A prospective, open-label, non-comparative study of ambrisentan with anti-fibrotic agent combination therapy in the treatment of diffuse systemic sclerosis.

BACKGROUND: Systemic Sclerosis is a multifactorial autoimmune rheumatic disease characterized by inflammation, fibrosis, immune dysregulation and vascular dysfunction. METHODS: An open label, prospective, non-comparative study evaluating ambrisentan with an antifibrotic agent in diffuse cutaneous systemic sclerosis (dcSSc). Recruited 15 consecutive patients with dcSSc who were already on a stable dose of an antifibrotic agent and if they met inclusion criteria they were initiated on ambrisentan 5 mg/day for 12 months. Primary outcome measure was the modified Rodnan skin score (mRSS) while secondary measures were the short form 36 (SF-36) questionnaire, the Medsger severity score and pulmonary function studies. RESULTS: Fifteen patients were recruited and ten patients completed all 12 months of the study. An intention to treat was used to analyze the data. There was statistical improvement of the mean mRSS and the perceived change in health component of the SF-36. The Medsger severity score and pulmonary function studies remained unchanged over the course of the study. CONCLUSION: Patients who tolerated the combination of an antifibrotic with ambrisentan had an improvement of their mRSS over the course of the study as well as an improvement of their perceived health. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01093885; March 2010.

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.

Primary amyloidosis causing diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage is a serious complication that has been described in various disease states including several vasculitic syndromes as well as conditions that may resemble vasculitis clinically. In this article, we present a case of 79-year-old man, who was admitted with productive cough, blood-tinged sputum, and a positive atypical antineutrophil cytoplasmic antibody pattern on indirect immunofluorescence microscopy. He subsequently developed frank hemoptysis and respiratory failure. Open lung biopsy demonstrated amyloid deposition within blood vessels. He was treated with 1 g of intravenous methylprednisolone over 3 days with rapid improvement in hemoptysis and hypoxemia. This case report and a review of literature illustrate unusual clinical manifestations of vascular amyloidosis that may be confused with vasculitis. Accurate diagnosis of this condition may improve clinical outcome and spare the patient from unwarranted, potentially harmful treatments.

Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors.

OBJECTIVES: To evaluate patients with systemic sclerosis (SSc) who have gastric antral vascular ectasia (GAVE), to further characterize this disease association, and to identify factors that may predict which patients with SSc are at greatest risk for the development of GAVE. METHODS: Patients with a diagnosis of both SSc and GAVE were identified from the Division of Rheumatology at Georgetown University and Thomas Jefferson University. A chart review was conducted to obtain the demographic data. RESULTS: Twenty-eight patients were included in this analysis, including 17 with diffuse cutaneous (dcSSc) and 11 with limited cutaneous SSc (lcSSc). The mean disease duration at diagnosis with GAVE was 21.5 months for dcSSc and 84.3 months for lcSSc (p = 0.025). Seventy-six percent of patients with dcSSc developed GAVE within 18 months of first scleroderma symptom onset. Over half of patients with early GAVE also had rapidly progressive cutaneous disease. Only 4% had antitopoisomerase I antibody. Although only 1 patient was tested and had positive RNA polymerase (RNAP) III, RNAP III may be overrepresented in this GAVE population. Mean hematocrit levels were 23.8% in dcSSc and 29% in lcSSc. CONCLUSION: dcSSc is associated with earlier development of GAVE, as well as more severe anemia requiring more therapeutic interventions. Rapid progression of cutaneous disease may suggest earlier development of GAVE. Absence of antitopoisomerase I antibodies and presence of antibodies to RNAP III/speckled antinuclear antibody pattern may be useful to identify the subset of patients with SSc with increased risk for GAVE.

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 use of mycophenolate mofetil for the treatment of systemic sclerosis.

Mycophenolate mofetil (MMF) is an inosine monophosphate dehydrogenase inhibitor, that inhibits the de novo pathway of guanosine nucleotide synthesis, the proliferative responses of T and B lymphocytes as well as antibody production by B-lymphocytes. It is indicated for the prophylaxis of organ rejection after allogeneic cardiac, hepatic and renal transplants . It has recently also been used with good success in patients with lupus nephritis . Based on these actions, MMF appears to be a novel agent for the treatment of systemic sclerosis, especially during early disease where an inflammatory infiltrate preceeds the development of fibrosis. Disease modification early on during the inflammatory stage of systemic sclerosis may lead to an overall decrease in fibrotic complications both in relation to cutaneous and internal organ involvement.