Summary The objective of the study was to investigate the role of endothelin-1 in the pathogenesis of scleroderma renal crisis in patients with systemic sclerosis. We used immunohistochemical ...analysis with anti–endothelin-1 and anti–von Willebrand factor antibodies in comparing kidney biopsies from patients with systemic sclerosis and scleroderma renal crisis (n = 14); from normal kidneys (n = 5); and from patients with typical hemolytic uremic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosporine toxicity (n = 5), or nephroangiosclerosis (n = 5). Kidney biopsies from all systemic sclerosis patients presented specific lesions: glomerular lesions with thickened capillary walls (n = 6, 42.8%), mesangiolysis (n = 3, 21.4%), fibrin thrombi (n = 3, 21.4%), hypertrophy of juxtaglomerular apparatus (n = 5, 35.7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (n = 13, 92.8%), proliferation of intimal cells (ie, “onion-skin” lesions; n = 13, 92.8%), fibrinoid necrosis (n = 3, 21.4%), and fibrin thrombosis (n = 4, 28.6%). Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92.8%). The pattern of endothelial staining for endothelin-1 in both glomeruli and arteriolar lesions appears to be specific for scleroderma renal crisis. Glomerular endothelin-1 staining without arteriolar staining was seen in hemolytic uremic syndrome; and isolated arteriolar staining (without glomerular staining) was seen in a number of conditions including antiphospholipid nephropathy, cyclosporine toxicity, and diabetic nephropathy. Endothelin-1 is overexpressed in glomeruli and arterioles of patients with scleroderma renal crisis, which suggests that endothelin-1 might be a therapeutic target in this condition.
Little is known about systemic sclerosis (SSc)-associated myopathy (SScAM) treatment. Herein we evaluated the use of intravenous immunoglobulin (IVIg) in SScAM.
We conducted a retrospective study of ...patients with SScAM in the Internal medicine department of Cochin University Hospital between 1993 and 2017.
Fifty-two patients were included comprising 18 (34.6%) with limited SSc and 34 (65.4%) with diffuse SSc. SScAM occurred at a median interquartile range (IQR) time of 1 month 0–15 after SSc diagnosis. Thirty-four patients (65.4%) had muscle weakness, 28 (53.8%) had myalgia and 24 (46.2%) had dysphagia. Fifty patients (96.2%) had increased creatine kinase, 22/26 (84.6%) had myopathic electromyography, 10/12 (83.3%) had a high intensity signal of girdle muscles on MRI and 49/50 (98%) had abnormal muscle biopsy. Eighteen (34.6%) patients received IVIg. Severe adverse events occurred in 3/18 (16.7%) patients. When compared to patients who did not receive IVIg, patients who received IVIg had a significantly higher maximal corticosteroid (CS) dose ever, a greater decrease of CS at 3 months, and a lower CS dose at one year and at the end of follow up.
This study suggests the benefit of IVIg as adjunctive therapy, with an acceptable tolerance profile, and supports its use as a CS-sparing agent, in SScAM.
•This study reports 52 cases of systemic sclerosis-associated myopathy (SScAM).•IVIg can be used as an adjunctive therapy in SScAM.•Is has an acceptable tolerance profile and is used as a CS-sparing agent, in SScAM.
Objective. Scleroderma renal crisis (SRC) is a severe manifestation of SSc, whose prognosis remains severe, despite treatment with angiotensin-converting-enzyme inhibitor and dialysis. This study was ...undertaken to describe SRC characteristics, prognosis and outcome, and evaluate the responsibility of CSs in its occurrence.
Methods. Analysis concerned 91 SSc patients with SRC who were compared with 427 non-SRC-SSc patients taken as controls.
Results. Among the 91 SRC patients, 71 (78.0%) had high blood pressure, 53 (58.2%) hypertensive encephalopathy and 51 (56.0%) thrombotic microangiopathy; 64 (70.3%) had received CSs before or concomitantly with SRC vs 156 (36.5%) non-SRC-SSc patients (P < 0.001). Treated SRC patients also received more prednisone 29.3 (28.4) vs 3.6 (9.9) mg than controls (P < 0.001). SRC clinical outcomes were poor: 49 (53.8%) patients required dialysis, which was definitive for 38. Thirty-seven (40.7%) SRC patients died vs 10.8% of the controls (P < 0.001). Death was most frequent among dialysed patients who never recovered renal function (22 vs 2) and 13 never-dialysed SRC patients died.
Conclusions. Although SRC prognosis has improved markedly, SRC remains a severe manifestation of SSc, despite treatment with angiotensin-converting enzyme inhibitor and dialysis. CSs contributed significantly to SRC occurrence.
To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc).
...Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off≥8).
9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed.
High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations.
To assess the sensitivity to change of the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR) in systemic sclerosis (SSc) and a shift in patient priorities over time.
We ...assessed 49 patients with SSc (8 men) using the MACTAR in a prospective longitudinal study twice or more during annual meetings of the French patient association from 2004 to 2007. Patient-perceived improvement or worsening regarding health status was recorded. Sensitivity to change was assessed by the effect size (ES) and the standardized response mean (SRM) of the MACTAR.
The MACTAR global score was significantly increased at followup in the whole group of patients, and the ES and SRM values were -0.37 and -0.34, respectively. These values were similar to those observed for widely used outcome measures for SSc such as the Health Assessment Questionnaire. As defined by the International Classification of Functioning, Disability and Health, the 3 disability domains most often cited at baseline were mobility (7 activities, cited 17 times; 33.3% of patients), domestic life (4 activities, cited 17 times; 33.3% of patients), and community, social and civic life (3 activities, cited 10 times; 19.6% of patients). At followup, 40 patients had changed their first priority and 34 changed 3 priorities.
The evolution in MACTAR global score over time for patients with SSc reflects longterm general feelings of deterioration. However, shifts in patient priorities are common and may influence the sensitivity to change of the instrument.
Abstract Patients with antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AASV) commonly suffer from arthralgias and, sometimes, polyarthritis during disease flares. Although ...rheumatoid factor (RF) can be detected in up to 37–50% of AASV patients, anti-cyclic citrullinated peptide (anti-CCP) antibodies are rare. Herein, we describe the clinical features of five P-ANCA–positive vasculitis patients, who had persistent and/or high anti-CCP levels and, more importantly, suffered from remittent non-destructive arthralgias and polysynovitis, independently of the vasculitis course and without evidence of RA. Two were initially thought to have RA rather than microscopic polyangiitis and, at AASV diagnosis, all had kidney involvement and three had alveolar hemorrhages. With a median follow-up of 30 months, one suffered vasculitis relapses, preceded by polysynovitis, and others had remittent arthralgias and polysynovitis, while their vasculitides remained in remission. None of these patients had radiological destructive arthritis. We discuss the challenge of diagnosing these patients positive for anti-CCP and ANCA, and with dominant articular manifestations. AASV patients with anti-CCP antibodies may experience relapsing polysynovitis and non-erosive polyarthritis prior to vasculitis flares, but also independently of the vasculitis course, which is uncommon in AASV, and might represent a small subgroup of AASV patients.
In the 1980's, pregnancies in systemic sclerosis (SSc) patients were considered to be at high risk for poor foetal and maternal outcome. Retrospective studies found an increased frequency of pre-term ...births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis. The use of ACE inhibitors is recommended in this case despite the risk of teratogenicity. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc who are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. Hydroxychloroquine and low doses of steroids may be safely used. In order to minimize risks, a multidisciplinary approach is necessary to suggest the best timing for a pregnancy and provide adequate supportive treatment to SSc patients during the pregnancy.
Background. Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic ...infections (OIs). Methods.The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. Results.Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4+T cell count < 200×106cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P=.004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4+T cell counts (158×106vs 604×106cells/L; P<.001) and a severe defect in naive CD45RA+CCR7+CD4+T cell counts (<20% of total CD4+T cells in 71% of patients with LOCID vs 37% of patients with CVID; P=.001). The CD19+B cell compartment was also significantly decreased (20×106vs 102×106cells/L; P<.001). Conclusions.LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.
Objective
Myocardial involvement may occur during systemic sclerosis (SSc) and can lead to impaired myocardial contraction and/or arrhythmia. Cardiac magnetic resonance imaging (MRI) is used for ...noninvasive characterization of the myocardium. The aim of this study was to evaluate the utility of cardiac MRI with intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and longitudinal relaxation time (T1) sequence mapping for assessment of myocardial microvascular and interstitium impairment in SSc.
Methods
In this single‐center prospective cohort study, 40 consecutive patients with SSc and 20 healthy controls were assessed by cardiac MRI with IVIM DWI and T1 mapping sequences on a 3T scanning system. Images were analyzed independently by 2 assessors, and Bland‐Altman plots were used to assess interreader concordance and reproducibility. Characteristics of the patients were compared according to quartiles of T1 and perfusion fraction (f‐coefficient) values, using exact Cochran‐Ermitage trend tests for qualitative variables and analysis of variance for quantitative variables. Kaplan‐Meier cardiac events–free survival curves were plotted and compared with a log‐rank test for trend.
Results
T1 values were higher in SSc patients than in healthy controls, and were higher in the diffuse cutaneous SSc (dcSSc) subset (P = 0.02). Higher T1 values were associated with the immunologic pattern seen in patients with the dcSSc form (P = 0.0001), a higher modified Rodnan skin thickness score (MRSS) (P = 0.003), and a higher frequency of interstitial lung disease (P = 0.03). Moreover, higher T1 values were correlated with higher MRSS scores (r = +0.32, P = 0.04) and reduced forced vital capacity (r = −0.34, P = 0.048), and tended to be correlated with reduced total lung capacity (r = −0.30, P = 0.07). Lower f‐coefficient values, as a measure of decreased tissue perfusion, were associated with less frequent use of vasodilators (P = 0.02 for angiotensin‐converting enzyme inhibitors and P = 0.06 for calcium‐channel blockers) and more frequent use of glucocorticoids (P = 0.02). The f‐coefficients were inversely correlated with the T1 values (r = −0.31, P = 0.02). Furthermore, higher T1 values were associated with higher incidence of cardiac events (log‐rank test for trend P = 0.03).
Conclusion
Increased T1 values, potentially suggesting microscopic fibrosis, were observed more frequently in patients with dcSSc, and higher T1 values were associated with interstitial lung disease and more frequent cardiac events during follow‐up. The results of this study show that cardiac MRI with T1 mapping sequences and IVIM DWI may be useful in assessing myocardial involvement in patients with SSc.
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