This study aimed to provide an updated analysis of the different prognostic trajectories of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies.
Among a cohort of 70 ...patients, baseline characteristics and phenotypes, treatments and outcomes were analyzed. A Cox proportional hazards model was used to identify factors associated with poor outcomes, i.e., death or progressive disease at the last follow-up.
Among the 70 patients, 45 were women, and 54 were Caucasian. A dermatologic involvement was observed in 58 (83%) patients, including 40 with MDA5 vasculopathy-related skin lesions. Muscular involvement was observed in 39 (56%) patients. Interstitial lung disease (ILD) was observed at baseline in 52 (74%) patients, including 23 (44%) who developed rapidly progressive (RP) ILD. Seven (10%) patients showed thromboembolic complications within the first weeks of diagnosis, and eight (11%) other patients developed a malignancy (4 before the diagnosis of anti-MDA5 disease). Poor outcomes were observed in 28 (40%) patients, including 13 (19%) deaths. Among the 23 patients with RP-ILD, 19 (79%) showed poor outcomes, including 12 (63%) who died. In multivariate analyses, RP-ILD (hazard ratio (HR), 95% CI: 8.24 3.21-22, p<0.0001), the occurrence of thromboembolic events (HR: 5.22 1.61-14.77, p=0.008) and the presence of any malignancy (HR: 19.73 6.67-60, p<0.0001) were the three factors independently associated with poor outcomes.
This new independent cohort confirms the presence of different clinical phenotypes of anti-MDA5 diseases at baseline and the poor prognosis associated with RP-ILD. Thromboembolic events and malignancies were also identified as prognostic factors.
Background:
Giant cell arteritis (GCA) is the most common systemic vasculitis. Relapses are frequent. The aim of this study was to identify relapse risk factors in patients with GCA with complete ...large-vessel imaging at diagnosis.
Methods:
Patients with GCA followed in our institution between April 1998 and April 2018 were included retrospectively. We included only patients who had undergone large vascular imaging investigations at diagnosis by computed tomography (CT)-scan and/or positron emission tomography (PET)-scan and/or angio-magnetic resonance imaging (MRI). Clinical, biological, and radiological data were collected. Relapse was defined as the reappearance of GCA symptoms, with concomitant increase in inflammatory markers, requiring treatment adjustment. Relapsing patients (R) and non-relapsing patients (NR) were compared. Relapse and multiple relapses (>2) risk factors were identified in multivariable Cox analyses.
Results:
This study included 254 patients (73.2% women), with a median age of 72 years at diagnosis and a median follow up of 32.5 months. At diagnosis, 160 patients (63%) had an inflammatory large-vessel involvement on imaging, 46.1% (117 patients) relapsed at least once, and 21.3% (54 patients) had multiple relapses. The median delay of first relapse after diagnosis was 9 months. The second relapse delay was 21.5 months. NR patients had more stroke at diagnosis than R (p = 0.03) and the brachiocephalic trunk was involved more frequently on CT-scan (p = 0.046), as carotids (p = 0.02) in R patients. Multivariate Cox model identified male gender hazard ratio (HR): 0.51, confidence interval (CI) (0.27–0.96), p = 0.04 as a relapse protective factor, and peripheral musculoskeletal manifestations HR: 1.74 (1.03–2.94), p = 0.004 as a relapse risk factor. Peripheral musculoskeletal manifestations HR: 2.78 (1.23–6.28), p = 0.014, negative temporal artery biopsy HR: 2.29 (1.18–4.45), p = 0.015, large-vessel involvement like upper limb ischemia HR: 8.84 (2.48–31.56), p = 0.001 and inflammation of arm arteries on CT-scan HR: 2.39 (1.02–5.58), p = 0.04 at diagnosis were risk factors of multiple relapses.
Conclusion:
Male gender was a protective factor for GCA relapse and peripheral musculoskeletal manifestations appeared as a relapsing risk factor. Moreover, this study identified a particular clinical phenotype of multi-relapsing patients with GCA, characterized by peripheral musculoskeletal manifestations, negative temporal artery biopsy, and large-vessel involvement with upper limb ischemia or inflammation of arm arteries.
Plain language Summary
At giant cell arteritis diagnosis, large-vessel inflammatory involvement is predictive of multiple relapses
46.1% of patients with GCA relapse, and 21.3% undergo multiple relapses;
Male gender appears as a protective factor for relapsing in GCA;
Peripheral musculoskeletal manifestations are a relapse and multiple relapses risk factor;
A negative temporal artery biopsy is predictive of multiple relapses;
Large-vessel involvement is predictive of multiple relapses.
Gamma heavy chain disease (γ-HCD) is a monoclonal gammopathy defined by an abnormal clonal and isolated production of incomplete heavy chain gamma (γ), unable to bind with light chains kappa or ...lambda. This disease is rare and remains poorly described. Its association to lymphoid neoplasm is well established, but exceptional forms of γ-HCD may also accompany auto-immune diseases. We report here a new case of γ-HCD characterized by an indolent course with a 4-year follow-up, and its association with quiescent rheumatoid arthritis (RA).
We report the case of a 85-year old French white man followed for quiescent anti-CCP+ rheumatoid arthritis treated by prednisolone 4 mg/day and hydroxychloroquine 200 mg/day since 10 years, and a monoclonal gammopathy of undetermined significance for 6 years, who was hospitalized for costal fractures after a fall. Serum protein electrophoresis showed a stable small monoclonal peak, and capillary electrophoresis/immunosubtraction technique identified an isolated clonal γ-heavy chain (HC). Bone marrow aspiration was normal and he had no other lymphoproliferation. The monoclonal peak remained stable after 4 years of follow-up.
In case of monoclonal peak without complete monoclonal Ig on serum protein electrophoresis, the diagnosis of γ-HCD should be discussed and capillary electrophoresis/immune-subtraction is a mean to detect isolated monoclonal heavy chain (HC). Gamma-HC disease is rare, may be associated to RA, and may have an indolent course.
Aims:
To identify factors associated with vascular events in patients with giant cell arteritis (GCA).
Methods:
We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who ...all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis.
Results:
Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients (p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis (p = 0.04), aortitis (p = 0.01), particularly of the descending thoracic aorta (p = 0.03) and atheroma (p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery hazard ratio (HR): 10.46 (1.41–77.80), p = 0.02, stroke HR: 22.32 (3.69–135.05), p < 0.001, upper limb ischemia HR: 20.27 (2.05–200.12), p = 0.01, lower limb ischemia HR: 76.57 (2.89–2027.69), p = 0.009, aortic atheroma HR: 3.06 (1.06–8.82), p = 0.04 and aortitis of the descending thoracic aorta on CT-scan at diagnosis HR: 4.64 (1.56–13.75), p = 0.006 were independent predictive factors of a vascular event.
Conclusion:
In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.
Plain language summary
Risk factors for symptomatic vascular events in giant cell arteritis
This study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known.
We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis.
Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis.
Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months.
Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group.
Among 254 GCA patients, 39 experienced at least one vascular event during follow-up.
Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors.
Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors.
This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.
ObjectivesTo develop and evaluate a self-administered questionnaire (LUPIN) to assess SLE disease activity and lupus-relevant PROs.MethodsPatient representatives from a nationwide lupus association ...(AFL+) and lupus experts developed a self- administered questionnaire which included several domains of SLE perceived activity (figure 1) and the SF-36 quality of life questionnaire. Prior to a medical consultation, the patient filled the questionnaire which was sealed. Subsequently, the physician evaluated the patient (blindly of the patient responses) and filled patient characteristics, a physician global assessment (PhGA) and a SLEDAI-2K. The questionnaires were distributed to 31 centers of metropolitan France and overseas territories. Correlations between patient response in individual domains and physician assessment were evaluated using Spearman’s regression and p-values were adjusted for multiple testing using the Bonferroni method.Results325 questionnaires were analyzed at the time of the submission. The mean age was 44 (±14.4) years and 85,2% were women. The mean duration of disease was 12.7 (±9.42) years. Most patients had history of articular and cutaneous involvements (86.6% and 72.6%, respectively) and 34.4% of lupus nephritis. The mean SLEDAI was 3 (±3.70) and 67 (20.6%) patients had a clinical SLEDAI ≥ 4. The PhGA correlated moderately with the cSLEDAI (r = 0.52). As expected, there was a weak albeit statistically significant correlation between components of the LUPIN questionnaire and the SLEDAI/cSLEDAI and PhGA (r < 0.25 for all; figure 2). However, there were very good correlations between several components of the LUPIN questionnaire and several domains of the SF-36 (r = -0.68 for pain evaluation; r = -0.65 for physical activity evaluation; r = -0.60 for fatigue evaluation; p < 0.0001 for all).Abstract LBP2 Figure 1The LUPIN questionnaire (paper or electronic form)Abstract LBP2 Figure 2Spearman’s correlation matrix between components of the LUPIN questionnaire, the SF-36 questionnaire and the physician’s assessment of disease activity. Each value corresponds to the spearman r value, in bold when there is a statistically significant correlation after adjusting p-value for multiple testing using the Bonferroni method.ConclusionSeveral components of the LUPIN questionnaires have significant correlation with domains of the SF-36 quality of life questionnaire making LUPIN a patient-friendly tool to evaluate PROs now that it has been implemented on smartphones. As expected in a cross-sectional study, there were only weak correlations between domains of the LUPIN questionnaire and physician-assessed disease activity. However, the changes in LUPIN scores assessed prospectively may be more sensitive to detect disease activity fluctuation, which is currently evaluated in a follow-up study.AcknowledgmentsAll patients and physicians who participated in the study. The AFL+ patient association represented by her president Marianne Riviere.
BackgroundVascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection.ObjectivesTo explore risk ...factors for a vascular phenotype of SSc, among them a history of pre-eclampsia.MethodsThis observational multicentre case–control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire.Results378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype.ConclusionsIn women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype.
Abstract Objectives Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and ...quality of life in SSc patients receiving bosentan. Methods ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI), pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. Results Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 ( p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 ( p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 ( p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 ( p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI ( p = 0.04), CHFS ( p = 0.04), and pain score ( p = 0.046). Conclusions In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.
Objectives Q fever is a worldwide zoonosis caused by Coxiella burnetii . Its presentation can be atypical, delaying and complicating the diagnosis. We report 7 cases of Q fever mimicking vasculitis, ...systemic inflammatory disease, or auto-immune disorder. Methods Seven cases of Q fever diagnosed between 1995 and 2007 in Nantes University Hospital (France) are described. They occurred in a nonendemic region and were selected on the basis of initial clinical presentation suggesting systemic immune disease. C. burnetii was detected using indirect immunofluorescence serology. Results Q fever was acute in 4 of the 7 patients and chronic in 3. None had endocarditis. The initial presentations suggested Crohn's disease, Goodpasture's syndrome, polymyalgia rheumatica, adult-onset Still's disease, polyarteritis nodosa, giant-cell arteritis, and essential type II cryoglobulinemia. Two patients had antiphospholipid antibodies, 1 had transient IgG kappa monoclonal gammopathy, and 1 had polyclonal T CD8+ large granular lymphocyte expansion. Conclusion Clinicians must be aware of the potential diagnosis of Q fever, and C. burnetii serology is a helpful diagnostic tool in the investigation of fever of unknown origin with atypical systemic symptoms suggesting vasculitis or inflammatory disease.
Objective
The prevalence of the involvement of large vessels in giant cell arteritis (GCA) is 3–13%. Aortitis is the most serious complication of GCA. Computed tomodensitometric (CT) scan allows ...analysis of both the aortic wall and endoluminal part of the aorta. Therefore, we conducted a study using CT scan to analyze aortic abnormalities in patients with recent‐onset GCA.
Methods
This prospective controlled study compared patients with biopsy‐proven GCA with a matched control group based on sex, age, and cardiovascular risk factors. During the 4‐week period following diagnosis of GCA, patients underwent an aortic CT scan. The aortic imaging results were blindly compared between both groups.
Results
From January 5, 1998 to January 11, 1999, 22 patients and 22 controls were screened by CT scan for aortic involvement. Thickening of the aortic wall was more frequent among patients than controls (45.4% versus 13.6%; P = 0.02). Aortic thickening (mean 3.3 mm) was located on the ascending part of the thoracic aorta in 22.7% of the patients, with no evidence of thickening in the controls (P = 0.05). Thickening of the abdominal aortic wall was noted in 27.3% of the patients and none of the controls (P = 0.02).
Conclusion
This study suggests that inflammatory aortic thickening, detected by CT scan, occurs frequently at the time of diagnosis of GCA, and that this condition predominantly occurs on the ascending part of the aorta.
PDF
