L. Saez

Early- versus Late-Onset Systemic Sclerosis: Differences in Clinical Presentation and Outcome in 1037 Patients

AbstractPeak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ⩽30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.

Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity

Abstract The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome. A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ± 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear–nose–throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ± 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.

THU0226 Clinical features and mortality causes in a large cohort of spanish patients with anca associated vasculitides

Background Antineutrophil cytoplasmic autoantibody (ANCA) associated vasculitides (AAV) are uncommon chronic and relapsing diseases characterized by inflammatory cell infiltration and necrosis of blood vessel walls. They often have overlapping clinical and pathological manifestations that make difficult to reach a precise diagnosis. AAV are still related to a high mortality and morbidity in spite of current therapies. Objectives To describe the clinical features present at diagnosis and to investigate the causes of mortality in a large cohort of patients with AAV from Spain. Methods We analyzed the demographic, clinical and laboratory features of all patients diagnosed with AAV in 13 different Hospitals from Spain, between January 1995 and December 2010. The statistical analysis was performed using the SPSS v15.0. Results Two hundred and forty-six patients were included: 109 WG, 97 MPA and 40 CSS. ANCA were positive in 87% of cases: 35.4% C-ANCA and 51.6% P-ANCA. The mean age at diagnosis was 55.3±17.4 years. The mean time to diagnosis was 2±13.7 months. The most frequent symptoms at diagnosis were fever (50.4%), constitutional symptoms (49%), arthralgia (55%), hypertension (30%), hemoptisis (21.5%) and purpura (21%). Renal failure was present in 48.8% of patients, pulmonary involvement in 45.5%, pulmonary-renal syndrome in 11%, and cardiac involvement in 9%. Sensory peripheral neuropathy was detected in 26% of cases and cerebrovascular accidents (CVA) in 4.5%. Ear, nose and throat (ENT) was observed in 35% of cases and eye involvement in 15%. Renal involvement was significantly higher in patients with P-ANCA and ENT involvement in patients with C-ANCA. Necrotizing glomerulonephritis on biopsy was evidenced in 30% of cases. All patients received oral glucocorticoid treatment. Cyclophosphamide was given to 209 patients (39% intravenous and 46% oral). Dialysis was required in 18% of cases and plasma exchange in 6.5%. During the follow-up 34.6% of patients suffered bacterial infections, 12% sepsis, 14% opportunistic infections, and 4.9% developed neoplasm. Opportunistic infections were most frequent in patients with severe renal failure (p=0.018), and severe leukopenia (p<0.000). Fifty-one (20.7%) patients died: 33 with MPA, 15 with WG, and 3 with CSS. Mortality was significantly related to severe renal failure (p<0.000), nephrotic syndrome (p=0.001), hemoptisis (p=0.044), cardiac involvement (p=0.003), CVA (p=0,042), sepsis (p=0.038) opportunistic infections (p=0.007), and neoplasm (p=0.023). Conclusions The clinical characteristics seen here are similar to those in previous series. The presence of severe renal, pulmonary or cardiac involvement was significantly associated with a poor clinical outcome. MPA had a poorer prognosis that WG or CSS. References Lane SE, Watts RA, Shepstone L, et al. Primary systemic vasculitis: clinical features and mortality. Q J Med 2005; 98:97-111 Disclosure of Interest None Declared

THU0300 Central nervous system involvement in granulomatosis with polyangiitis (WEGENER) in a large series of patients with anca-associated vasculitides (AAV).revas STUDY-GEAS-SEMI

Background GPA is a necrotizing systemic vasculitis that usually involves ENT, lung and kidneys. Neurological manifestations appear in 25–50% of patients, usually involving peripheral nervous system. CNS involvement, has been reported in only 7–11% of cases Objectives to describe the clinical features and outcome of patients with GPA and CNS involvement in a large series of patients with AAV Methods multicenter retrospective-longitudinal study that encompassed patients diagnosed with AAV between Jan 1995 and Nov 2014 in 21 Centres from Spain (REVAS Study). Statistical anlysis was performed using SSPS vs20 package Results 455 patients (188 GPA, 167 MPA and 100 EGPA) were included. Mean age at diagnosis was 55.7±17.2y. ANCA were positive in 86.8% of cases (35.8% C-ANCA, 51% P-ANCA). Median time to diagnosis was 4 weeks (IQR 10). Median follow-up time was 80 months (IQR 105). Neurological involvement was documented in 156 (34.5%) patients, but only 33 (7.3%) presented CNS involvement at disease onset. From those patients, 20 (60.6%) had GPA. Mean age at diagnosis of patients with GPA and CNS involvement was 51.1±16.7y. ANCA were positive in all cases (15 C-ANCA-PR3, 5 P-ANCA-MPO). Headache was the main neurological symptom (60%) followed by sensory (45%) and motor impairment (35%). MRI and/or angio-CT scan were performed in all cases. Cerebral ischaemic lesions were observed in 10 patients, and granulomatous lesions in 9, including pachymeningitis (n=6), spinal cord pachymeningitis (n=2) and isolated granulomatous lesions (n=1). Lumbar puncture was performed in 8 (40%) patients and revealed CSF abnormalities in 70. Diagnosis was confirmed by meningeal biopsy (n=2), ENT biopsies (n=5) and renal biopsy (n=2) in patients with CNS granulomatous lesions, and by renal, pulmonary or peripheral nerve biopsy in patients with CNS ischemic lesions. Headache was predominant in patients with granulomatous lesions, while sensory and motor impairment were predominant in patients with ischemic lesions. Mean BVAS at disease onset was 29.2±9.7, significantly higher than in GPA total cohort (18.2±9.2). Renal involvement was more common in patients with ischaemic lesions than in those with granulomatous (80% vs. 40%, p<0.001), and ENT involvement in patients with granulomatous forms (70% vs. 50%, p<0.005). Most patients (70%) received oral CF for induction therapy. Two patients received rituximab. For maintenance therapy, 25% of patients received AZA, 20% MMF and the remaining CF. 70% of patients received TM-SX. During follow-up, 58.8% and 40% of patients developed bacterial and opportunistic infections, respectively. Infections were related to oral CF therapy (p=0.029). Long-term neurological sequelae were noted in patients with ischaemic lesions (40%) and spinal cord pachymeningitis (100%) Conclusions Patients with GPA and CNS involvement have more severe disease at presentation and more treatment-related side effects than patients without CNS involvement. Long-term neurological sequelae are more frequent in patients with ischaemic lesions and spinal cord pachymeningitis Disclosure of Interest None declared

FRI0388 Ussefulnes of Bvas and Ffs at Diagnosis To Predict Survival in Anca Associated Vasculitis (AAV)

Background The Birmingham Vasculitis Activity Score (BVAS), and the Five Factor Score (FFS) at the time of diagnosis have been shown useful to asses prognosis in AAV (1,2), but few studies have been done comparing these tools to predict survival Objectives To compare the usefulness of BVAS vs 3, 1996 FFS and 2009 FFS at the time of diagnosis, to predict survival in a large cohort of patients with AAV from Spain Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan1995 and Nov13 in 20 Hospitals from Spain (REVAS Study). Patient survival was assessed by life-table analysis using the Kaplan-Meier method. Statistical analysis was done using SPSS vs21 Results 455 patients were included: 188 (41.3%) GPA, 167 (36.7%) MPA and 100 (22%) EGPA; 50.8% were men. Mean age at diagnosis was 55.7±17.2 y. ANCA were positive in 86.8% of cases: 35.8% C-ANCA and 51% P-ANCA. Median time to diagnosis was 4 weeks (IQR 10). Median follow-up time was 80 months (IQR 105) for global population. Renal involvement was present in 61.5% of cases, lung involvement in 54.7%, pulmonary-renal syndrome in 16.9%, neurological involvement in 34.5%, and cardiac involvement in 12.7%. ENT was observed in 44.8% of cases and eye involvement in 18.9%. Mean BVAS at diagnosis was 17.7±7.7; 1996FFS was ≤1 in 390 (85.8%) patients, and 2009FFS was ≤2 in 361 (79.4%). All patients received oral corticoids, 342 (75.1%) cyclophosphamide (49.7% IV and 50.3% oral), and 6.6% biological therapy. Dialysis was required in 16.4% of cases. During the follow-up, 39.1% of patients suffered bacterial infections, 9.2% sepsis,12.7% opportunistic infections and 5.3% neoplasms. One hundred thirty (28.6%) died:74 (44.3%) with PAM, 42 (22.3%) with GPA and 14 (14%) with EGPA (p<0.001). Univariate analysis showed that BVAS, 1996FFS and 2009FFS at diagnosis were significantly related to death (p<0.001). A multifactorial Cox regression analysis including the three activity scores confirmed that all of them were statistically related to survival rate but the stronger predictor of poor prognosis was the 2009FFS with a HR 2.7. This result was confirmed by curve ROC: 2009FFS showed the greater area under the curve (75%), in front of 1996FFS (66%) and BVAS (62%) Conclusions BVAS and FFS at diagnosis are signifivantly related to survival in AAV, but the stronger predictor of survival is the 2009 FFS. References Merkel P, Cuthbertson D, et al. Comparison of disease activity measures for ANCA-associated vasculitis. ARD 2009;68:103–6 Guillevin L, Seror R, et al. The Five-Factor Score Revisited Assessment of Prognoses of Systemic Necrotizing Vasculitides. Medicine 2011;90:19–27 Disclosure of Interest None declared

SAT0288 Eosinophilic Granulomatosis with Poliangeitis (EGPA): Clinical Features and Outcome in A Large Serie of Spanish Patients

Objectives To analyze the demographic, clinical, laboratory features and outcome of patients with EGPA in a large cohort of Spanish patients with AAV Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between January 1995 and December 2012 in 19 Hospitals from Spain (REVAS Study). Statistical analysis was performed using the SPSS vs17. Results 87 patients with EGPA (mean age 52.5±16.1 yr) from 405 with AAV were analyzed. Asthma was present in all cases and preceded EGPA by 6 months to 29 yr (mean 81.6 mo) except in 6 cases in which began simultaneously. A history of allergic rhinitis was noted in 42.5% cases with nasal polyposis in 23% and recurrent sinusitis in 49.4%. ANCA were positive in 66% cases (91% MPO ANCA). Mean follow-up was 82.5±75.3 months. The most frequent clinical manifestations at diagnosis were fever (44%), arthralgia (47%), constitutional symptoms (41%), neurological symptoms (54%), and purpura (35%). Renal failure was present in 14% cases, reno-pulmonary sd. in 4.6% and cardiac involvement in 27.6%. Renal and neurological involvement were more frequent in positive ANCA patients (p=0.005) and cardiac involvement in ANCA negative (p=0.001). Chest-x-ray showed lung infiltrates (56.3%) and nodules (16%). Eosinophilia was present in all cases. Serum IgE levels were raised in 73.3% of tested patients. A total of 101 biopsies were done (25 nerve,15 lung,6 renal,7 nasal,38 skin,4 bowel,2 pericardial,2 liver,2 pleural) and showed eosinophil infiltrates in 52 cases and necrotizing vasculitis in 47. Oral prednisone (1mg/kg) was given to all patients, iv metilprednisolone to 45%, iv cyclo-phosphamide (CF) to 41.4%, oral CF to 24.1%, azathioprine to 21.8%, and mycophenolate to 5.7%. Rituximab was successfully administered in 2 cases with refractory disease. Leukopenia was more frequent in patients treated with oral CF (p<0.000). During the follow-up, 27.6% patients developed bacterial infections, 11.5% opportunistic infections and 9 (10.3%) died. Dead was mainly related to infections (p=0.011) and refractory disease. EGPA patients had less renal involvement (p=0.005) and more cardiac involvement (p=0.002) than those with GPA and MPA and a lower mortality (p=0.001) Conclusions patients with EGPA have less severe clinical manifestations than those with GPA and MPA and a lower mortality. Renal involvement is rare and cardiac involvement frequent, as previously described. Most patients with FFS>1 improve with corticosteroids and CF. RTX may be useful in patients with refractory disease. The overall EGPA survival rate is good and dead is mainly related to infections and refractory disease Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4714

SAT0173 Alveolar Haemorrhage in Anca-Associated Vasculitides: Cliical Features and Prognosis

Background Alveolar haemorrhage (AH) can be a mild or life-threatening manifestation of ANCA-associated vasculitides (AAV), but its prognostic impact and specific characteristics remain unclear. Objectives To determine the clinical features related to AH and the prognostic value of this manifestation in patients with AAV. Methods We analyzed the demographic, clinical and laboratory features of AH in a large series of patients with AAV from 18 different Hospitals of Spain, entered in the Spanish Registry of Systemic Vasculitides (REVAS) between January 1995 and June 2012. Statistical analysis was performed using the SPSS vs. 17. Results There were 343 patients with AAV (144 GPA, 131 MPA and 68 EGPA), with a mean age of 55.1 ± 17.8 yr (range: 17-91) at AAV diagnosis. ANCA were positive in 86.69% of cases (PR3-ANCA in 35.6% and MPO-ANCA in 51.3%). Mean follow-up was 78.6 ± 71.3 months. AH was present as an initial manifestation in 54 (15.7%) patients, 55.5% males and 44.5% females, mean age 57.4 ± 16.1 yr (range 21-84). Fifty-nine percent of patients had positive MPO-ANCA and 38.5% positive PR3-ANCA. Haemoptysis was present in 41 (77.8%) patients. The most frequent concomitant symptoms were fever (57.7%), constitutional symptoms (53.8%) and arthralgias (61%). Simultaneous renal failure (pulmo-renal syndrome) was present in 75% of patients and respiratory failure in 50%. Mechanical ventilation was required in 19.2% cases. Renal biopsy showed rapid crescentic glomerulonephritis in 52% patients. Lung biopsies found active vasculitis in 10 patients. Anemia was present in 96.2% of cases and severe renal failure (creatinine > 5.6 mg/dl) in 25%. Intravenous (iv) metilprednisolone was given to 80.8% of patients, iv cyclophosphamide (CF) to 61.5%, oral CF to 44.2%, azathioprine to 28.8%, methotrexate to 3.8%, mycophenolate to 9.6% and iv immunoglobulin to 7.7%. Plasma exchange was needed in 28.8%, and dialysis in 42.3%. During the follow-up, 48.1% of patients developed bacterial infections (42.3% pneumonia), 26.9% opportunistic infections, and 5.8% neoplasm. Five (9.3%) patients underwent kidney transplantation, and 14 (25.9%) died. AH was significantly related to the presence of haemoptysis (p< 0.000), severe renal failure (creatinine> 5.6 mg/dl, p<0.000), anaemia (p < 0.000), MPO-ANCA (p=0.033), rapid crescentic glomerulonephritis (p=0.004), dialysis p < 0.000, and pneumonia development (p=0.008). AH was not related to dead (p= 0.156). Conclusions In our series AH was clearly related to MPA and positive MPO-ANCA, in contrast to other reported series (1). Minor or major haemoptysis was the principal event leading to AH diagnosis. AH alone was not predictive of a poor prognosis, although it was associated with high morbidity (mechanical ventilation, pneumonia). Concomitant AH and acute glomerulonephritis (pulmo-renal syndrome) was one of the most severe manifestations of AAV. References Kostianovsky A et al. Alveolar haemorrhage in ANCA-associated vasculitides: 80 patients’ features and prognostic factorsClin Exp Rheum 2012. Lee RW. Pulmonary renal vasculitis syndromes. Autoimmun Rev 2010; 9 :657-60. Disclosure of Interest None Declared