Roser Solans-Laqué

Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Objectives To validate the two recently developed disease activity indexes for assessment of primary Sjögrens syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). Methods A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjögrens Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. Results Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.

IgG4-Related Disease: Results From a Multicenter Spanish Registry.

AbstractIgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.

Age-related survival and clinical features in systemic sclerosis patients older or younger than 65 at diagnosis

OBJECTIVEnTo analyse the differences in SSc clinical features and survival in patients aged > or = 65 years compared with young SSc patients.nnnMETHODSnOf a total of 319 SSc patients, we identified 67 (21%) patients aged >65 years. Demographical data such as SSc subsets, the cutaneous complaint, internal organ involvement and the causes of morbidity and mortality were collected. Results of the elderly and young patients were compared.nnnRESULTSnThere were 61 (91%) women and 6 (9%) men aged > or = 65 years. The limited SSc (lSSc) subset was more prevalent in elderly than in young patients (74.6 vs 54%, P = 0.002). Pulmonary disease (86.6% in elderly vs 73.8% in young patients, P = 0.034) and cardiac involvement (70.1% in elderly vs 49.6% in young patients, P = 0.004) were significantly more prevalent in elderly patients. In contrast, signs of oesophageal involvement (43.3% in elderly vs 57.5% in young patients, P = 0.040) were less frequent in aged patients. In addition, pulmonary and heart disease appeared significantly earlier after the diagnosis in patients aged > or = 65 years. Mortality was significantly higher in elderly than in young patients (35.8 vs 19%, P = 0.005), but when standardized mortality ratios (SMRs) were analysed, there was no significant mortality increase in the elderly.nnnCONCLUSIONnIn elderly patients, the lSSc subset is more prevalent than the diffuse. Pulmonary and cardiac involvement are more prevalent in aged patients and appears sooner after the disease diagnosis. SSc is clearly related to increased mortality, although it is not significant in the elderly group.

Churg–Strauss Syndrome: An evolving paradigm

The Churg-Strauss Syndrome is an ANCA-associated vasculitis, an inflammatory multisystem disease with preference to the respiratory tract. Peripheral and tissue eosinophilia are the pathological hallmarks of this condition. The etiopathogenesis is unknown but some cytokines appear to play a central role and could be targets for new therapies.

Sequence analysis of TMEM173 exon 5 in patients with systemic autoimmune diseases

Abstract Background: Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in the TMEM173 gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs. Methods: We aimed at detecting the reported three mutations of transmembrane protein 173 (TMEM173) exon 5 in 100 patients suffering from: systemic lupus erythematosus (SLE) (nu2009=u200922), primary antiphospholipid syndrome (PAPS) (nu2009=u200920), systemic sclerosis (SSc) (nu2009=u200920), dermatomyositis (DM) (nu2009=u200920), and vasculitis (nu2009=u200918). Samples from 19 healthy controls were also included. Sequence analyses were performed from the derived TMEM173 exon 5 PCR fragment amplified from DNA obtained from whole blood. Results: Neither mutations nor single nucleotide polymorphisms (SNPs) in the exon 5 of the TMEM173 gene were detected. Just the rs7380272 SNP, located in the intronic region upstream exon 5, was detected in some patients and controls. The allele frequency of this SNP, though, was not statistically different between the patients groups and the control group. Conclusions: Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of the TMEM173 gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, as TMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway.

AB0449 Isolated aortitis as an atypical presentation of giant cell arteritis

Background The most common causes of aortitis are the large-vessel vasculitis, although it also is associated with several other rheumatologic diseases. Giant cell arteritis (GCA) is the most common form of large vessel vasculitis (1). Because aortic inflammation has no symptoms until complications arise, aorta has been believed to be uncommon target of the disease. However, aortic involvement has been estimated to occur in up to 18% with GCA, but some studies marks than in early histological proven GCA any degree of thickening of the abdominal aorta may be found in up to 27% of patients (2). Objectives To describe the presence of isolated aortitis as a presentation of GCA without typical clinical symptoms. Methods We included all the patients diagnosed of CGA in our hospital from 1991 to 2011, according to the American College of Rheumatology (ACR) classification criteria. Statistical analysis was performed using the SSPS vs. 15.0. Results Among the 174 patients with GCA, 124 were women (70.9%) and 50 men (29.1%). Mean age at diagnosis was 76 years (51-92). Typical symptoms at presentation were headache in 150 (86.2%), intermittent claudication of the muscles of mastication in 93 patients (53.4%), constitutional syndrome in 84 (48.3%), polymyalgia rheumatic syndrome in 74 (42.5%), fever in 38 (21.8%), permanent visual loss in 51 (29.3%), and amaurosis fugax in 25 (14.4%). Temporal artery biopsy was performed in 162 patients (93%), with intimal hyperplasia in 94 (54%), inflammatory infiltrate in 91 (52.3%), presence of giant cells in 80 (46%), and internal elastic lamina disruption in 62 (35.6%). Artery biopsy was normal in 9 patients (5.2%). Most frequently, the combination of typical clinical symptoms in the setting of an aged patient triggered the suspicion of GCA. However, in three patients the only clinical manifestations were weight loss and asthenia. In this clinical setting a thoracic-abdominal scan was performed with the suspicion of disseminated neoplasm and a diagnosis of isolated aortitis was made. One of the patients had floating thrombi attached to the wall of the aorta, probably secondary to aortitis. In front of the presence of an elevated acute reactants and an aortitis, a temporal artery biopsy was carried out, demonstrating the presence of a GCA. In this subset of patients, mean age was 74.3 years old (70-77), and raised erythrocyte sedimentation rate (mean 97) and anemia (mean 83 gr/l) was present in the three. Good evolution of the aortitis was seen in the three patients. Conclusions Aortic involvement in the acute phase of GCA is probably also more frequent than estimated because it is symptomatic in only a minority of patients. The presence of isolated aortitis should rule out a diagnosis of GCA, even though the absence of typical symptoms. References Martínez-Valle F, Solans-Laqué R., Bosch-Gil J, Vilardell-Tarrés M. Aortic involvement in giant cell arteritis. Autoimm Rev 2010 May;9(7):521-4. Agard C., Barrier J, Dupas B, Ponge T, Mahr A, et al. Aortic involvement in recent-onset giant cell (temporal) arteritis: a case-control prospective study using helical aortic computed tomodensitometric scan. Arthritis and Rheum 2008. 59(5): 670-6. Disclosure of Interest None Declared

AB0049 Eotaxin is overexpressed in churg-strauss syndrome compared to allergic asthma

Background Historically, allergic asthma has been considered the background of the development of Churg-Strauss Syndrome (CSS)1,2. Recently, a retrospective study comparing CSS and allergic asthma proved that respiratory atopy or allergy, at least to known and currently tested allergens, are present in approximately only the 30% of CSS patients, compared to near the 60% in patients with allergic asthma3. In the last years, a new family of chemokines, named eotaxins, have increasingly been proved to be a powerful chemotactic agent for eosinophils, inducing the activation and the migration of eosinophil to the inflammation site4. Indeed, an increase in eotaxin levels (though locally or in peripheral blood) has been proved in several eosinophil-mediated diseases (including allergy and CSS)5. Objectives The aim of our study is to focus in the differences and similarities at the immunologic response level between CSS and allergic asthma. In this first part of a wider work, we studied the levels of eotaxin in peripheral blood samples from patients with CSS and allergic asthma. Methods We collected peripheral blood samples from patients with CSS in clinical remission and from a cohort of patients with allergic asthma most of whom presented signs and symptoms of mild to moderate disease activity. We determined the concentration of eotaxin using a cytometric bead array (CBA) assay from BD™ using a monoclonal antibody against human CC chemokine eotaxin. Results We compared eotaxin levels from 19 patients with CSS in clinical remission with a cohort of 9 patients with allergic asthma. Results were as follows: Conclusions Indeed, eotaxin play an important role in both diseases. Nonetheless, in CSS reaches higher levels, probably translating a prominent polarization of the T cell response towards a Th2 profile. Notably, despite lacking clinical evidence of CSS activity, eotaxin levels remain elevated, highlighting the presence of a treatment resistant immunological activity. References Solans R, Bosch JA, Perez-Bocanegra C, Selva A, Huguet P, Alijotas J, et al. Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients. Rheumatology (Oxford) 2001;40(7):763-71 Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999;78(1):26-37 Bottero P, Bonini M, Vecchio F, Grittini A, Patruno GM, Colombo B, et al. The common allergens in the Churg-Strauss syndrome. Allergy 2007;62(11):1288-94 Conroy DM, Williams TJ. Eotaxin and the attraction of eosinophils to the asthmatic lung. Respir Res 2001;2(3):150-6 Polzer K, Karonitsch T, Neumann T, Eger G, Haberler C, Soleiman A, et al. Eotaxin-3 is involved in Churg-Strauss syndrome--a serum marker closely correlating with disease activity. Rheumatology (Oxford) 2008;47(6):804-8 Disclosure of Interest None Declared

Takayasu's arteritis relapse

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 18 mars 2017

Alteration of IgG4 levels in cerebrospinal fluid in IgG4-related disease

Dear Editor, Immunoglobulin G4-related disease (IgG4-RD) is an uncommon condition characterized by fibrosis and IgG4 lymphoplasmacytic infiltrates in diverse organs of unknown aetiology. Ig4-related pachymeningitis has been rarely described, but it can account for up to one-third of idiopathic hypertrophic pachymeningitis. Dural biopsy is the gold standard for the final diagnosis. Pathological diagnostic criteria have been proposed by Lu et al. Della Torre et al. are the only group who have studied the usefulness of cerebrospinal fluid (CSF) IgG4 determination as a diagnostic tool for central nervous system (CNS) IgG4-RD.

AB0548 Interstitial Lung Disease (ILD) in Primary SjÖGren Syndrome: Clinical, Immunological and Radiological Features and Outcome

Background Interstitial lung disease has been described in patients with pSS but there are limited data on its prognosis on the basis of clinical, immunological and radiologic findings, and pathologic diagnosis Objectives To analyze the clinical, immunological, radiological features, and the outcome of patients with pSS and interstitial lung disease Methods All patients diagnosed at our Department as having pSS according to the European-American Consensus criteria (EACC) between January 1992 and January 2013, and followed-up prospectively, were included. Chest-x-ray, high resolution CT (HRCT) scans, complete pulmonary function tests (PFT) with TLCO were performed in all cases. Histological study was done if possible Results 244 patients (233 women, 11men, mean age at pSS diagnosis 55.6 years ±14.5 - range 17 to 86 years-) were included. Thirty-two (12.7%) patients developed ILD. The mean age at ILD diagnosis was 61.8 yr (range 33 to 87 yr). No patient was smoker. The most frequent initial symptoms were cough and dyspnoea. Raynaud phenomenon was reported by 50% of patients and fatigue by 65.6%. Arthritis was present in 65.9% of cases, bronchiectasis in 40.6%, liver involvement in 28.1%, peripheral neuropathy in 18.8%, and interstitial nephropathy in 15.6%. The interval between pSS diagnosis and ILD development was 6.9 years (in 9 patients ILD was diagnosed before pSS diagnosis). All patients showed positive AAN, 90.6% polyclonal hypergamma-globulinemia, 72% RF, 37.5% anaemia, 12.5% leukopenia (<4000), 15.6% lymphopenia (<1000), 9.4% low C3 levels and 15.6% low C4 levels. Antisintetase antibodies were tested in all but 7 cases and only 2 patients showed PL12 antibodies positivity and 1 PmScl-75. On chest-x-ray all patients showed bilateral consolidation, reticulonodular infiltrates, or multiple cysts. The most frequent HRCT patterns were NSIP (n=16), UIP (n=11), LIP n=(2) and OP (n=1). ILD was related to the presence of anti-Ro/SSA antibodies (p=0.006), anti-La/SSB antibodies (p=0.018), RF (p=0.012), AMA (p=0.003), hypergamma-globulinemia (p<0.000) and low levels of complement fraction C4 (p=0.048). ILD was most frequent in patients with Raynauds phenomenon (p<0.000), arthritis (p=0.002), polyneuropathy (p=0.006), liver involvement (p=0.002), and kidney involvement (p=0.034). Twenty-seven (84%) patients received oral prednisone (1 mg/kg/day), 16 (50%), immunosuppressant drugs (7 AZA, 3 CF, 2 MTX, 3 MMF, 1 FK-506) and 2 Rituximab. One patient required lung transplantation. Fourteen (43.8%), patients died. Dead was directly due to lung infections and respiratory failure in 9 cases. The interval between ILD diagnosis and death was 8.6 years Conclusions In our series ILD development was more frequent in patients with Raynauds phenomenon, arthritis, liver disease and interstitial nephropathy. The presence of anti-Ro/SSA and anti-La/SSB, RF, hypergammaglobulinemia and hypocomplementemia was also related to ILD development. NSIP was the commonest radiologic pattern as seen in patients with systemic sclerosis and polymyositis/dermatomyositis. ILD was clearly related with a poor prognosis Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3353