Initial presentation of acute transverse myelitis in systemic lupus erythematosus: demographics, diagnosis, management and comparison to idiopathic cases.

To describe and compare the diagnosis, demographics and management of systemic lupus erythematosus (SLE) related versus idiopathic acute transverse myelitis during the initial presentation of the disease. We undertook a chart review of the hospital records of patients admitted to our hospital from 1994 until 2007 and had the diagnosis of SLE related and idiopathic acute transverse myelitis. Demographics, laboratory and imaging studies, diagnosis and treatment were recorded in both groups and analyzed in a case control fashion. We identified 15 patients with SLE-related acute transverse myelitis (SLE-ATM) and 39 idiopathic (I-ATM) cases between 1994 and 2007. Patients with SLE were more likely to be African American, have CNS demyelinating lesions on MRI, a high IgG% on their CSF analysis and a higher sedimentation rate on presentation. Treatment with high-dose steroids was instituted in both groups of patients, though SLE patients had a longer hospital stay by an average of 5 days. SLE-ATM patients were more likely to be African American as compared to I-ATM patients, have CNS demyelinating lesions on MRI, a high IgG% on CSF analysis and a higher sedimentation rate on presentation. The hospital stay for SLE patients was 5 days longer than the idiopathic patients. This study underlines the importance of early diagnosis of patients who develop ATM related to SLE.

A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil for the treatment of SSc. METHODS: We recruited 15 patients with dcSSc to take part in an open-label study using mycophenolate mofetil to treat their disease over a 12-month period. The primary outcome measure was the modified Rodnan skin score (mRSS), whereas secondary outcomes included the Medsger severity score, pulmonary function studies, 2D echocardiograms and the Short Form Health Survey (SF)-36 questionnaire. RESULTS: The mRSS significantly improved in those patients who tolerated the medication for >3 months (P < 0.0001), and there was a statistically significant improvement in the Medsger severity scores of the general (P = 0.05), peripheral vascular involvement (P = 0.05) and skin (P = 0.0003) scores. The SF-36 scores improved (P = 0.05) and the pulmonary function studies showed a trend towards improvement, though not of statistical significance. The mean pulmonary artery pressure by 2D echocardiography did not change. CONCLUSIONS: In this prospective open-label study of mycophenolate mofetil for the treatment of dcSSc, we observed significant improvements in skin scores, peripheral vascular involvement and patient-perceived health status. Pulmonary function studies did not worsen as expected, but instead showed a trend towards improvement. Controlled trials are needed to further investigate this trend for improved pulmonary function studies.

The Role of MicroRNAs and Human Epidermal Growth Factor Receptor 2 in Proliferative Lupus Nephritis.

OBJECTIVE: To understand the roles of microRNAs (miRNAs) in proliferative lupus nephritis (LN). METHODS: A high-throughput analysis of the miRNA pattern of the kidneys of LN patients and controls was performed by molecular digital detection. Urinary miRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target gene expression in human mesangial cells was evaluated by arrays and qRT-PCR. Human epidermal growth factor receptor 2 (HER-2) was analyzed by immunohistochemistry in kidney samples from LN patients and in a murine model of lupus. Urinary levels of HER-2, monocyte chemotactic protein 1 (MCP-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Levels of the miRNAs miR-26a and miR-30b were decreased in the kidneys and urine of LN patients. In vitro these miRNAs controlled mesangial cell proliferation, and their expression was regulated by HER-2. HER-2 was overexpressed in lupus-prone NZM2410 mice and in the kidneys of patients with LN, but not in other mesangioproliferative glomerulonephritides. HER-2 was found to be up-regulated by interferon-α and interferon regulatory factor 1. Urinary HER-2 was increased in LN and reflected disease activity, and its levels correlated with those of 2 other recognized LN biomarkers, MCP-1 and VCAM-1. CONCLUSION: The kidney miRNA pattern is broadly altered in LN, which contributes to uncontrolled cell proliferation. Levels of the miRNAs miR-26a and miR-30b are decreased in the kidneys and urine of LN patients, and they directly regulate the cell cycle in mesangial cells. The levels of these miRNAs are controlled by HER-2, which is overexpressed in NZM2410 mice and in the kidneys and urine of LN patients. HER-2, miR-26a, and miR-30b are thus potential LN biomarkers, and blocking HER-2 may be a promising new strategy to decrease cell proliferation and damage in this disease.

The role and effect of complementary and alternative medicine in systemic lupus erythematosus.

The use of complementary and alternative medicine (CAM) is common among patients with systemic lupus erythematosus (SLE), especially those with active disease who often have poorer quality of life and significant unmet needs. It is important for the rheumatologist to be aware of these therapies and to ask the patient with SLE about their active use or future interest in CAM. Future studies on the effectiveness of the aforementioned therapies will be crucial to find better ways for the rheumatologist to integrate their use into the care of the patient with SLE.

Maternal mixed connective tissue disease and offspring with chondrodysplasia punctata.

OBJECTIVES: To describe the case of a mother with mixed connective tissue disease (MCTD) whose male and female offspring from 2 successive pregnancies had chondrodysplasia punctata (CDP) in the absence of identifiable biochemical or genetic abnormalities or teratogen exposure. METHODS: Description of a male and female offspring from a mother with MCTD harboring high-titer anti-ribonucleoprotein (RNP) antibodies. Maternal autoantibody assays were performed employing quantitative multiplex suspension arrays and flow cytometry, and autoantibody titer and pattern were determined by indirect immunofluorescence. Assays of phytanic acid, plasmalogen, and very long-chain fatty acids were performed employing commercially available reagents. Chromosomal analysis was performed on both offspring employing standard cytogenetic analysis. Review of the relevant literature was performed (PubMed search 1966 through July 2008). RESULTS: Two children with CDP born to a mother with MCTD who harbored anti-RNP autoantibodies at high titer are described. Genetic and chromosomal studies and biochemical analysis of peroxisome function and very long-chain fatty acids excluded known biochemical or genetic defects or mutations as the cause of CDP in these children. Furthermore, detailed review of the clinical history failed to disclose any evidence of maternal teratogen exposure during the 2 pregnancies. CONCLUSIONS: Maternal MCTD is the most likely explanation for the occurrence of CDP in the 2 children reported here. Review of previously published cases of CDP associated with autoimmune disease suggests that placental crossing of maternal autoantibodies during pregnancy specifically affecting the normal development of fetal growth plates is responsible for CDP in the offspring in these cases.

Improvement of severe systemic sclerosis-associated gastric antral vascular ectasia following immunosuppressive treatment with intravenous cyclophosphamide.

OBJECTIVE: We describe 3 patients with systemic sclerosis (SSc) with severe, transfusion-dependent gastric antral vascular ectasia (GAVE) refractory to laser ablation who showed remarkable clinical and endoscopic improvement following intravenous (IV) pulse cyclophosphamide (CYC) treatment. METHODS: Review of clinical records and upper gastrointestinal endoscopy images from 3 patients with SSc and severe GAVE before and after treatment with IV pulse CYC. RESULTS: IV CYC was followed by improvement and stabilization of hemoglobin levels, and marked reduction in blood transfusion requirements and the number and frequency of endoscopic laser treatments. CONCLUSION: IV pulse CYC immunosuppression was followed by remarkable clinical and endoscopic improvement of SSc-associated GAVE.

Scleroderma lung disease: treatment with cyclophosphamide.

Evaluation of: Tashkin, Elashoff, Clements PJ et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 354(25), 2655-2666 (2006). Interstitial lung disease has become one of the leading causes of morbidity and mortality in systemic sclerosis. Currently, there remains a void in proven effective treatment strategies to provide clinical benefit to affected patients. The article under evaluation pioneers the efforts of investigating oral cyclophosphamide in treating scleroderma lung disease by designing a prospective, double-blinded, placebo-controlled study examining the drug's effect on outcome measures of forced vital capacity, patient subjective health assessment questionnaire disability scores, among others. We review the methods, results and overall conclusion of the study, which shows a significant, yet modest, result demonstrating the benefit of oral cyclophosphamide in the context of this disease setting. We conclude that although the study provides an excellent starting point for examining the efficacy of cyclophosphamide in certain forms of scleroderma lung disease, the study's high drop-out rate, choice of forced vital capacity as a primary outcome, side-effect profile of the drug and overall significance of the results make the conclusions difficult to incorporate into clinical practice.