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Objectives: Sjögren's syndrome (SS) is an autoimmune disease with an impact on quality of life (QoL). The aim of patient education (PE) is to improve patients' QoL. The main objective of this study was to describe the medico-psycho-social characteristics defining the six spheres of an allosteric educational model in order to characterise clusters of patients with SS and intentionality for patients to participate in a programme of patient education., Methods: A self-administered questionnaire was proposed to 408 patients with SS followed in the Department of Internal Medicine of the University Hospital of Lille, France with the aim of assessing the six spheres of the allosteric model: intentional, perceptual, affective, cognitive, infra-cognitive and meta-cognitive. Sub objectives were to determine factors that can influence intentionality to participate in a PE programme and to determine, using cluster analysis, similar characteristics of patients with SS., Results: 127 patients (31%) agreed to participate and were included in the study; 96% were women and the median age was 51 years (±14.5). They mostly reported dry syndrome and fatigue, had a good knowledge of SS, and presented anxiety symptoms. They mainly had problem-centred coping strategies, internal locus of control and low self-esteem. SS had an impact on their social interactions. Considering intentionality to participate in a PE programme, the patients were significantly younger, had a shorter duration of the disease, more frequently had disabled status, reported more fatigue, more self-reported symptoms and a poorer QoL. Two clusters of patients could be individualised, with one group including 75 (59%) patients presenting a higher global impact of the disease, including a more severe impairment for the scores of the perceptual, emotional and infra-cognitive spheres, worse physical QoL, and a higher intentionality to participate in a PE programme., Conclusions: Our study described an SS population in terms of the different spheres of an allosteric model applicable to the practice of PE. A cluster of patients appeared to present more impact of the disease and more intentionality to participate in a programme of PE. There was no difference between the two groups in terms of the cognitive sphere (i.e. knowledge of the disease), thus indicating that motivation to participate in a PE programme is influenced by non-cognitive factors. Considering intentionality to participate in a PE programme, duration disease, age of the patient and QoL should be more considered to propose to patients to participate in a PE programme. Use of the allosteric model appears promising for future research in PE.

Objectives: Cryopyrin-associated periodic syndromes (CAPS) belongs to the group of hereditary recurrent fever disorders characterised by interleukin1β-mediated systemic inflammation. Specific treatment by IL-1 targeting drugs has significantly modified the disease evolution. We aimed to evaluate the socio-professional impact of CAPS in the long term and the influence of genetic variants in the phenotype., Methods: We made a multicentre, observational and descriptive study and collected retrospective data from childhood to adulthood, and until the last year of follow-up. We assessed the quality of life (QoL) of the patients by phone interviews. We also used the SF36 questionnaire including 8 domains: physical function, physical role, body pain, general health, vitality, social function, emotional role and mental health. A high score means a better QoL., Results: Fifty-four patients were evaluated (14 familial cold autoinflammatory syndrome, 27 Muckle-Wells syndrome, 7 chronic infantileneurological cutaneous and articular syndrome. The study showed improvement in symptoms in adulthood and good QoL in all domains apart from school (87%) and work (61%) absenteeism. The MWS group is intermediate in terms of symptoms but seems to describe a better QoL compared to the other groups. The genetic variant alone does not determine the expression of the disease., Conclusions: Our study shows that CAPS patients have an improvement of symptoms in adulthood and a satisfactory QoL for most of them. Anti-IL1 treatment is the main factor linked to this improvement and therefore early initiation should be encouraged.

Objectives: To evaluate whether inflammatory and complement biomarkers are associated with specific characteristics of antiphospholipid syndrome (APS)., Methods: Serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, interferon-α (IFN)-α, IFN-γ, vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule (VCAM)-1, and plasma levels of soluble C5b-9 (sC5b-9), C3a, C4a, Bb fragment were measured in unselected APS patients. Twenty-five healthy blood donors were included as controls., Results: Between January 2020 and April 2021, 98 APS patients were included outside acute thrombosis (median time from the last APS manifestation: 60 (23;132) months). Levels of IL6, VCAM-1, sC5b-9, C3a, C4a, and Bb were significantly increased in APS patients compared to controls. A cluster analysis allowed to divide patients into two clusters: "inflammatory" (higher levels of IL-6 and VCAM-1) and "complement". In APS, elevated IL-6 was associated with hypertension, diabetes, BMI, and hypertriglyceridaemia. 85% of our APS patients had elevated levels of at least one complement biomarker. Elevated Bb (34%) was associated with aPL positivities, especially with triple aPL positivity (50% vs. 18%, p<0.001). 7/8 patients with history of catastrophic APS had elevated levels of complement biomarkers., Conclusions: Our findings suggested that APS patients outside acute thrombosis might be divided into two clusters: "inflammatory" and "complement". Elevated IL-6 was associated with cardiovascular risk factors and metabolic parameters, whereas Bb fragments, a marker of alternative pathway complement activation, was strongly associated with aPL profile at highest risk of severe disease.

Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE., Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders., Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83)., Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Objectives: We aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs)., Methods: A survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy., Results: Twelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF., Conclusions: MMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.

Objectives: Gender can influence incidence and clinical course of autoimmune diseases (ADs). Antiphospholipid syndrome (APS) is a rare AD characterised by thromboses and/or pregnancy morbidities and antiphospholipid antibodies (aPL) positivity. Our aim is to conduct a gender-oriented analysis of primary thrombotic APS (t-APS)., Methods: Consecutive patients diagnosed with primary t-APS, followed from 1967 to 2019 in four European Centres, were enrolled., Results: The cohort included 296 women and 137 men. Median age at onset [31 (24-46) vs. 41 (29-53) years, p<0.001] was lower in females. In women, venous thromboses were more frequent while, among males, arterial events prevailed. During follow-up, 14% of patients suffered at least two relapses and this occurred especially among males (22% vs. 10%, p=0.001). No gender differences were found in the aPL profile (33% single, 24% double and 43% triple aPL positivity). Most patients had concomitant risk factors (RFs) for thrombosis: established cardiovascular RFs were represented especially among men while estrogenic exposure was the main RF in women., Conclusions: Women presented mostly with venous thromboses at a younger age, while men with arterial events, later in life and suffered more recurrent events. This different frequency of arterial and venous thromboses could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, some RFs are exclusive or more represented in one gender rather than the other, so assessing the link of causality between gender and manifestations of t-APS remains difficult.

Sjögren's syndrome (SS) is a systemic autoimmune disease that frequently occurs concomitantly with other systemic connective tissue disorders, including rare and complex diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The presence of SS influences the clinical expression of the other autoimmune diseases, thus offering the unique opportunity to explore the similarities in genetic signatures, as well as common environmental and biologic factors modulating the expression of disease phenotypes. In this review, we will specifically discuss the possibility of defining "SS/SLE" and "SS/SSc" as distinct subsets within the context of connective tissue diseases with different clinical expression and outcomes, thus deserving an individualised assessment and personalised medical interventions.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a chronic, clinically heterogenous fibroinflammatory condition, characterised by an accumulation of IgG4 secreting plasma cells in affected tissues and associated with increased serum IgG4 concentrations. Despite a growing recognition of the disease among clinicians from different specialties worldwide, its indolent nature, lack of a single diagnostic test and ability to mimic other malignant, infective and inflammatory conditions, makes the diagnosis challenging. As treatment options evolve, biomarkers correlating with disease activity, predicting prognosis and response to treatment are deemed required. A multidisciplinary panel of experts from the European Reference Network for Rare and Complex Connective tissue diseases (ERN ReCONNET) and affiliated international partners have performed a narrative literature search and reviewed the current evidence of biomarkers in IgG4-RD, including immunoglobulins, cytokines, chemokines and other soluble immune mediators, and cellular components of the immune system. The aim of this paper is to provide useful information for clinicians as to the utility of biomarkers for diagnosing and monitoring IgG4-RD in clinical routine and sets out recommendations for clinical decision making.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

Objectives: Dryness, fatigue, and pain are classic symptoms in primary Sjögren's syndrome (pSS) but are also common in fibromyalgia (FM). We compared the characteristics of FM assessed by different criteria (American College of Rheumatology (ACR) 2016 and 1990 criteria), physician's opinion and Fibromyalgia Rapid Screening Tool (FiRST) questionnaire) in a cohort of patients with pSS., Methods: Eight hospital departments tested 134 patients with pSS according to AECG criteria from the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort., Resuklts: FM was present in 19%, 18%, 20%, and 29% of cases according to ACR 2016, ACR 1990 criteria, physician's opinion and the FiRST questionnaire, respectively. FM criteria-positive patients had higher EULAR SS Patient-Reported Index (ESSPRI) score, but not higher EULAR SS Disease Activity Index (ESSDAI) score. The objective measurements of dryness and the use of corticosteroids and immunosuppressive drugs did not differ between FM positive and negative patients. Regarding the ESSPRI dryness and fatigue subscale scores, depression and anxiety scores and the use of anxiolytics and antidepressants, the FiRST questionnaire exhibited a higher difference between positive and negative patients than ACR 2016 criteria. ACR 1990 and physician's opinion were somewhere in the middle. ACR 2016 exhibited moderate agreement with ACR 1990 (κ=0.52) and the physician's opinion (κ=0.60) and poor agreement with FiRST (κ=0.39)., Conclusions: The FM criteria identified pSS patients with higher ESSPRI scores but not higher ESSDAI systemic disease scores. Agreement between the different FM criteria was moderate, and the characteristics they described did not fully coincide.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune multi-organ disease with an unpredictable course. SLE causes functional disability, changes in body appearance, and psychological distress. When faced with SLE, patients have to implement coping strategies. Therefore, the aim of this study was to describe patients' coping strategies, consider the implications for a personalised practice of patient education and evaluate patients' adherence to HCQ treatment., Methods: One hundred and fifty-eight SLE patients receiving hydroxychloroquine (HCQ) treatment entered a prospective, non-comparative, longitudinal study aimed at describing patients' coping strategies and evaluating their adherence to the HCQ regimen. Coping strategies were evaluated using an abbreviated French version of the WCC-27 exploring 3 dimensions of coping: problem-centered coping, emotion-centered coping and search for social support. Adherence was assessed by the MASRI, the MMAS-8 and also objectively assessed by the patient's serum level of HCQ. Data collected at study entry also included disease activity: SLEDAI, and disease extent: SLICC damage index. The prevalence of anxious and depressive symptoms was evaluated with the HADS. Quality of life was evaluated using the LupusQoL questionnaire., Results: Patients were clustered using an unsupervised hierarchical classification based on coping strategies. Four clusters of patients were individualised. The cluster of patients with low problem-centered coping, high emotion-centered coping and the lowest search for social support had worse quality of life and more psychological distress. We did not find any inter-cluster differences in terms of compliance to HCQ., Conclusions: Patients' knowledge is not the only parameter to consider for a personalised educational therapy: psychological parameters such as coping must also be considered to ensure the best possible quality of life. For educational therapy purposes, it is important not to group patients with the same coping style; heterogenous groups will enable patients to share their experiences and learn from the coping strategies of others.

Objectives: To evaluate the diagnostic value of hand ultrasound (US) in systemic sclerosis (SSc) and to explore its relevance within a combined diagnostic approach., Methods: 224 patients with suspected SSc were consecutively included. They all had US evaluation assessing the presence of fibrotic tenosynovitis (fibrotic TS) and ulnar artery occlusion (UAO). The final diagnosis of SSc was based on the clinical evaluation of a board of experts independently of any pre-established classification criteria., Results: 166 patients were finally diagnosed as SSc according to the experts as reference standard. 62 SSc and 8 non-SSc patients had UAO (uni or bilateral) (p=0.001). 23 SSc patients and 1 non-SSc patient had US fibrotic TS (p=0.007). A US SSc-pattern (presence of UAO and/or fibrotic TS) was reported in 73 SSc patients and 9 non-SSc patients (p<0.001). UAO had an area under ROC curve (AUC) for the diagnosis of SSc of 0.618 (95%CI 0.539- 0.697); with Se=0.373 (0.304-0.449) and Sp=0.862 (0.751-0.928). Fibrotic TS had an AUC of 0.561 (0.480-0.643); with Se=0.139 (0.094-0.199) and Sp=0.983 (0.909-0.997). The US-SSc pattern had a AUC of 0.641 (0.563- 0.695), with Se=0.440 (0.367-0.516) and Sp=0.845 (0.731-0.916). A scoring system including these US parameters and items from ACR/EULAR classification criteria had an AUC of 0.979 (0.962-0.996)) and allows the substitution of capillaroscopy by US parameters with similar performances., Conclusions: The use of hand US parameters may help to refine the diagnostic strategy of SSc and their inclusion in a combined diagnostic approach could be discussed.

Objectives: Retroperitoneal fibrosis (RPF) is a rare disease, with unknown aetiology (idiopathic RPF: iRPF) in two-thirds of cases. A subset of iRPF may be a manifestation of IgG4-related disease (IgG4-RD). Thus, recognition of IgG4-RD-RPF is crucial to optimise patient's care with iRPF. The current study aimed to examine imaging specific patterns, which could help differentiate between IgG4-RD-RPF and iRPF, and thus skip performing biopsies., Methods: This analysis included patients with iRPF and a retroperitoneal biopsy at the Lille University Hospital, France. We reviewed their baseline characteristics, clinical presentation, biological results and imaging features. Patients were classified in 3 groups according to histopathological characteristics of IgG4-RD as follows: highly suggestive of IgG4-RD, possible IgG4-RD, or non-evocative of IgG4-RD., Results: Of the 18 patients analysed in the study, 4 (22%) patients had highly suggestive IgG4-RD-RPF, 8 (44%) possible IgG4-RD-RPF and 6 (33%) non-evocative IgG4-RD. We found no clinical, biological features nor specific imaging pattern that could help differentiate between the 3 groups., Conclusions: After ruling out all known causes of RPF, retroperitoneal biopsy is still necessary to ascertain the diagnosis of IgG4-RD-RPF. No specific pattern can be used to distinguish between IgG4-RD-RPF and iRFP.

Objectives: Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS)., Methods: Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools., Results: FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM., Conclusions: The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.

Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc., Methods: Two SNPs of CD2, rs624988 and rs798036, were genotyped in a total of 1,786 SSc patients and 2,360 healthy individuals from two European populations (France and Italy). Meta-analyses were performed to assess whether an association exists between CD2 polymorphisms or haplotypes and SSc or its main subtypes., Results: The combined analyses revealed an association between the rs624988 A allele and SSc susceptibility: padj=0.023, OR=1.14 (95%CI 1.04-1.25). Single marker analysis did not reveal any association between rs798036 and SSc. Haplotype analysis identified that the A-T haplotype, previously described in RA, was associated with higher susceptibility for SSc (padj=0.029, OR=1.14, 95%CI 1.04-1.25) and with the positive anti-centromere antibody sub-group of SSc patients (padj=0.009, OR=1.19 95%CI 1.07-1.32). Genotype-mRNA expression correlations revealed that the CD2 risk haplotype was associated with decreased CD2 mRNA expression in SSc patients., Conclusions: Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and RA.

Objectives: To evaluate the efficacy of rituximab in central nervous system (CNS) manifestations of patients with primary Sjögren's syndrome (pSS)., Methods: Prospective data from patients with pSS and CNS involvement included in the French AutoImmunity and Rituximab registry were analysed. All patients had diffuse white matter T2-weigted hypersignals. Neurological response was defined as improvement or disappearance of neurological signs., Results: Eleven patients (mean age 55 years [38-77]) were treated with rituximab for their neurological involvement. The mean duration of pSS was 9 years (4-24). Mean baseline ESSDAI score was 17 (5-25). Neurological features were progressive multiple sclerosis-like manifestations (n=6), transverse myelitis (n=1), anxiety and depression disorder (n=1) and cognitive dysfunction (n=3). Mean Expanded Disability Status Score (EDSS) before rituximab was 4 (3-5.5). The mean follow-up was of 13 months (6-58). No neurological change occurred in all 6 patients with multiple sclerosis-like symptoms, in 2/3 patients with cognitive dysfunction or in the patient with anxiety-depression. One patient with depression and cognitive dysfunction disclosed subjective improvement. One patient with transverse myelitis, refractory to cyclophosphamide had an improvement of his walk perimeter (160 meters vs. 116). Mean EDSS score and ESSDAI remained stable., Conclusions: Rituximab does not seem to be effective in progressive multiple sclerosis-like manifestations of patients with pSS-related CNS involvement.

Background: BANK1 and BLK B-cell genetic markers have been reproducibly and convincingly found to contribute to susceptibility to systemic sclerosis (SSc)., Objectives: To determine whether other B-cell genetic markers including CD19, CD20, CD22 and CD24 polymorphisms affect susceptibility to SSc in the European Caucasian population., Methods: A case-control study was performed in 900 patients with SSc and 1034 healthy controls. Among the whole SSc population, 304 (34%) had the diffuse cutaneous subtype, 551 (61%) had the limited cutaneous subtype, 732 (81%) were positive for antinuclear antibodies , 331 (37%) were positive for anticentromere antibodies and 228 (25%) for the topo-isomerase I. Genotyping has been performed for CD19 rs35979293, CD19 rs2904880, CD20 rs7126354, CD20 rs3802954, CD20 rs105146, CD20 rs4939364, CD22 rs10406069, CD22 rs10413500, CD22 rs10419538, CD22 rs34826052 and CD24 ins-del polymorphisms., Results: Genotype frequencies were at the Hardy-Weinberg equilibrium in the control population for all the SNPs investigated and observed frequencies were very similar to those expected in the European population. Allelic and genotypic frequencies for all these tested SNPs were found to be similar in SSc patients and controls. Moreover, subphenotype analyses in particular for subgroups having the diffuse cutaneous subset or topo-isomerase I positive antibodies, which are the most associated with BANK1 variants, did not detect any difference between SSc patients and controls., Conclusions: These results obtained through a large cohort of European caucasian patients with SSc do not support the contribution of CD19, CD20, CD22, CD24 variants to the genetic susceptibility of SSc.

Introduction: Accumulating evidences show that shared autoimmunity is critical for the pathogenesis of many inflammatory rheumatic conditions. Specific phenotype could arise from specific genes, and/or combination of genetic factors and environment. Systemic sclerosis (SSc) belongs to connective tissue disorders and recent data have highlighted strong associations with some autoimmunity genes shared with other autoimmune diseases., Objectives: To determine whether novel risk loci associated with rheumatoid arthritis (RA) may confer susceptibility to SSc. Single nucleotide polymorphism from CCL21, CD244 and CDK6 were tested for association., Methods: SNPs harbouring association with RA, CCL21-rs2812378, CDK6-rs42041 and CD244-rs6682654 were genotyped in a cohort of 1031 SSc patients and 1014 controls. All individuals were of European Caucasian origin., Results: The three polymorphisms were in Hardy-Weinberg equilibrium in the control population and allelic frequencies were similar to those expected in European populations. Allelic and genotypic frequencies for these three polymorphisms were found to be similar in SSc patients and controls. Moreover, sub-phenotype analyses in particular for subgroups having diffuse subcutaneous subtype, specific auto-antibodies or fibrosing alveolitis did not detect any difference between SSc patients and controls., Conclusions: These results obtained through a large cohort of European Caucasian SSc patients do not support the implication of CCL21, CD244 and CDK6 genes in the pathogenesis of SSc although these genes were recently identified as RA susceptibility genes.

We describe the case of a patient with a two-year history of adult dermatomyositis (DM) who developed malabsorption revealing celiac disease. Our observation raises the question of an association between DM and celiac disease as part of a continuum, suggesting that celiac disease may be included within the spectrum of the gastrointestinal manifestations of DM and polymyositis (PM). From a practical point of view, our data indicate that the diagnosis of celiac disease should be suspected in PM/DM patients exhibiting malabsorption syndrome. Based on our findings, we further emphasize that an evaluation for celiac disease, including anti-gliadin antibodies, anti-endomysium antibody and tissue trans-glutaminase antibodies should be considered in PM/DM patients presenting with unusual and unexplained gastrointestinal features. This could lead to the early management of such patients, resulting in decreased morbidity (i.e., malnutrition and malignancy) related to misdiagnosed celiac disease.

Objective: Survival in patients with giant cell arteritis (GCA) has generally been found to be similar to that of the general population. The aim of our study was to assess outcome and survival of different subgroups of patients with GCA in relation to clinical, biological data or treatment modalities., Methods: From 1977 and 1995, 176 patients were treated in the Department of Internal Medicine for GCA. The patient, family or local practitioner were contacted prior to the study (July-October 1995). Treatment modalities and follow-up were obtained for 133 patients. All patients (except 11) had 3 or more 1990 ACR classification criteria for GCA. The 11 patients with 2 criteria had a positive temporal biopsy and were included in the study., Results: Relapse during corticosteroid tapering treatment was observed in 83 patients (62.4%) with a mean 1.57 relapses per patient. No correlation was found in age, sex, initial dose or type of steroid used (i.e. prednisone or prednisolone). Only a slight correlation in the initial erythrocyte sedimentation rate (ESR) was observed (p < 0.01, r = 0.23). In 56 patients free of treatment (mean treatment duration: 40 months), 27 (48%) developed a relapse of the disease 1 to 25 months later. No correlation was found in age, sex, initial dose of steroid, number of relapses during treatment, or initial ESR. Survival analysis was performed using the Kaplan-Meier and Mantel-Menszel methods for comparison of groups. At the time of the study, 41 patients had died (30.7%). A significant reduction of survival was found with the presence of permanent visual loss vs absence (p = 0.04), in patients who required more than 10 mg/d of glucocorticoid (p < 0.001) at 6 months treatment and in patients treated with prednisone (vs prednisolone) (p < 0.01). However, these factors were not independently associated with survival in the multivariate analysis., Conclusion: Relapse was observed in 62.4% of the patients during corticosteroid tapering (correlated with initial ESR). A relapse of the disease was also observed in 48% of patients 1 to 25 months after the end of the treatment and was associated with prednisolone use. Long term survival was better in patients with no initial ocular manifestations, in patients who took less than 10 mg/day of corticosteroids at 6 months of the treatment and in patients treated with prednisolone.

Combining cyclophosphamide (Cy) and corticosteroids has dramatically improved the prognosis of Wegener's granulomatosis (WG). But this treatment carries the risks of severe infectious complications and drug toxicity. During a 10-month period, we observed 6 cases of Pneumocystis carinii pneumonia (PCP) in 23 patients with biopsy-proven WG and renal involvement. These 23 patients were enrolled in a multicenter controlled clinical trial designed to evaluate the efficacy and safety of either intermittent high-dose pulse Cy or daily oral low-dose Cy in combination with oral prednisone. Mean delay of onset of PCP was 2.5 months after the beginning of the immunosuppressive therapy. In all cases, the diagnosis of PCP was established by cytological examination of bronchoalveolar lavage fluid. None of the patients experienced severe leukopenia at the time of diagnosis, but the mean lymphocyte count decreased to 495/mm3 (range 100 to 830/mm3) and 2 patients had inverted CD4/CD8 T-cell ratios. Renal function was significantly impaired (creatininemia = 493.5 vs 195.4 micromol/l; p = 0.03) in the 6 patients presenting PCP vs those without. High-dose co-trimoxazole therapy was successful in 3 patients, but 3 others who required mechanical ventilation died. Treatment of WG with daily prednisone and either pulse or oral Cy may have contributed to higher rates of PCP in the past than previously thought and, therefore, patients currently receiving such a regimen may be at greater risk for PCP. For these patients, this opportunistic infection must remain highly suspect in order to reach a diagnosis earlier and rapidly initiate treatment. In addition, recommendations for prophylactic therapy are needed.

A prospective clinical study of 23 patients with giant-cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was undertaken in order to assess the behaviour of the non-specific markers of the disease activity, the erythrocyte sedimentation rate (ESR) and other acute phase markers, particularly the C-reactive protein (CPR) and serum amyloid A apolipoprotein (apo SAA) levels during induction of disease remission by prednisone therapy, and possible further recurrence of GCA and/or PMR. The apo SAA measurement is more sensitive than the CRP measurement in determining disease activity (97% and 61%, respectively). The specificity of apo SAA is greater than ESR in the determination of inactive disease (86% and 77%, respectively). In some cases with clinically active disease the ESR and CRP were normal, whereas the apo SAA was always elevated. We conclude that the apo SAA measurement in combination with clinical data and other laboratory parameters may be useful in the management of GCA and/or PMR.