Steffan W. Schulz

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.

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.

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.

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

To understand the roles of microRNAs (miRNAs) in proliferative lupus nephritis (LN).

The Gastrointestinal Manifestations of Systemic Lupus Erythematosus: A Survey of the Literature

Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with auto-antibody production and resulting widespread inflammation that has potential to affect and damage many organ systems. Gastrointestinal manifes- tations of SLE are well documented in the literature but the exact extent and frequency of their presence is likely grossly underestimated. Patients present with vague complaints such as abdominal pain and nausea with non-specific physical exam findings and inconclusive diagnostic tests and serologic analysis. Recent research has helped to better clarify these manifestations of SLE and has demonstrated distinct involvement of almost every portion of the GI tract. This article is based upon an exhaustive review of the literature from 1976 to present date and summarizes the major advances in the identification and differentiation of gastrointestinal incarnations related to systemic lupus erythematosus. The review also encompasses theories of etiology of the various manifestations, summarizes accepted and experimental treatment regi- mens, and highlights the differential diagnosis of each presented topic, including disorders of the oropharynx, esophagus, stomach, small and large intestine, liver and gallbladder and beyond.

Systemic sclerosis at the cellular level: molecular pathways of pathogenesis and its implication on future drug design.

Endothelial cell abnormalities and the effects on the surrounding microvasculature is a focal point in the pathogenesis of Systemic Sclerosis disease and may even be the sentinel event for the initiation of this disorder. A better understanding of these processes may improve our understanding of the pathophysiology of Systemic Sclerosis and more specifically the vasculopathy observed. Such knowledge will help us to further current treatments options and design novel therapies for Systemic Sclerosis and other fibrotic disorders.

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.