐old boy

Bullous systemic lupus erythematosus (BSLE) is a rare subepidermal blistering disorder characterized by an acute vesiculobullous eruption in a subset of individuals with systemic lupus erythematosus. BSLE most commonly affects young women and only rarely affects children. Herein we report a rare case of BSLE in a 6‐year‐old boy.     

Lupus erythematosus and other autoimmune diseases related to statin therapy: a systematic review

BACKGROUND: Statins have been increasingly associated with drug-induced autoimmune reactions, including lupus erythematosus. OBJECTIVE: To identify and determine the clinical and biological characteristics of statin-induced autoimmune reactions. MATERIAL AND METHODS: The MEDLINE database (1966 to September 2005) was used to identify all reported cases of statin-induced autoimmune diseases. The keywords used were statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, adverse effects, autoimmune disease, lupus erythematosus, dermatomyositis and polymyositis. RESULTS: Twenty-eight cases of statin-induced autoimmune diseases have been published so far. Systemic lupus erythematosus was reported in 10 cases, subacute cutaneous lupus erythematosus in three cases, dermatomyositis and polymyositis in 14 cases and lichen planus pemphigoides in one case. Autoimmune hepatitis was observed in two patients with systemic lupus erythematosus. The mean time of exposure before disease onset was 12.8+/-18 months; range 1 month-6 years. Systemic immunosuppressive therapy was required in the majority of cases. In many patients, antinuclear antibodies were still positive many months after clinical recovery. A lethal outcome has been recorded in two patients despite aggressive immunosuppressive therapy. CONCLUSION: Long-term exposure to statins may be associated with drug-induced lupus erythematosus and other autoimmune disorders. Fatal cases have been reported despite early drug discontinuation and aggressive systemic immunosuppressive therapy.     

Transforming growth factor β‐inhibitor Repsox downregulates collagen expression of scleroderma dermal fibroblasts and prevents bleomycin‐induced mice skin fibrosis

Inhibition of transforming growth factor (TGF)‐β1 signalling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been many basic researches of TGF‐β blockade reagents, few of them were proved to have inhibitory effects on fibrosis both in vitro and in vivo. In this study, we randomly chose four commercially available low molecular weight compounds (Repsox, LY2109761, LY364947 and K02288) from TGF‐β1 inhibitor library, and compared their antifibrotic effects in vitro and in vivo. We demonstrated that Repsox has the most potent inhibitory effects on TGF‐β‐induced expression of CTGF and collagen of cultured normal dermal fibroblasts in vitro and their constitutive overexpression of scleroderma fibroblast in vitro. In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the downregulation of CTGF or collagen. Our results may facilitate clinical trial of Repsox against fibrotic diseases in future.     

Elevated serum MFG‐E8 level is possibly associated with the presence of high‐intensity cerebral lesions on magnetic resonance imaging in patients with systemic lupus erythematosus

Human milk fat globule‐EGF factor 8 (MFG‐E8), also known as lactadherin, is a secreted glycoprotein that plays essential roles in the clearance of apoptotic cells and angiogenesis. It has been reported that serum MFG‐E8 levels are higher in systemic lupus erythematosus (SLE) patients compared with in healthy controls; however, a previous study reported no correlation between serum MFG‐E8 levels and SLE disease activity. The objective of this study was to assess serum MFG‐E8 levels and their clinical associations in patients with SLE. Serum MFG‐E8 levels in 49 Japanese patients with SLE, eight with cutaneous LE, and 28 healthy controls were examined. Serum MFG‐E8 levels in SLE patients were significantly higher than those in cutaneous LE patients and healthy individuals. In addition, serum MFG‐E8 levels were positively correlated with the SLE Disease Activity Index score, which reflects the disease activity of SLE. Notably, the frequency of the presence of high‐intensity cerebral lesions on MRI in the SLE patients with elevated serum MFG‐E8 levels was significantly higher than that in SLE patients with normal serum MFG‐E8 levels. These findings suggest that elevated serum MFG‐E8 levels may be associated with cerebrovascular diseases or neuropsychiatric SLE in patients with SLE, and that the measurement of serum MFG‐E8 levels in SLE patients is useful for risk stratification of cerebrovascular disease or cerebrovascular disease‐related neuropsychiatric SLE.     

Serum levels of matrix metalloproteinase‐13 in patients with eosinophilic fasciitis

Matrix metalloproteinase‐13 (MMP‐13), a member of the collagenase family, has been implicated in the pathogenesis of connective tissue diseases characterized by extracellular matrix remodeling. Since serum MMP‐13 levels reflect disease severity of systemic sclerosis and localized scleroderma, we evaluated the clinical significance of serum MMP‐13 levels in eosinophilic fasciitis (EF). All the EF patients had serum MMP‐13 levels lower than the mean – 2SD of healthy controls. Serum MMP‐13 levels were also significantly decreased in EF patients compared with diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, and generalized morphea patients. Although serum MMP‐13 levels did not reflect any clinical and serological features of EF, these results indicate that MMP‐13 may be involved in the development of this disease.     

Advances in the management of UVR-associated skin cancers: autoimmune diseases and UV protection

Ultra violet radiation (UVR) is an important feature for the development or aggravation of several dermatologic diseases. In autoimmune skin diseases it has been suggested as an important cofactor in autoimmune bullous skin diseases and more importantly cutaneous lupus erythematosus (CLE). The pathophysiological role of UVR in CLE is a result of several effects which are triggered by UVR. In detail UVR induces apoptosis of keratinocytes and an abnormal local immune response which triggers inflammation in the skin. These findings result in the clinical approach of a stringent UVR protection in affected patients. Currently UVR protection is advised to patients as a supportive measure but cannot be prescribed to patients as these products are not licensed. Well-defined prospective placebo controlled studies regarding UVR protection are missing.     

Ten‐year retrospective clinicohistological study of cutaneous lupus erythematosus in Korea

An understanding of the differences in clinical manifestations and laboratory abnormalities between subtypes of cutaneous lupus erythematosus (CLE) is still lacking. The purpose of this study was to analyze demographic, clinical and histological features of CLE according to three main presentation subsets: acute (ACLE), subacute (SCLE) and chronic (CCLE). A 10‐year retrospective analysis was performed on data from patients who were diagnosed with CLE between March 2005 and September 2015 in a Korean tertiary referral dermatology clinic. We compared demographic data and clinical and histological findings between three different CLE groups. An overall sample of 220 patients with CLE consisted of 67 patients with ACLE, 25 patients with SCLE and 135 patients with CCLE. Patients with CCLE regardless of systemic lupus erythematosus (SLE) presence had lower prevalence of anemia, urinary abnormalities and elevated erythrocyte sedimentation rate. Furthermore, CCLE patients who only had skin lesions showed lower female predominance, lower extracutaneous manifestation, fewer laboratory and immunological abnormalities including low antinuclear antibody titers and the lowest positivity for C3, C4 and anti‐dsDNA, anti‐Ro, anti‐Sm and anti‐RNP antibodies, and more prominent perieccrine inflammation and dermal fibrosis in histological findings. Considering distinct cutaneous manifestations of LE, a comprehensive awareness of each CLE subtype is important for achieving a favorable prognosis through appropriate diagnosis and management. This study provides comparative clinical and histological profiles of patients with different CLE subtypes in Korea.     

Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients

BACKGROUND: The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE. OBJECTIVES: To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE. METHODS: One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student's t-test using SPSS 11 software. RESULTS: MTX led to a highly significant (P < 0.01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia (< 1.0 x 10(9) cells L(-1)) prior to MTX treatment. CONCLUSIONS: Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention to side-effects and contraindications.     

Drug‐induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine

Drug‐induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50–70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low‐risk drug and very few cases have been reported in children. We describe the case of CBZ‐induced SLE in a 9‐year‐old girl following 3 years of CBZ therapy. This case report shows that drug‐induced SLE is an important side‐effect to be considered, even after long‐term treatment with CBZ, and also during childhood.     

Serum interleukin‐34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease

Interleukin (IL)‐34 is a hematopoietic cytokine promoting proliferation and differentiation of macrophages. Because abnormal activation of macrophages is involved in the development of systemic sclerosis (SSc), we investigated serum IL‐34 levels in patients with SSc. Serum IL‐34 levels were significantly increased in diffuse cutaneous SSc compared with limited cutaneous SSc and healthy controls, while there were no significant differences between limited cutaneous SSc and healthy controls. In addition, SSc patients with increased serum IL‐34 levels more often had interstitial lung disease (ILD) than those with normal levels. Moreover, in SSc patients, serum IL‐34 levels negatively correlated with the percentage of predicted vital capacity, while they positively correlated with ground‐glass opacity score and fibrotic score on chest computed tomography. Collectively, increased serum IL‐34 levels were associated with greater frequency and severity of ILD in SSc patients. Serum IL‐34 levels may be a useful serological marker for SSc‐associated ILD.     

The wound/burn guidelines – 4: Guidelines for the management of skin ulcers associated with connective tissue disease/vasculitis

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Lupus erythematosus tumidus is a separate subtype of cutaneous lupus erythematosus

Background  Lupus erythematosus tumidus (LET) is a rare disease which was first described in 1909 but has not always been considered as a separate entity of cutaneous lupus erythematosus (CLE) in the international literature.
Objectives  To compare characteristic features of different subtypes of CLE and to analyse whether LET can be distinguished as a separate entity in the classification system of the disease.
Methods  The study involved 44 patients with CLE, including 24 patients with LET, 12 with discoid lupus erythematosus (DLE) and eight with subacute CLE (SCLE), from two centres in Germany. A core set questionnaire and an SPSS database were designed to enable a consistent statistical analysis.
Results  Location of skin lesions did not differ significantly between the CLE subtypes; however, the activity score was significantly lower in LET than in DLE ( P  <   0·01), and the damage score was significantly lower in LET than in SCLE ( P  <   0·01) and DLE ( P  <   0·01). Photosensitivity and antinuclear antibodies were confirmed to be different in LET compared with SCLE and DLE but without statistical significance. Moreover, histological analysis of skin biopsy specimens showed that abundant mucin deposition is significantly more present in LET compared with SCLE ( P  <   0·01) and DLE ( P  <   0·01) while prominent interface dermatitis and alteration of hair follicles were absent in LET.
Conclusions  Several significant differences were found between LET and other subtypes of CLE with regard to clinical, histological and laboratory parameters. These data strongly indicate that LET should be defined as a separate entity in the classification of CLE.     

Successful experience of rituximab therapy for systemic sclerosis‐associated interstitial lung disease with concomitant systemic lupus erythematosus

Previous studies have demonstrated that B cells play critical roles in autoimmune disorders including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). However, the effectiveness of rituximab (RTX), a chimeric anti‐CD20 antibody, for SSc‐associated interstitial lung disease (ILD) or SLE disease activity remains controversial. We herein report an SSc patient with severely progressed ILD and concomitant SLE treated by two cycles of RTX at baseline and half a year later. This treatment improved ILD and SLE activities, along with reduction of dermal sclerosis and serum anti‐topoisomerase I antibody levels. In addition, our detailed time‐course data indicate that half a year may be appropriate as an interval between each cycle of RTX therapy aimed at SSc‐associated ILD or SLE. Overall, the current report could pave the way to establish RTX as a disease‐modifying drug for patients with SSc and/or SLE showing resistance to other already approved medications.     

167例系统性红斑狼疮患者的临床及胸部影像学分析

目的：分析系统性红斑狼疮(SLE)患者的临床及胸部影像学改变，提高对本病的认识：方法：分析了167例确诊为SLE患者的临床及胸部X线平片改变．包括26例患者的CT片分析。结果：167例患者中胸部X线异常者89例(53．3％)，主要表现为双肺、心脏、胸膜和膈肌的改变。其中两种或两种以上改变并俘者65例(38．9％)。26例胸部CT检查均显示异常。部分影像学改变早于临床表现。结论：XLE的胸部X线及CT检查对早期胸部病变的诊断有参考价值，但由于相对缺乏特异性，需结合临床及实验室检查综合判断。