Slide Session :OS-NEP-05 ; Nephrology : Ormond`s Disease (Retroperitoneal Fibrosis) and Idiopathic Mesenteritis in Internal Medicine: Possible IgG4-Related Diseases?

( Marta Perez De Lis Novo ),( Roberto Perez Alvarez ),( Soledad Retamozo ),( Pilar Brito Zeron ),( Xavier Bosch ),( Antoni Siso Almirall ),( Jaume Villalta ),( Ricardo Alvarez Vijande ),( Alfonso Lope 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyse the possible existence of features associated with IgG4-related disease (IgG4-RD) in patients diagnosed with retroperitoneal fi brosis or mesenteritis. Methods: Study cohort including patients diagnosed with retroperitoneal fi brosis and/ or mesenteritis by imaging studies (CT) in a university hospital during the last 20 years. Results: A total of 22 patients diagnosed with retroperitoneal fi brosis (15 patients) or mesenteritis (7 patients) are described (6 women and 16 men, with a mean age at diagnosis of 64.1 years, range: 46-82. The main clinical manifestations present at diagnosis were abdominal/back pain (n=14), general malaise/fever (n=7) and the presence of edema/thrombosis (n = 6); in one patient, diagnosis was made incidentally by imaging techniques. CT showed infl ammatory masses affecting retroperitoneal (n=17), mesenteric (n=7) and vascular structures, including iliac arteries (n=3), aorta (n=2), renal arteries (n=2) and cava (n=2). In 7 (32%) patients, involvement of other organs suggestive of IgG4-RD (liver/bile tract in 2 cases, periaortitis in 2 cases, pleura, lymph nodes and skin in 1 each, respectively) was found. Diagnosis was confi rmed by biopsy in 8 patients (36%); in any patient, studies to rule out IgG4-RD were performed. The main treatments included corticosteroids (n=17), immunosuppressive agents (azathioprine in 5, methotrexate in 1 and mycophenolate in 1), surgery (n = 5) and the placement of urinary catheters (n = 4). After a mean follow-up of 73 months, 7 patients died (32%) patients (4 of them due to septic shock). Conclusions: Ormond`s disease is a rare clinical entity but associated with a signifi cant morbidity and mortality. His recent inclusion in the clinical spectrum of IgG4-RD diffi cult their retrospective diagnosis, although this study and others recently published suggest that about half of the cases could correspond to IgG4-RD.

Poster Session : PS 0388 ; Infectious Disease ; Infectious Spondylodiscitis: The Importance of Clinical Suspicion

( Marta Perez De Lis Novo ),( Alexandre Perez Gonzalez ),( Melania Estevez Gil ),( Emma Filgueira Davila ),( Julian Fernandez Martin ),( Roberto Perez Alvarez ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyse the epidemiological, clinical, diagnostic and therapeutic features related to the development of spondylodiscitis in a cohort of Spanish patients. Methods: A retrospective analysis of 75 cases of infectious spondylodiscitis diagnosed in university hospital between 2000 and 2013. Results: We studied 75 patients with a mean age of 63 + / - 20 years, of which 67% were male. Time average evolution of disease prior to consultation was 4.2 months. The main symptom was back pain or back pain (90%) The most frequent location was the lumbar spondylodiscitis (74%), 60% of patients had one or more associated diseases (Diabetes:20%; COPD: 18%; tumors: 17%). Furthermore, 50% of them suffered from heart disease, being the most frequently hypertensive. 23% of patients carried immunosuppressive therapy, mainly corticosteroids (90%). In 53 patients (70%) could be performed a certain diagnosis, with Staphylococcus aureus the most frequent (41%) followed by S. epidermidis (17%), and Streptococcus (15%). Blood cultures were positive in 60% of cases and surgical biopsy was performed in 37% of the patients. 8 cases had endocarditis criteria, 6 of which were fulfi lled by S. aureus. MRI was performed in 75% cases, being in all cases, pathological. The average length of treatment was 12 weeks, with the most commonly used antibiotics cloxacillin, vancomycin and ceftriaxone. 18% of patients underwent surgery, performed laminectomy and drainage of abscesses. During evolution 6 patients died. 10 patients (8%) had sequelae neurological. Conclusions: Spondylodiscitis is a rare disease in adults, but with high morbidity and mortality due to the diffi culty of diagnosis. Insidious development and the lack of specifi city of the symptoms it interferes with the diagnosis and treatment early, so a high index of suspicion is essential.

Poster Session:PS 0207 ; Family Medicine : The Cardiovascular Paradox of Sle in Family Medicine: A Case-Control Study of the Prevalence and Management of Cardiovascular Disease in Patients with Sle Followed in a Primary Care Center

( Marta Perez De Lis Novo ),( Roberto Perez Lvarez ),( Pilar Brito Zeron ),( Antoni Siso Almirall ),( Belchin Kostov ),( Mireia Marti Villalta ),( Albert Bove ),( Hoda Gheitasi ),( Soledad Retamozo ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyze the prevalence of SLE in the field of primary care and to evaluate the management of cardiovascular risk factors (CVRF) in comparison with a non-autoimmune control population. Methods: Analysis of the diagnostic accuracy of SLE by primary care physicians using medical record audit (EMR) in 3 health centers including a population of 44,184 inhabitants. The prevalence of CVRF and clinical cardiovascular disease (CVD) in the SLE population was evaluated and compared with a control population of patients without autoimmune disease matched for gender. Results: 145 patients were identifi ed as SLE. After a case-by-case audit, 112 (77%) patients were confirmed as having SLE, representing a prevalence of 0.25%: 92% were women, with a median follow-up of 11.3 years: death was recorded in 8.9%. The comparison of the main characteristics between SLE and the control group showed that SLE patients had a lower mean age (53.2 vs 60.5, p=0.001), a lower frequency of dyslipidemia (26% vs 47%, p=0.001), a lower mean total cholesterol (199.5 vs 211.3 mg/dL, p=0.023) and a lower mean systolic blood pressure (119 vs. 124.2 mmHg, p=0.043). In contrast, patients with SLE had a higher frequency of renal disease (32.1% vs 12.1, p<0.001), cerebrovascular disease (8.0% vs 1.6%, p=0.027) and non-fatal cardiovascular events (17.0% vs 4.8%, p=0.003). Conclusions: The level of diagnostic accuracy of SLE in our primary care area was high. We found a ‘cardiovascular paradox “: despite having a signifi cantly better degree of control of the main CVRF, and even being a younger population, a higher prevalence of CVD was observed in SLE patients, suggesting that this autoimmune disease is, per se, a cardiovascular risk factor.

Poster Session:PS 0206 ; Family Medicine : Comprehensive Initial Training for Medical Doctors Starting in 1980 in Musashino Red Cross Hospital

( Marta Perez De Lis Novo ),( Roberto Perez Lyarez ),( Pilar Brito Zeron ),( Antoni Siso Almirall ),( Belchin Kostov ),( Mireia Marti Villalta ),( Albert Bove ),( Hoda Gheitasi ),( Soledad Retamozo ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Medical education for medical school graduates in Japan greatly changed after World War II. From 1948, the General Headquarters (GHQ), the Supreme Commander for the Allied Powers imposed internship medical school graduates as early clinical training, internal medicine for 5 months, surgery for a month, obstetrics and gynecology for a month, public health for a month, for initial year. This system was unpaid before the nation examination, and abolished in 1968 by the campus dispute spread throughout Japan. Subsequently became mainstream medical center by the universities and colleges, but did not develop the training of general practitioners and family doctors in Japan because of aiming for the priority of specialization by university faculty of medicine. Musashino Red Cross Hospital (MRCH) started comprehensive initial training for medical doctors since 1980. One of the reason is that The Japan Red Cross Society as the most important philosophy advocates disaster medicine and its realization in general medical education is very important. Methods: MRCH employed the intern doctors by general invitation examination, and educated them for two years. In principle mandatory training period within 2 years in internal medicine, surgery, pediatrics, obstetrics and gynecology training, psychiatry, and regional medical training. Results: From 1980 to now MRCH did general medical education to more than 200 doctors. These doctors are working around the world. In Japan, from 2004 Initial general medical training was compulsory to all new medical doctors for two years. Conclusions: Comprehensive initial training for medical doctors is very important in general medicine for all the generations and the disaster medicine. In Japan from the year 2020 general medicine training under the new medical program scheduled.

Slide Session : OS-RHEU-07 ; Rheumatology : Predicting Death in Patients with Primary Sjogren Syndrome: Prognostic Factors and Standardized Mortality Ratio in Comparison to the General Population (RESSPGEAS- SEMI)

( Pilar BRITO ZERÓN ),( Marta PEREZ DE LIS NOVO ),( Belchin KOSTOV ),( Roser SOLANS ),( Guadalupe FRAILE ),( Carlos SUÁREZ CUERVO ),( Arnau CASANOVAS ),( Francisco Javier RASCÓN ),( Rami QANNETA ),( R 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyze prognostic factors and standardized mortality ratio (SMR) with respect to the general population in a cohort of Spanish patients with primary Sjogren`s syndrome (SS). Methods: In October 2013, the RESSP-GEAS-SEMI database included 1045 consecutive patients who met the 2002 SS-criteria. Hazard ratios (HR) and confi dence intervals (95% CI) obtained in the adjusted regression model were calculated. The SMR was estimated using the life tables of the general population of Spain in 2012. Results: The cohort included 982 (94%) women with a mean age at diagnosis of 54 years and a mean disease evolution of 118 months; 115 (11%) patients died due to systemic disease (n=18), infection (n=21), cardiovascular disease (n=35), hematologic malignancy (n=10) and other causes (n=31). The SMR for the total cohort of patients (adjusted for age and sex with the general Spanish population) was 4.66. Survival rates at 5, 10, 20 and 30 years were 96.0%, 90.5%, 80.9% and 60.4%, respectively. The Cox-regression analysis identifi ed the following baseline variables at diagnosis associated with death: male gender (HR 2.98, p<0.001), altered parotid scintigraphy (HR 2.81, p=0.043), lymphopenia (HR 1.63, p=0.034), anti-La antibodies (HR 1.51, p=0.034), low C3 (HR 1.93, p=0.034), low C4 (HR 2.06, p=0.016), monoclonal gammopathy (HR 1.81, p=0.047) and cryoglobulins (HR 2.58, p<0.001). The main baseline factors associated with mortality caused by systemic disease were systemic-activity at diagnosis, cytopenias, monoclonal gammopathy, cryoglobulins, and hypocomplementemia. Conclusions: Primary SS should not be considered a mild disease, since mortality is almost 5 times greater with respect to general population, with an overall survival at 20 years of 81%. Patients with a lower survival are those who present with active disease at diagnosis and associated immunological markers of B-cell hyperactivity.

Slide Session : OS-CAD-03 ; Cardiology : Spanish Registry of Autoimmune Congenital Heart Block in Babies of Mothers Carrying Anti-Ro/la Antibodies (Rebacc-Geas-Semi)

( Pilar Brito Zeron ),( Marta Perez De Lis Novo ),( Pilar Rosich ),( Carles Tolosa ),( Joaquim Oristrell ),( Luis Saez Comet ),( Mercedes Perez Conesa ),( Jose Antonio Vargas Hitos ),( Jose Mario Sabi 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyze the outcomes and therapeutic management of affected pregnancies with autoimmune congenital heart block (aCHB). Methods: Retrospective multicenter study in Internal Medicine Departments; inclusion criteria consisted of: aCHB of any type (I, II or III), fetal EFE and/or cardiomyopathy, cardiac block diagnosed in utero or in the first postpartum month, and mothers carrying anti-Ro52, Ro60 and/or La autoantibodies. Results: A total of 25 pregnancies with aCHB were retrospectively analyzed in 21 anti-Ro/La+ mothers. The mean maternal age at the time of pregnancy with aCHB was 33,25 years. Only 2 mothers received treatment prior to the first affected pregnancy (hydroxychloroquine and hydroxychloroquine+prednisone). Cardiac block consisted of type I (n=1), type II (n=6) and type III (n=18). At diagnosis of aCHB, 15/22 women were treated with dexamethasone (one of them, along with IVIG) and 2/22 with ritodrine. Preventive treatment with IVIG was administered in 2 pregnancies in which a recurrence was observed. Pregnancy was interrupted in 7/25 pregnancies at a mean week of 23.43 (18.2-37), while 18/25 of pregnancies gave a live birth baby with a mean age of 35.71 weeks of birth (30-40). 11 babies required pacemaker implantation, 9 immediately after birth and 2 in the neonatal period (1 at 5 years of age and another at 12). Of the 15 pregnancies with aCHB treated with dexamethasone, 12 achieved pregnancy to term (1 type II disappeared, with no changes in the remaining cases) and there were 3 fetal deaths despite treatment. Of the 7 pregnancies not treated with dexamethasone, 3 babies were born alive (no reversal of the blockade) and there were 4 fetal deaths. Conclusions: aCHB is a serious problem with a fetal mortality of 28% and a high requirement for neonatal pacemaker placement (61%).

Poster Session : PS 0640 ; Respiratory Medicine ; Infl uence of Epidemiological Profi le in the Clinical Expression of Sarcoidosis: Study of 160 Patients with Systemic Disease

( Pilar Brito Zeron ),( Marta Perez De Lis Novo ),( Roberto Perez Alvarez ),( Jacobo Sellares ),( Soledad Retamozo ),( Xavier Bosch ),( Fernanda Hernandez ),( Josep Manel Santos ),( Antoni Siso Almira 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyse the infi uence of the epidemiological profi le in the disease expression of a large series of patients with sarcoidosis. Methods: Study cohort including 160 patients diagnosed with sarcoidosis in the last 10 years. The diagnosis of sarcoidosis was based on clinical criteria and imaging studies, together with the histopathological demonstration of non-necrotizing granulomas, and excluding other granulomatous diseases, mainly infectious (tuberculosis). Results: There were 106 women and 54 men, with a mean age at diagnosis of 46.87 years. The main clinical manifestations present at diagnosis were respiratory symptoms (40%), followed by general symptoms (31%), skin lesions (29%) and the incidental fi nding of imaging fi ndings in asymptomatic patients (18%). 37% of patients had adisease onset <40 years. This early onset of disease was reported mainly in males (44% vs 28%, p=0.027) and was associated with a higher frequency of general symptoms (42% vs 25%, p=0.023), erythema nodosum (29% vs 16%, p=0.041), uveitis (14% vs. 5%, p=0.05) and joint involvement (17% vs 5%, p=0.014), but with a lower frequency of interstitial lung disease (25% vs 42%, p=0.028) and splenic involvement (0% vs 7%, p=0.037). With respect to the differential presentation of the disease according to gender, women diagnosed with sarcoidosis had a higher mean age at diagnosis (48.8 vs 42.8 years, p=0.017), a higher frequency of skin involvement (35% vs 13%, p=0.003) and a lower frequency of pulmonary (34% vs 52%, p=0.022), hepatosplenic (2% vs 9%, p=0.044) and nervous system (3% vs 13%, p=0.032) involvements in comparison with males. Conclusions: An early disease onset (<40 years) was mainly associated with general and cutaneous involvement, while sarcoidosis in men affects more frequently vital organs.

Slide Session : OS-HEM-03 ; Hematology : Hemophagocytic Syndrome in Internal Medicine: Iden-tification of Infectious Triggers, Therapeutic Manage-ment and Mortality in 88 Patients (REGHEM-GEAS-SEMI)

( Pilar BRITO ZERÓN ),( Marta PEREZ DE LIS NOVO ),( Roberto PÉREZ ALVAREZ ),( Pedro MORAL MORAL ),( Aleida MARTÍNEZ ZAPICO ),( Guadalupe FRAILE ),( Eva FONSECA ),( María VAQUERO HERRERO ),( Angela RUI 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyze the therapeutic management and the main epidemiological and clinical characteristics related to survival in a large series of patients with hemophagocytic syndrome (HS) diagnosed in Departments of Internal Medicine. Methods: In June 2013, the Study Group of Autoimmune Diseases (GEAS-SEMI) creates a national registry of patients with HS. Patients were diagnosed according to the fulfillment of the criteria of the Histiocytosis Society in 1991 and updated in 2004. Results: At June 15, 2014, the REGHEM registry included 88 patients with HS, 35 (40%) men and 55 (60%) women, with a mean age at diagnosis of 49.16 years (range 12- 84 years). During the admission that led to the diagnosis of SH, acute infections were identified in 50 (57%) patients, including viruses (n=20), bacteria (n=13), mycobacteria (n=8) and parasites/fungi (n=13). Patients were treated with corticosteroids (n=40), etoposide (n=12), cyclosporin A (n=12), methotrexate (n=4), tacrolimus (n=2) rituximab (n=3), intravenous immunoglobulins (n=2) and chemotherapy (n=5). A total of 44 (50%) patients died. The main factors associated with mortality were analytical parameters at diagnosis such as the presence of severe anemia (Hb <9 g/L, 89% vs 66%, p=0.01), platelet count <100,000/mm3 (96% vs 64%, p<0.001), neutropenia <1000/mm3 (59% vs 39%, p=0.044), and bacterial infections as precipitating agent (77% vs 45%, p=0.034); a clinical presentation including lymphadenopathy was associated with a lower mortality (59% vs 39%, p=0.044). Conclusions: Hemophagocytic syndrome is a severe multisystemic disease associated in nearly 50% of cases with an acute infection, and usually requires vital support in intensive care units. Despite this and the use of a complex therapeutic approach, half of the patients died. The main prognostic factor identified is the presence at diagnosis of severe cytopenias and the coexistence of bacterial infections.

Slide Session : OS-RHEU-08 ; Rheumatology : Minimally-Invasive Biopsy of Minor Salivary Glands in Internal Medicine: Searching for Systemic Infi ltrative Diseases

( Pilar Brito Zeron ),( Marta Perez De Lis Novo ),( Soledad Retamozo ),( Lluisa Alos ),( Albert Bove ),( Hoda Gheitasi ),( Belchin Kostov ),( Antoni Siso Almirall ),( Roberto Perez Alvarez ),( Manuel 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To analyze the safety and utility of minor lip biopsy by using the minimally invasive technique, performed in the Department of internal medicine, in patients presenting with immunonegative sicca syndrome. Methods: Prospective analysis of 122 patients (100 women, mean age 60 years) with sicca syndrome and negative anti-Ro/La antibodies in which minimally invasive biopsy of minor salivary glands was performed. Results: The most common histopathological feature consisted of lymphoplasmacytic infi ltration in 57 (47%) patients, followed by fi brosis in 46 (38%) and acinar atrophy in 32 (26%); the type of lymphoplasmacytic infi ltrate was detailed in 53 patients (21 lymphocytic, 20 plasmacytic, and 12 lymphoplasmacytic). According to the lymphocytic classifi cation of Chisholm and Mason, 53 (44%) were classifi ed as normal, 42 (35%) grade I, 11 (9%) grade II, 8 (7%) grade III and 7 (6 %) grade IV. Histopathologic diagnosis were: normal in 46 patients, non-specifi c sialadenitis in 42, primary Sjogren`s syndrome in 26 (15 as the fi nal diagnosis, 11 and probable), and other diagnoses in 6 (fat infi ltration in 5, systemic amyloidosis in 1); no cases of infi ltration by granulomas or IgG4+ were found. The presence of fi brosis was detected more frequently in women (43% vs 14%, p=0.014); the existence of fi brosis (67.70 vs 55.76 years) and acinar atrophy (69.50 vs 56.71 years) correlated with increasing age. No correlation between the degree of infi ltration and diagnostic or immunological features was found. Only 8% patients reported transient adverse events. Conclusions: In 21% of patients with an immunonegative sicca syndrome, a diagnosis of primary SS was confi rmed by minimally invasive biopsy, whereas 35% of patients disclosed a non-specifi c chronic sialadenitis, which could refl ect a “mild” SS that have no place in the current classifi cation criteria of this disease.

Slide Session : OS-RHEU-03 ; Rheumatology : Genetic Variability of The CD5 Lymphocytic Immunoreceptor and Clinical Expression of Systemic Autoimmune Diseases Related to B-Cell Hyperactivity

( Pilar Brito Zeron ),( Hoda Gheitasi ),( Marta Perez De Lis Novo ),( Noelia Armiger ),( Maria Jose Soto Cardenas ),( Myriam Gandia ),( Albert Bove ),( Xavier Bosch ),( Soledad Retamozo ),( Miriam Aka 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: To investigate the mechanisms involved in lymphocyte activation mediated by the CD5 immunoreceptor in patients with systemic autoimmune diseases related to B-cell hyperactivity. Methods: A total of 508 patients were analyzed (273 primary Sjogren syndrome patients, 135 SLE patients, 47 SS associated HCV patients and 53 controls). CD5 genotyping receptor was analyzed by PCR-SBT technique with the detection of the SNP7 (rs2241002) andSNP26 (rs2229177). The homozygous haplotype CC/CC was classifi ed as inductor of autoimmunity, whereas the heterozygous haplotype CC/TT was a protective factor. Results: The haplotype CC/CC was found in 7.5% of controls vs 19% of patients with primary SS fulfi lling the 2002 criteria (p=0.047), 12% of SS-1993 criteria (p=0.39), 18% of SLE (p=0.10) and 21% of SS-HCV patients (p=0.049); the protective haplotype CC/TT was observed in 28% of controls vs 19% of patients with primary SS-2002 criteria (p=0.15), 13% of SS-1993 criteria (p=0.01), 15% of SLE (p=0.04) and 15% of SS-HCV patients (p=0.10). A specifi c analysis was carried out in patients with primary SS-2002 criteria comparing the clinical and immunological features of patients carrying protective haplotypes (n=33) and those carrying inductor haplotypes (n=33). A higher frequency of anti-La/SS-B antibodies (67% vs 39%, p=0.048) and a trend for an increased frequency of extraglandular involvement (52% vs 36%), neutropenia (33% vs 18%), ANA (91% vs 82%), FR (53% vs 48%) and low levels of C3 (12% vs 3%) was found in carriers of inductor haplotypes with respect to those carrying protective haplotypes. Conclusions: We found a higher frequency of the CC/CC haplotype (associated with increased autoimmunity) of the gene that encodes the immunoreceptor lymphocytic CD5 in SS patients, that was related to an increased extraglandular systemic activity, especially a higher frequency of anti-La/SS-B antibodies.