M. Freire

Autoimmune Manifestations of Kikuchi Disease

OBJECTIVES Kikuchis disease (KD) has been associated with the presence of autoantibodies, systemic lupus erythematosus (SLE), and other autoimmune diseases. The aim of this study was to assess the frequency of autoimmune manifestations in a KD cohort with a long follow-up. METHODS Twenty patients with histologically confirmed KD since January 1990 until December 2010 were studied; 12 of them were periodically followed up as outpatients. Another 7 patients were contacted by telephone to offer them a specific consultation and a complete autoimmunity study. RESULTS Thirteen of 20 patients were women (65%) with a mean age of 29 years (range, 15-79). The age at diagnosis was higher in men (44 vs 27 years, P < 0.05). Lymphopenia was present in 75% of the patients (15/20) and was the more frequent hematological abnormality. The mean follow-up of the 17 patients included in the autoimmunity study was 119 months (range, 15-252). Autoimmune diseases were detected in 9 women (53%): SLE was diagnosed in 4 patients (2 SLE before, 1 simultaneous, and 1 after KD), 2 patients developed primary Sjögrens syndrome after KD, 1 thyroiditis before KD, 1 SLE-like, and 1 antiphospholipid antibodies after KD. Leukocytoclastic vasculitis was found in 2 patients; 1 of them eventually developed SLE. Female sex, painful adenopathies, and cytopenias were significantly associated with autoimmune diseases. CONCLUSIONS Among patients with KD, only women developed autoimmune manifestations. Therefore, long-term follow-up and active surveillance of autoimmune diseases in patients with KD, especially women, are recommended.

High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

OBJECTIVE Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder causing mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is considered an uncommon complication of HHT whose impact on the survival of these patients is currently unknown. METHODS From January 1995 to December 2008, 29 hospitalized patients with definite HHT were included and followed until January 2011. Data on demographics, clinical symptoms and survival were recorded. PH was classified according to echocardiographic probability. RESULTS A CT angiogram was performed in 24 of the 29 patients with HHT and AVMs were detected in 16 of them (67%): hepatic in 58%, pulmonary in 33% and spinal in 3%; 37% had both pulmonary and hepatic AVMs. Transthoracic Doppler echocardiography (TTE) was performed in 21 patients. PH was considered possible in 4 (14%) and probable in 9 (31%). The mean age at diagnosis was lower in patients with PH than in patients without PH (54±16.5 years vs 73±8.8 years, p=0.002). PH was more prevalent in patients with AVMs (56 vs. 23%, p=0.036). The mean follow-up of the entire cohort was 6±4.4 years (range: 2 months-17 years), during this time 18 patients died (62%; mean age 73±8.1 years). Patients with PH died at a younger age (68±8.4 vs. 79±2.7 years, p=0.015) than those without PH. CONCLUSIONS PH is a severe condition that significantly reduces survival on HHT patients. PH should be suspected in all HHT patients with dyspnea and hepatic AVMs.

SAT0329 Scleroderma in Men in Northwestern Spain: Differentiating Clinical Features

Background 85-90% of patients with systemic sclerosis (SSc) are women, so there are few series that have evaluated distinguishing clinical features in men (1). Objectives To describe clinical features of the male subgroup of a cohort of patients diagnosed with scleroderma in our hospital and evaluate the differences within the female subgroup. Methods Encoded patients with diagnosis of SSc in our hospital from 1985 until December 2013 were collected. They were classified into four groups using a modification of LeRoy and Medsger proposed criteria (2): diffuse systemic sclerosis (dcSSc), limited systemic sclerosis (lcSSc), systemic sclerosis sine scleroderma (ssSSc) and pre-scleroderma (pre-SSc). Medical records were reviewed, recording clinico-epidemiological data and results of immunological tests. Results Of the 114 patients diagnosed with SSc in this period, 17 (15%) were male, the group described below: 10 (59%) were classified as dcSSc and 7 (41%) as lcSSc. Mean age at diagnosis was 49 years. 9 (53%) had a history of exposure to SSc related toxic - 8 silica, 1 vinyl chloride-. All patients had positive ANA, 3 ACA, 8 Scl70, 3 dsDNA, 2 antiRo, 1 antiLa, 1 antiRNP and 1 antiSm. Capillaroscopy was performed in 3 patients (18%), finding a scleroderma pattern throughout, with a presence in all three of giant capillaries and capillary loss and ramified capillaries in two. Along the follow-up (mean 11 years), 15 patients (88%) had Raynauds phenomenon, 10 (59%), dyspnea, 9 (53%) ulcers, 7 (41%) telangiectasia, and 4 (23%) digestive disorders. Interstitial lung disease was documented in 10 patients (55%) and PAH in 3 (16%). 12 patients (71%) died during the monitoring, an average of 10 years after initial diagnosis. The cause of death was: respiratory failure in 4 (33%), heart failure in 2 (17%), carcinoma in 3 (25%), cirrhosis in 1 (8%) and unknown in 2 (17%). Multivariate analysis comparing men with women subgroup, showed in male less age at diagnosis (p 0.017) and death (p 0.001), a predominance therein of exposure to toxic (p 0.05), dcSSc (p 0.003), Scl70 positivity (p 0.004), interstitial lung disease (p 0.002), and presence of giant capillaries (p 0.05), capillary loss (p 0.02) and ramified capillaries (p 0.003) in nailfold capillaroscopy. No statistically significant difference was found in mortality or survival time from diagnosis. Conclusions 1. In more than half of our male patients with SSc, a related toxic was found, mainly silica. 2. Our male subgroup was differentiated clinically in an younger occurrence of the disease, a predominance of dcSSc, positivity for Scl70, presence of interstitial lung disease, and advanced endothelial damage capillaroscopic patterns. References J.-B. Gaultier et al. Systemic sclerosis in men. La Revue de médecine interne 2008: 181–186. LeRoy EC, Medsger TA, Jr. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28(7):1573-6. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2014

Synovial fluid eosinophilia: a case series with a long follow-up and literature review

OBJECTIVES To establish the frequency and describe the characteristics of a cohort of patients with SF eosinophilia (SFE) and a long clinical follow-up. A systematic review of the literature on this topic was performed. METHODS From November 2005 to May 2010, 982 consecutive arthrocentesis procedures performed at a tertiary care hospital were reviewed. Clinical and analytical data of patients with SFE at the time of diagnosis and during follow-up until 31 January 2012, were recorded. According to the percentage of eosinophils in SF, SFE was classified as minor (<10%) or major (>10%). Also, a literature search of all publications on eosinophilic synovitis found in MEDLINE, EMBASE and Web of Science without publication date restrictions was performed. RESULTS Eosinophils in SF were found in 10 of 982 (1.02%) patients: minor SFE was recorded in three patients, all of them with haemorrhagic fluid and without peripheral eosinophilia. Major SFE was found in seven patients, and only two of them had peripheral eosinophilia. In six patients, an underlying cause of the arthritis was found. Only one patient was classified as having idiopathic SFE. Most SFE promptly resolved with NSAIDs without relapses or new deformities. The literature search identified 56 patients with SFE; 49 of them (88%) had major SFE and 7 (12%) had minor SFE. CONCLUSIONS Eosinophils are infrequently found in SF, and in most cases peripheral eosinophilia was not detected. Most patients with SFE had a benign course with prompt resolution and few relapses.

FRI0289 Cerebrovascular disease in the antiphospholipid syndrome

Background Antiphospholipid syndrome (APS) is a thrombophilic disorder characterized by recurrent arterial and venous thrombosis, and also pregnancy losses associated to antiphospholipid antibodies (APA). Cerebrovascular disease (CVD) is the most common and severe arterial thrombotic manifestation in patients with APS. Objectives 1.To determine the prevalence and the type of CVD in patients with APS. 2.To compare the recurrent strokes, affected brain areas, hospitalization, treatment and mortality between patients with CVD, with and without APS. Methods Retrospective and, descriptive study of patients with APS (Sidney criteria) and CVD followed for a long period of time in a specific Systemic Autoimmune Diseases and Thrombosis Unit. Subsequently, retrospective case-control study was performed. Case definition: patients with CVD attributable to APS. Control definition: patients with CVD without APS. The controls were matched with cases by sex and age (within the same decade). Chi-square and t-student were used, using the statistical package SPSS22.0. Results 25 patients (25/88 28,4%) had CVD, 19 (76%) of primary APS and 6 (21%) of secondary APS. 17 patients (71,6%) were female. The mean age was 57,48±21,52 [range 13–89], with a mean follow-up of 8,64±6,72 years. 24% of patients had atrial fibrillation, 80% had one cardiovascular risk factor and 48% had two or more factors (hypertension 68%, hypercholesterolemia 36%, diabetes 20%, tabaquism 4%). Echocardiographic study was performed in 72% of patients with APS. Mitral valve was mainly involved. Most CVD were ischemic events (92%). The brain areas most involved were the basal ganglia (36%), together with the parietal and temporal lobe (16% respectively). 40% had two or more affected regions. 44% of the patients had two or more episodes of stroke. Lupus anticoagulant was positive in 40%, anticardiolipin antibodies in 76% and anti-β2 glycoproteinI antibodies in 20%.No differences were found with isotypes of APA and recurrent thrombosis or mortality. The treatment applied was oral anticoagulants (OAC) (48%), antiplatelet therapy (APT) (20%) and low molecular weight heparin (20%). In 10 patients (40%) CVD was diagnosed before APS (mean 8.64±6.7 years). The mortality was 44% and 40% of the patients were hospitalized more than once. When we compared the groups: treatment, performed echocardiogram, valvular disease, affected brain areas, recurrent strokes and follow-up time, revealed significant differences (see table 1).OAC were more used in the patients with APS and APT was the most common in control group. Valvular disease was more frequent in case group. The brainstem and the frontal lobe were the areas more affected in patients without APS.The number of strokes was higher in APS group. The patients with CVD and APS had a long-term follow-up. Tabe 1 Age OAC APT Vascular risk factors Valvular disease Brain stem Frontal lobe Strokes (≥2) Mortality Follow-up CVD with APS 57,48±21,52 48% 20% 80% 20% 0% 12% 44% 40% 8,64±6,72 CVD without APS 61,16±20,6 0% 72% 68% 0% 20% 36% 16% 44% 2,04±2,99 p 0,76 p<001 p<001 p 0,33 p 0,02 p0,02 p 0,04 p 0,03 p 0,77 p<001 Conclusions The prevalence of CVD in our series of APS was 28.4% and most often were ischemic events. Most of the patients were women with high recurrent strokes and mortality. No differences were found with isotypes of APA and recurrent thrombosis or prognosis. CVD with APS patients had more recurrent strokes and longer follow-up. Disclosure of Interest None declared

AB0501 Sjögren Syndrome, Cancer Incidence and Mortality in Vigo Area

Background Sjögrens syndrome (SS) is a systemic autoinflammatory disease with a well known epidemiological and laboratory characteristics. Its main symptoms are derived from exocrine glands affectation. Like other inflammatory diseases presents an increased incidence of malignancies. The diagnosis of this entity and subsequent identification of factors associated with the occurrence of tumors is important for early detection and management Objectives To analyze the epidemiological, clinical and laboratory characteristics and the occurrence of lymphoma and mortality in a cohort of patients in a tertiary hospital diagnosed with SS Methods Descriptive analysis of data collected retrospectively of patients with SS (criteria American-European 2002) between November 1989 and November 2012 the Hospital of Vigo Results We describe 58 patients with SS of which 86% were women with a mean age of 53±15 years.Mean follow-up time was 69 months (range5–343). Mean age at diagnosis was 50 years (range 26–87 years).Only 6 (10%) had a secondary SS associated with Lupus Erythematosus Systemic, Rheumatoid Arthritis, Scleroderma, Mixed Connective Tissue Disease and Sarcoidosis. We do not find any autoimmune disease associated with organ-specific.The 84.5% and 93% had ocular and oral symptoms respectively.The parotid scintigraphy was performed in 25 (43%), which was pathological in 37 (68%).Salivary gland biopsy was performed in 30 (52%), 28 were diagnostic (93%).The most common extraglandular involvement was the joint (50%),followed the skin and lymph nodes (both 12%).24% have Raynauds phenomenon with capilaroscopia nonspecific. Others, were central and peripheral nervous system (8.6% each one), respiratory (7%) and kidney (3%). None had muscle involvement. Anti-Ro was positive in 83% (59% also had anti-La) and anti-La was positive in only 48%.Antinuclear antibodies and rheumatoid factor were positive in 95% and 67% respectively. 22 (38%) had low C4 and 10 (17%) had low C3. Cryoglobulins were positive in 2 (3%). Only two patients have anti-Ro and anti-La negatives (they had xerostomia and xerophthalmia, parotid scan and biopsy compatible with the diagnosis). The cancer incidence was 10%, 2 were solid tumors (one pancreatic adenocarcinoma and another invasive ductal breast cancer) and 4 were hematologic (diffuse B lymphoma, angioimmunoblastic T lymphoma, Hodgkins lymphoma and nodal MALT). All those who developed lymphoma they had previous lymphadenopathy. The mortality rate was 12%: 4 neoplasia (2 lymphomas, 1 pancreas and 1 breast), 2 infections, 1 cerebral hemorrhage. Conclusions The 89.6% of our series had a primary SS with the same collected clinical and serological features literature. The development of a neoplasm was the leading cause of death (57.1%). In our cohort over half the patients who had lymphadenopathy developed a hematologic malignancy. SS patients have a higher risk for hematologic malignancy, so based on our data, the occurrence of lymphadenopathy it is a warning sign which requires us to actively seek a lymphoproliferative process References Ramon-Casals et al. Guias de práctica clínica de la Sociedad Española de Medicina Interna. Diagnόstico Sjögren, 2009. Ramos-Casals M. et al. Prymary Syndrome Sjögren. BMJ, 2012 Turesson C et al. Malignancy as a Comorbidity in rheumatic diseases. Rheumatology, 2013 Disclosure of Interest None declared

AB0527 Comparison of Two Initial Prednisone Dose Regimens in Giant Cell Arteritis

Background Giant cell arteritis (GCA) is a vasculitis affecting large vessels and it is the most frequent type in patients over 50 years old. Although glucocorticoids (GC) still remain the mainstay of treatment in all these cases there is no yet clear evidence about optimal initial dose, regimen and relapses predictors and treatment [1, 2]. Objectives To assess the characteristics of treatment, relapse and outcomes of a biopsy-proven GCA patients and to compare these items between groups based on initial oral prednisone dose. Methods We performed a retrospective review of all patients diagnosed of biopsy-proven GCA in our institution (Complejo Hospitalario Universitario de Vigo) between 1 January 2000 and 31 December 2014. Additionally, they fullfilled at least 2 of other 4 1990 ACR classification criteria. Epidemiological, clinical and laboratory data, treatment and outcome of all these patients at diagnosis and during follow-up were analysed. We also compared groups by initial oral prednisone dose (≤40mg/day vs >40mg/day) using Cox models. Results During study period 70 patients were identified and analysed. Mean age at diagnosis was 77±7 years old and fifty-one (73%) were female. Charlson index was ≤1 in 83% of cases. Most frequent presenting symptoms were headache (87%), polymyalgia rheumatica (57%) and jaw claudication (48.6%). Ischaemic manifestations at diagnosis were seen in ten patients (14.3%). Median ESR and CRP was 88±26mm/h [31–140] and 92±88mg/dL [4–326] respectively. Median delay time from first symptom until diagnosis was 2 months [0–72]. We also analysed patients divided in two groups based on initial oral predisone dose (≤40mg/day [17 patients] vs >40mg/day [53 patients]). No differences was seen in sex, age, comorbidities (including cardiovascular risk factors), antiagregants/ immunosupressive therapy use or laboratory markers. Nevertheless prednisone dose at first month (30.2mg/day vs 48.6mg/day; p=0.001), time to reach ≤5mg/day of prednisone (11.8 vs 16 months; p=0.045) and total prednisone dose (7.2 vs 11.5 grams; p=0.001) were significantly higher in >40mg/day group although we did not see more GC-related adverse effects in this group (p=0.38). During follow-up period (median 29 months [3–140]) 18 patients had at least one relapse, however we did not observe statiscal differences between both groups (18% in ≤40mg/day vs 28.8% in >40mg/day; p=0.35). Time to first relapse (12±11.3 months in ≤40 vs 16±12.9 months in >40; p=0.67) and total treatment time (28±23.5 in ≤40 vs 35±25.1 months in >40) were similar in boths groups. We could not identified any factor that was related to relapses in our multivariate analysis. Twenty-two patients died during follow-up period but none were related with GCA. Conclusions High-dose prednisone was the most frequent initial treatment of GCA patients. Lower doses regimen could be as safe and effective as the high-dose regimen. Relapses were seen in ¼ of patients but we could not identified any factor associated with them. References Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. Lancet 2008; 372: 234–45. Les I, Pijoan JI, Rodríguez-Άlvarez R et al. Effectiveness and safety of medium-dose prednisone in giant-cell arteritis: a retrospective cohort study of 103 patients. Clin Exp Rheumatol 2015; 33 (Suppl 89): S90–97. Disclosure of Interest None declared

THU0068 Clinical Risk Factors Associated with the Development of Systemic Disease in Patients with Isolated HLA-B27 Uveitis

Background HLA-B27 uveitis has been defined as a unilateral acute syndrome without associated systemic disease [1]. However, in some patients the ocular disease precedes the occurrence of systemic diseases as ankylosing spondylitis (AS), reactive arthritis (ReA), spondyloarthritis (SpA), undifferentiated spondyloarthritis (UspA), SpA associated with psoriasis and SpA associated with inflammatory bowel disease (SpA-IBD) Objectives To determine how many patients with isolated HLA-B27 uveitis will develop systemic disease and to identify the clinical risk factors associated with their occurrence Methods Patients with HLA-B27 and at least 1 episode of uveitis diagnosed by an ophthalmologist were identified among all adult patients (>14 years) consecutively typed for HLA-B27 in our hospital from January 1, 2006 to December 31, 2011. These patients were seen in our Unit to perform a complete rheumatologic examination to look for prior or concurrent systemic disease associated with HLA-B27. Also, a comprehensive clinical, radiological and analytical evaluation to exclude autoimmune and infectious diseases that may cause uveitis was carried out. Follow-up was defined as the period of time from the first episode of uveitis confirmed by an ophthalmologist to the latest medical evaluation. Values are shown as average and standard deviation (SD) and percentage for quantitative and qualitative variables respectively. The T test and chi squared are used for comparisons Results During the 6 years of study period 1803 patients were typed for HLA-B27, of which 293 tested positive (16%). Of these patients, 42 (14%) had at least 1 episode of uveitis. 14 of these patients (33%) were excluded from the study because prior or concurrent systemic disease related with HLA-B27 positivity (8 AS, 4 UspA, 1 ReA, 1 SpA-IBD). So, a cohort of 28 patients with isolated HLA-B27 uveitis, 15 males (54%), 36.9years ± 14.19 (15-60), was follow-up during a mean of 7.7 years ±5.89 (1-20). 9 patients (33%) developed systemic disease: 5 AS, 3 UspA and 1 SpA-IBD. The diagnosis of the systemic disease was made 3.7 years ±4 (0.5-12) after the onset of uveitis. Bilateral uveitis (including alternating uveitis) was identified as the only significant risk factor for the development of systemic disease, OR 8.3 (95% confidence interval 1.25-55.35, p=0.03), so a multivariate analysis was not performed.The risk for systemic disease was 1.8 times greater for patients with bilateral HLA-B27 uveitis than for patients with unilateral involvement. Significant differences with age, gender, location of the uveitis, chronicity, response to treatment and ophthalmic complications were not found between patients with isolated uveitis and those who developed systemic diseases Conclusions A third of patients who present with isolated HLA-B27 uveitis will develop associated systemic disease. Bilateral ocular involvement was identified as the only significant risk factor for the occurrence of systemic disease in the present cohort References Jakob E, Reuland MS, Mackensen F, Harsch N, Fleckenstein M, Lorenz HM, et al. Uveitis Subtypes in a German Interdisciplinary Uveitis Center- Analysis of 1916 Patients. J Rheumatol 2009; 36:127-36 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5872

Autoimmune hepatitis and hepatic arteritis

Autoimmune hepatitis and hepatic arteritis SIR, The presence of hepatic arteritis is a common finding in the hepatic biopsies of patients with PAN. Nevertheless, its impact on other collagen-vascular diseases (CVDs) is much lower. In an extensive pathological series of 120 autopsies and 40 hepatic in vivo biopsies taken from patients with a history of CVD, Matsumoto found signs of liver arteritis in 100% of patients with PAN, but in only 18% of patients with SLE, the last all belonging to autopsy samples [1]. So far the association between hepatic arteritis and autoimmune hepatitis (AIH) has not been published. We report a patient with a diagnosis of AIH and a simultaneous histological finding of hepatic vasculitis. The patient was a 62-year-old woman with a medical history of a mild self-limiting neutropoenia episode during the post-operative period after a hysterectomy due to myomas 10 years earlier. The patient was admitted to our hospital due to a 1 week clinical picture of intense asthaenia, jaundice and coluria. She was not taking medicines or herbal products, and was not suffering from dry eye syndrome, photosensitivity, oral aphthae, alopecia or Raynauds disease. Physical examination highlighted cutaneous-mucous jaundice and a 3-cm painful hepatomegaly. The analysis revealed thrombopoenia (platelet count of 44 000/ml). The PT and activated partial thromboplastin time were 18 and 21.6 s, respectively. Complement component 4 was decreased (3.6 mg/dl). Bilirubin was 14.8 mg/dl, aspartate aminotransferase was 1272 IU/l, alanine aminotransferase was 1120 IU/l, ALP was 711 IU/l and g-glutamyl transpeptidase was 123 IU/l. The g-globulin levels were elevated with IgG 2790 mg/dl. Antibody studies were positive for ANA (1/320, nucleolar pattern), anti-dsDNA (1/320) and anti-Ro/SSA, and negative for RF, ANCA, AMA, ASMA, lupus-like circulating anti-coagulant, antibodies to liver kidney microsome, anti-cardiolipin, b 2-glycoprotein I, soluble liver antigen and CCP. Cryoglobulins were negative. Serologies for hepatotropic virus were negative and ceruloplasmin and a-1 anti-trypsin levels were normal. Quantification of proteins in urine was 0.24 g/24 h. Abdominal US showed a normal-sized liver. We did a transjugular biopsy of the liver, and the histopathological study showed the FIG. 1 AIH with arteritis. (a) Interface hepatitis with erosive hepatocellular necrosis. Numerous plasma cells (arrows), a common finding in AIH, are seen in the infiltrate. (b) An arteriole with a focus of necrotizing vasculitis, which is characterized by fibrinoid necrosis of its wall accompanied by a neutrophilic infiltrate with nuclear dust.