The functional disabilities of the dominant and opposite hands in patients with systemic sclerosis.

OBJECTIVES: Hand involvement in patients with systemic sclerosis (SSc) is responsible for 75% of the overall disability but varies greatly among individuals. No study has yet compared the functionalities between the two hands of SSc patients. We thus evaluated the joint limitations and extent of skin involvement in the dominant and contralateral hands. METHODS: This prospective, descriptive, comparative single-centre study enrolled SSc patients diagnosed using the ACR/EULAR criteria. We assessed limitations in the joint range of motion during active and passive mobilisation; the first commissure opening angles; the Kapandji scale and Rodnan hand scores; the digital pressures; the finger brachial pressure indices; and the number of telangiectasias, calcinosis, digital ulcerations, and painful joints on each hand. RESULTS: Thirty patients were included. Spontaneous flexion joint limitations were significantly greater in the dominant hand (p<0.0001). The Kapandji score was lower (p<0.001) and the Rodnan hand score significantly higher, for the dominant hand (p<0.001). The digital pressure was similar between the hands. CONCLUSIONS: The dominant hand exhibited significantly more skin sclerosis and mean flexion deterioration, a lower Kapandji score, and a tendency toward reduced mean extension, compared with the other hand. No vascular pathology was noted in either hand. Larger studies are needed to confirm these results and to draw therapeutic conclusions.

Upper respiratory tract and orofacial manifestations of new-onset giant cell arteritis: results from a large, prospective inception cohort study.

OBJECTIVES: Giant cell arteritis (GCA) often features upper respiratory tract (URT) and orofacial manifestations, which signal the involvement of external carotid artery branches. In this study, we aimed to describe the frequency of various URT/orofacial symptoms at GCA onset, as well as the main characteristics of patients presenting these symptoms. METHODS: We included all patients who were newly diagnosed with GCA between 1976 and April 2022 at the Internal Medicine Department of a tertiary-care hospital. Ten URT or orofacial symptoms were prospectively examined systematically in each patient. We used multivariate analyses to identify the GCA characteristics, including URT/orofacial symptoms, associated with temporal artery biopsy (TAB) positivity. RESULTS: At least 1 URT/orofacial symptom was present in 68.6% of the 599 patients (3 or more symptoms in 30% of cases). Jaw claudication, maxillary pain, and pain during mouth opening were the most prevalent symptoms. Dry cough was recorded in 17% of cases. GCA patients with URT/orofacial symptoms had more clinical abnormalities of the temporal artery bed and ischaemic ophthalmological complications, but less large-vessel vasculitis according to imaging. The likelihood of a positive TAB was increased in patients with an abnormal temporal artery upon clinical examination (OR 4.16; CI 2.75-6.37, p < 0.001) or jaw claudication (OR 2.18; CI 1.35-3.65, p = 0.002), and decreased in those with hoarseness (OR 0.47; CI 0.26-0.87, p = 0.02) or earache (OR 0.54; CI 0.31-0.95, p = 0.03). Isolated URT/orofacial presentation (i.e., without headache or visual signs) accounted for 5.2% of the entire cohort. CONCLUSIONS: Oral-facial symptoms were present in two-thirds of GCS cases. Thus, they could serve as leading clinical clues for a GCA diagnosis, and are a risk factor for permanent visual loss. Several URT/orofacial symptoms such as jaw claudication, hoarseness, and earache influenced the likelihood of a positive TAB. Isolated URT/orofacial presentation of GCA is a rare but potentially challenging occurrence.

Mouth opening in systemic sclerosis: A longitudinal analysis from the French National Cohort Study.

BACKGROUND: Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories. OBJECTIVE: To study MO trajectories in SSc. METHODS: This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modeled MO trajectories, and associated MO measures with SSc prognosis. RESULTS: We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan-Meier analysis, MO < 30 mm was associated with worse 30-year-survival (p<0.01) and risk of pulmonary arterial hypertension (p<0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent-process mixed modeling showed that 88.8% patients had a stable MO trajectory and clustered patients into 3 groups that predicted SSc survival (p<0.05) and interstitial lung disease (ILD) occurrence (p<0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p<0.05) and high but decreasing MO over 1 year (p<0.0001) who were at increased risk of poor survival and ILD. CONCLUSION: MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. This article is protected by copyright. All rights reserved.

Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension.

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Portopulmonary hypertension in the current era of pulmonary hypertension management.

BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function.

BACKGROUND: Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. METHODS: 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. RESULTS: Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P < 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes, P < 0.001; %H2: 56.0 % vs. 81.5 %, P < 0.001; %H4: 15.0 % vs. 57.5 %, P = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % (P = 0.04; 95 % confidence interval 0.51 - 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm2/mmHg. CONCLUSION: G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.

Contribution of dot-blot assay to the diagnosis and management of myositis: a three-year practice at a university hospital centre.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases with wide clinical spectrum that may lead to delayed diagnosis. The aim of this study was to examine the impact of IIM-specific dot-blot assay on diagnostic process of patients presenting with muscular or systemic symptoms evocating of IIM. METHODS: We collected all the prescriptions of an IIM specific dot-blot assay (8 autoantigens including Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, PM/Scl and Scl-70) over a 38-month period. RESULTS: 316 myositis dot-blot assays (MSD) were performed in 274 patients (156 women, mean age 53±10.6 years) referring for muscular and/or systemic symptoms suggesting IIM. The timing of dot prescription through the diagnostic process was highly variable: without (35%), concomitantly (16%) or after electromyographic studies (35%). Fifty-nine patients (22%) had IIM according to Bohan and Peter's criteria. Among them, 29 (49%) had positive dot (8 Jo-1, 6 PM-Scl, 5 PL-12, 5 SRP, 2 Mi-2, 2 PL-7 and 1 Ku). Various other diagnoses were performed including 35 autoimmune disease or granulomatosis (12%), 19 inflammatory rheumatic disease (7%), 16 non inflammatory muscular disorders (6%), 10 drug-induced myalgia (4%), 11 infectious myositis (4%). Except 11 borderline SRP results and one transient PM-Scl, MSD was positive only in one case of IIM. Dot allowed clinicians to correct diagnosis in 4 cases and improved the diagnosis of IIM subtypes in 4 cases. CONCLUSIONS: This study reflects the interest of myositis dot in the rapid diagnosis process of patients with non-specific muscular symptoms leading to various diagnoses including IIM.

Use of Complementary and Alternative Medicine by Patients Treated for Systemic Lupus Erythematosus, Primary Sjögren's Syndrome, or Systemic Sclerosis in a French Rural Region.

BACKGROUND: Complementary and alternative medicine (CAM) is composed of a wide range of interventions and frequently used in parallel with conventional medicine. The aim of this study was to assess the prevalence, modalities, and association factors of CAM utilization in patients treated for systemic lupus erythematosus, primary Sjögren's syndrome, or systemic sclerosis. PATIENTS AND METHODS: This was a prospective single-center observational study conducted in a French university hospital center. Inclusion criteria were patients followed for systemic lupus erythematosus, primary Sjögren's syndrome, or systemic sclerosis. Data were collected with a survey which assessed sociodemographic, disease characteristics, CAM use details, life quality, and anxiety score. RESULTS: A total of 121 patients were included, mostly women (87%), with an average age of 56 years. Proportion of patients seeking CAM was 55%. A total of 186 CAM interventions were recorded: most common were osteopathy, homeopathy, and acupuncture. Patients were looking for well-being (22%), reducing their fatigue (18%) and pain (33%). Concerning physical and mental feeling after CAM use, a subjective improvement was reported in 89% of cases. In multivariate analysis, CAM use by patient was associated with these 3 variables: coming from a Western culture, being professionally active, and having a poor quality of life and anxiety scores. CONCLUSION AND OUTLOOK: This is the first study to focus on CAM use in patients followed for three AID in a French rural region. The current challenge is to enrich conventional medicine with CAM that is effective and safe through supervised programs to move toward an integrative medicine.Die Komplementär- und Alternativmedizin (CAM) umfasst ein breites Spektrum an Interventionen und wird häufig parallel zur konventionellen Medizin angewendet. Das Ziel dieser Studie war die Beurteilung der Prävalenz, Modalitäten und Assoziationsfaktoren der CAM-Anwendung bei Patienten, die wegen systemischem Lupus erythematodes, primärem Sjögren-Syndrom oder systemischer Sklerose behandelt werden.Es handelte sich um eine prospektive monozentrische Beobachtungsstudie, die an einem französischen Universitätsklinikum durchgeführt wurde. Eingeschlossen wurden Patienten, die dort wegen systemischem Lupus erythematodes, primärem Sjögren-Syndrom oder systemischer Sklerose in Behandlung waren. Die Datenerhebung erfolgte mittels eines Fragebogens, der soziodemografische Merkmale, Krankheitsmerkmale, Einzelheiten der CAM-Anwendung, Lebensqualität- und Angst-Scores umfasste.Insgesamt wurden 121 Patienten randomisiert, überwiegend Frauen (87%); das Durchschnittsalter betrug 56 Jahre. Der Anteil der Patienten, die CAM wünschten, betrug 55%. Insgesamt 186 CAM-Interventionen wurden erfasst; am häufigsten Osteopathie, Homöopathie und Akupunktur. Den Patienten ging es dabei um das Wohlbefinden (22%) sowie die Linderung von Müdigkeit (18%) und Schmerzen (33%). Hinsichtlich des physischen und psychischen Befindens nach der CAM-Anwendung berichteten 89% der Befragten über eine subjektiv empfundene Verbesserung. In multivariaten Analysen war die CAM-Anwendung pro Patient mit den folgenden 3 Variablen assoziiert: aus einer westlichen Kultur stammend, berufstätig sowie schlechte Lebensqualität- und Angst-Scores.Dies ist die erste Studie zur CAM-Anwendung bei Patienten, die im ländlichen Raum in Frankreich wegen einer von drei Autoimmunerkrankungen behandelt werden. Die aktuelle Herausforderung lautet, der konventionellen Medizin in supervidierten Programmen wirksame und sichere CAM-Interventionen an die Seite zu stellen, um zu einer integrativen Medizin zu gelangen.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

Frequency and Significance of Hepatic Involvement in New-Onset Giant Cell Arteritis: A Study of 514 Patients.

Abnormalities of liver function in giant cell arteritis (GCA) have long been described1 and are present at the acute phase of the disease in 30% to 60% of cases.2-4 Hepatic involvement is mostly anicteric cholestasis (eg, elevated alkaline phosphatase [ALP] and gamma-glutamyl transferase [GGT]), and, more rarely, cytolytic hepatitis (eg, elevated aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]).

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Giant cell arteritis-related stroke in a large inception cohort: A comparative study.

OBJECTIVE: Stroke caused by giant cell arteritis (GCA) is a rare but devastating condition and early recognition is of critical importance. The features of GCA-related stroke were compared with those of GCA without stroke and atherosclerosis-related or embolic stroke with the aim of more readily diagnosing GCA. METHODS: The study group consisted of 19 patients who experienced GCA-related strokes within an inception cohort (1982-2021) of GCA from the internal medicine department, and the control groups each consisted of 541 GCA patients without a stroke and 40 consecutive patients > 50 years of age with usual first ever stroke from the neurology department of a French university hospital. Clinical, laboratory, and imaging findings associated with GCA related-stroke were determined using logistic regression analyses. Early survival curves were estimated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Amongst 560 patients included in the inception cohort, 19 (3.4%) developed GCA-related stroke. GCA-related stroke patients had more comorbid conditions (p = 0.03) and aortitis on imaging (p = 0.02), but less headache (p < 0.01) and scalp tenderness (p = 0.01). Multivariate logistic regression analysis showed that absence of involvement of the anterior circulation (OR = 0.1 - CI: 0.01-0.5), external carotid ultrasound (ECU) abnormalities (OR = 8.1 - CI: 1.3-73.9), and C-reactive protein (CRP) levels > 3 mg/dL (OR = 15.4 - CI: 1.9-197.1) were independently associated with GCA-related stroke. Early survival of GCA-related stroke patients was significantly decreased compared with control stroke patients (p = 0.02) and GCA patients without stroke (p < 0.001). CONCLUSIONS: The location of stroke and assessment of ECU results and CRP level could help improve the prognosis of GCA-related stroke by bringing this condition to the clinician's attention more quickly, thus shortening diagnostic delay.

Comparison between idiopathic and VEXAS-relapsing polychondritis: analysis of a French case series of 95 patients.

OBJECTIVE: A new adult-onset autoinflammatory syndrome has been described, named VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic). We aimed to compare the clinical characteristics, the laboratory features and the outcomes between idiopathic-relapsing polychondritis (I-RP) and VEXAS-relapsing polychondritis (VEXAS-RP). METHODS: Patients from French retrospective multicentre cohort of RP were separated into two groups: a VEXAS-RP and an I-RP. RESULTS: Compared with patients with I-RP (n=40), patients with VEXAS-RP (n=55) were men (96% vs 30%, p<0.001) and were older at diagnosis (66 vs 44 years, p<0.001). They had a greater prevalence of fever (60% vs 10%, p<0.001), of skin lesions (82% vs 20%, p<0.001), of ocular involvement (57% vs 28%, p=0.01), of pulmonary infiltrates (46% vs 0%, p<0.001), of heart involvement (11% vs 0%, p=0.0336) and with higher median C-reactive protein levels (64 mg/L vs 10 mg/L, p<0.001). Seventy-five per cent of the patients with VEXAS-RP had myelodysplastic syndrome (MDS) versus none in I-RP group. The glucocorticoids use, and the number of steroid sparing agents were similar in both groups, but patients with VEXAS-RP had more frequent refractory disease (remission obtained in 27% vs 90%, p<0001). VEXAS-RP was associated with higher risk of death: six patients (11%) died in the VEXAS-RP group after a median follow-up of 37 months and none in the I-RP group after a median follow-up of 92 months (p<0.05). CONCLUSION: We report the largest cohort of VEXAS-RP, characterised by high prevalence of male sex, fever, skin lesion, ocular involvement, pulmonary infiltration, heart involvement, older age and MDS association.

Active immunological profile is associated with systemic Sjögren's syndrome.

BACKGROUND: The aim of this paper was to study the evolution of primary Sjögren's syndrome (pSS) immunological profile, its impact on pSS activity and long-term evolution in a bicentric cohort of French patients with pSS (n = 445, mean age 53.6 ± 14 years, mean follow-up 76.1 ± 51 months). METHODS: This is a retrospective cohort study. RESULTS: Two hundred twelve patients were Sjögren's syndrome A (SSA) positive, and 131 were both SSA and Sjögren's syndrome B (SSB) positive. Sixty-eight patients (15%) had cryoglobulinemia. Active systemic profile (i.e., hypergammaglobulinemia, rheumatoid factor (RF), and anti-Sjögren's syndrome A (anti-SSA), anti-Sjögren's syndrome B (anti-SSB) positivity), associated with multisystemic involvement, leads to an increased utilization of corticosteroid and hydroxychloroquine. Multivariate analysis pointed out independent statistical association between hypergammaglobulinemia, anti-SSA, anti-SSB, and RF. Cryoglobulinemia is associated with multi-systemic involvement, lymphoma, and pSS-related death. CONCLUSION: The subset of patients with active immunological profile is characterized by systemic complications leading to immunosuppressive drug utilization and polyclonal B-cell activation profile.

Abdominal symptoms during Sjogren's syndrome: a pilot study.

BACKGROUND: Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease. METHODS: One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected. RESULTS: Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each). CONCLUSIONS: The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms. TRIAL REGISTRATION: NCT03157011 . Date of registration: July 17, 2017.

Risk profiling for a refractory course of giant cell arteritis: The importance of age and body weight: "Risk profiling for GC resistance in GCA".

BACKGROUND: Giant cell arteritis (GCA) is a disease that relapses often, and some patients run a refractory course. Although prompt recognition of resistant GCA is a major issue, there is no well-recognized, baseline risk factor for poor response to glucocorticoid (GC) treatment. METHODS: We included all patients consecutively diagnosed with GCA and homogeneously treated since 1976 in a single department and regularly followed-up for at least 18 months. Using a set of customized criteria defining response to GCs, we separated patients into highly responsive, usually responsive, dependent on GCs, and resistant to GCs. We determined which of the baseline variables were associated with GC-resistance and conducted factor analyses of mixed data and decision tree analyses. We also determined whether being GC-resistant was associated with poorer tolerance to GCs and higher death rates. RESULTS: In all, 455 patients were followed for 93.4 ± 67.6 (standard deviation) months; 41 (9%) and 21 (4.6%) patients developed GC-dependent and GC-resistant disease, respectively. Factor analyses suggested an association between clinical pattern and degree of responsiveness to GCs; The decision tree analyses, built on an age at GCA onset 〈 66 years and body weight 〉 71 kg, delineated a high risk profile (44% of the patients who featured both characteristics were GC-resistant vs. less than 3% who featured neither, p < 0.001). Infections were more prevalent in the GC-resistant or GC-dependent patients, but without decreasing their survival. CONCLUSION: Extra-cranial, large-vessel GCA may be associated with prolonged GC requirements. A simple combination of age and body weight defined a subgroup of patients at high risk for developing GC resistance. Our findings need confirmation in prospective controlled studies.

Venous thrombosis in patients with giant cell arteritis: Features and outcomes in a cohort study.

OBJECTIVES: To describe the features and outcomes of patients with giant cell arteritis who developed venous thrombosis. METHODS: Inception cohort study including 428 newly diagnosed patients of giant cell arteritis from 1976 to 2014. Clinical and biological data and outcomes were analysed by comparing patients with and without venous thrombosis. RESULTS: Twenty-six patients (6%) developed venous thrombosis, 12 of whom presented with pulmonary embolism. The mean time between the onset of giant cell arteritis symptoms and venous thrombosis occurrence was 248.8±215.0 days. No difference was observed between the two groups in clinical or laboratory data collected at diagnosis. The mean time from the start of prednisone to venous thrombosis diagnosis was 187.7±217.0 days. The average dose of prednisone at venous thrombosis onset was 21.5mg/day. The venous thrombosis group had a higher number of glucocorticoid-related adverse effects (mean, 3.1 vs 1.1; P<0.0001), a higher mortality rate (58% vs 33%, P=0.01) and a higher proportion of deaths occurring during glucocorticoid treatment (31% vs 14%, P=0.03). Death was related to venous thrombosis in four patients. DISCUSSION: The occurrence of overt venous thrombosis is more than anecdotal among patients treated for giant cell arteritis. Venous thrombosis does not rely on the active phase of giant cell arteritis, but could be associated with long-term use of glucocorticoids. Because venous thrombosis may be associated with an increased mortality risk in patients with giant cell arteritis, a high index of suspicion should be applied in appropriate settings, especially in patients experiencing multiple glucocorticoid-related adverse effects.

T Cell Polarization toward TH2/TFH2 and TH17/TFH17 in Patients with IgG4-Related Disease.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes' subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+ TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of TFH2 (CCR6-CXCR3-), and to a lesser extent of TFH17 (CCR6+CXCR3-) cells. Interestingly, CD4+CXCR5+PD1+ TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.

Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

OBJECTIVES: To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. METHODS: Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. RESULTS: Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. CONCLUSION: RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.