Search

Introduction Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment. Methods We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not. Results Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [−0.1 (−4.8, 4.69), P = 0.988] or in SRC [0.7 (−2.2, 3.7), P = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s.d.) 7.6 (5.8) years vs 2.9 (5.3); P = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P Conclusion There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC.

Sarcoidosis is a systemic granulomatous disease with a highly variable clinical impact. Accurate prognostic evaluation is fundamental to establish the best therapeutic approach. Multiorgan disease and especially the involvement of vital organs, such as the heart, are associated with worse outcomes and often require more aggressive therapy. Here, we describe the case of a young adult with sarcoidosis with lymph node, pulmonary, hepatosplenic, and cardiac involvement. This clinical scenario emphasizes the importance of a thorough prognostic assessment and highlights some of the main unmet clinical needs for the risk stratification and management of these patients.

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15 years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points > 65 years-old), male gender (+1 point), lcSSc subset (−1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart (+1 point) and renal involvement (+2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p = .189), intermediate risk (26.5% vs. 25.5%, p = .911) and high risk (47.8% vs. 59%, p = .316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p = .530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.

To analyze whether immune-mediated diseases (IMDs) occurs in sarcoidosis more commonly than expected in the general population, and how concomitant IMDs influence the clinical presentation of the disease.We searched for coexisting IMDs in patients included in the SARCOGEAS-cohort, a multicenter nationwide database of consecutive patients diagnosed according to the ATS/ESC/WASOG criteria. Comparisons were made considering the presence or absence of IMD clustering, and odds ratios (OR) and their 95% confidence intervals (CI) were calculated as the ratio of observed cases of every IMD in the sarcoidosis cohort to the observed cases in the general population.Among 1737 patients with sarcoidosis, 283 (16%) patients presented at least one associated IMD. These patients were more commonly female (OR: 1.98, 95% CI: 1.49-2.62) and were diagnosed with sarcoidosis at an older age (49.6 vs. 47.5years, P0.05). The frequency of IMDs in patients with sarcoidosis was nearly 2-fold higher than the frequency observed in the general population (OR: 1.64, 95% CI: 1.44-1.86). Significant associations were identified in 17 individual IMDs. In comparison with the general population, the IMDs with the strongest strength of association with sarcoidosis (OR5) were common variable immunodeficiency (CVID) (OR: 431.8), familial Mediterranean fever (OR 33.9), primary biliary cholangitis (OR: 16.57), haemolytic anemia (OR: 12.17), autoimmune hepatitis (OR: 9.01), antiphospholipid syndrome (OR: 8.70), immune thrombocytopenia (OR: 8.43), Sjögren syndrome (OR: 6.98), systemic sclerosis (OR: 5.71), ankylosing spondylitis (OR: 5.49), IgA deficiency (OR: 5.07) and psoriatic arthritis (OR: 5.06). Sex-adjusted ORs were considerably higher than crude ORs for eosinophilic digestive disease in women, and for immune thrombocytopenia, systemic sclerosis and autoimmune hepatitis in men.We found coexisting IMDs in 1 out of 6 patients with sarcoidosis. The strongest associations were found for immunodeficiencies and some systemic, rheumatic, hepatic and hematological autoimmune diseases.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Objective To analyze the differences in characteristics and prognosis between alcoholic and nonalcoholic patients with Wernicke encephalopathy (WE). Patients and Methods A retrospective observational cohort of 468 patients diagnosed with WE with at least 2 Caine criteria was selected from all patients discharged with a diagnosis of WE from 21 medical centers in Spain from January 1, 2000, through December 31, 2012. Demographic, clinical, and outcome variables were described. Results Among the 468 patients, the most common risk factor was alcoholism (n=434 [92.7%]). More than one-third of patients (n=181 [38.7%]) had the classic WE triad of symptoms (ocular signs, cerebellar dysfunction, and confusion). Among 252 patients for whom magnetic resonance imaging data were available, 135 (53.6%) had WE-related lesions and 42 (16.7%) had cerebellar lesions. Of the 468 patients, 25 (5.3%) died during hospitalization. Alcoholic patients presented more frequently than nonalcoholic patients with cerebellar signs ( P =.01) but less frequently with ocular signs ( P =.02). Alcoholic patients had a significantly higher frequency of hyponatremia ( P =.04) and decreased platelet count ( P =.005) compared with nonalcoholics. Alcoholic patients were diagnosed earlier than nonalcoholics (median time to diagnosis, 1 vs 4 days; P =.001) and had shorter hospitalizations (13 vs 23 days; P =.002). Conclusion Compared with nonalcoholic patients, alcoholic patients with WE are more likely to present with cerebellar signs and less likely to have ocular signs. Diagnosis may be delayed in nonalcoholic patients. Mortality in the present series was lower than described previously.

Background Systemic sclerosis (SSc) is a systemic autoimmune disease with extremely heterogeneous clinical features and unknown etiology, although numerous studies suggest a relationship with environmental and occupational factors. So far there is little information on whether toxic substances can play a relevant role in its phenotypic expression (1). Objectives To analyze in a cohort of patients with SSc the proportion of patients exposed to toxic and their correlation with epidemiologic, clinical and serological data. Methods A survey was conducted aimed at the knowledge of the working life of patients from six centers belonging to the Spanish Scleroderma Registry (RESCLE), categorizing them in six groups: no potential exposure to toxic substances, potential exposure to silica, to hydrocarbons, to organic solvents, to mixed toxics (silica and/or hydrocarbons and/or organic solvents) and to another toxics. In all patients 87 epidemiological, clinical and analytical variables included in the registry were analyzed, carrying out a comparative study between groups. Results 225 SSc patients were selected. Of these, 81 patients (36%) had worked in professions with potential risk of toxic exposure, 64 women out of the 227 included (28%) and 17 men out of the 28 included (60%). The toxic agent most frequently involved was silica in 29 patients (35.8%), followed by hydrocarbons in 21 (25.9%), mixture of toxic substances in 21 other patients (25.9%), organic solvents in 4 patients (4.9%) and other toxic in 6 cases (7.4%). Toxic exposure was associated with a lower risk of being female (OR 0.15, p Conclusion In our cohort of 225 patients with SSc, 60% of male patients and 28% of women worked in a profession with a potential risk of toxic exposure. In this preliminary study, important differences were observed in the probability of a different phenotypic expression of the SSc according to the history of occupational exposure to toxins. Studies with a larger number of patients are needed to establish these associations in a solid way. References [1] Marie I, et al. Environmental risk factors of systemic sclerosis. Semin Immunopathol. 2015Sep;37(5):463-73. Disclosure of Interests None declared

© 2019 Usategui-Martín et al., [Purpose]: Several researchers have suggested that the rs243865 (16q13-q21) polymorphism in the promoter region of the metalloproteinase-2 (MMP-2) gene could be associated with an increased risk of developing age-related macular degeneration (AMD). However, previous results remain inconclusive. To clarify this controversy, we conducted a meta-analysis of the relationship between rs243865 of MMP-2 and AMD. [Methods]: We included 6 independent case-control studies involving 1,682 AMD patients and 2,295 healthy subjects. The association between the rs243865 polymorphism and AMD was examined by the overall odds ratio (OR) with a 95% confidence interval (CI). We used a recessive genetic model analysis, sensitivity analysis, and assessment of bias in our meta-analysis. [Results]: Our results showed that there was no significant association between the variant T allele (p-value = 0.10, OR [95%CI] = 0.95 [0.82–1.10]) or the CT+TT genotype (p-value = 0.16, OR [95%CI] = 0.92 [0.76–1.12]) of rs243865 MMP-2 polymorphism and the presence of AMD. [Conclusions]: The rs243865 MMP-2 polymorphism was not associated with an increased risk of developing AMD. The MMP-2 (-1306 C>T) promoter variant is unlikely to have a major role in AMD risk susceptibility., This work was supported in part by a grant from the Consejería de Educación, Junta de Castilla y León, Fondos FEDER (VA077P17) (JCP) and from Gerencia Regional de Salud de Castilla y León (INT/M/06/18) (AJC).

To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe.The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement.The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

Objectives To characterize the risk of solid and hematological cancer in a large, well-characterized cohort of patients with primary Sjogren syndrome (SjS). Methods The GEAS-SS multicenter registry is a network of Spanish reference centers with specific clinical experience in the management of SjS patients. By January 2016, we had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. Multivariate Cox proportional-hazards regression analysis allowed adjustment for age at diagnosis, gender and the statistically-significant baseline variables associated with cancer in the univariate analysis. The sex- and age-specific incidence rates (SIR) of cancer were estimated from 2012 Spanish mortality data modeling, using a set of age-, sex- and site-specific incidence:mortality ratios. Results After a mean follow-up of 91 months (9922.3 person-years), 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (34% of cancers, including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia (HR 1.06, p Conclusions One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with an enhanced risk of development of some types of non-hematological cancers (thyroid, oral cavity and stomach). Disclosure of Interest None declared

Objetive To assess the prevalence and causes of hepatobiliary involvement (HBI) in systemic sclerosis (SSc), to investigate the clinical characteristics and prognosis of SSc patients with HBI (SSc-HBI) and without HBI (SSc-non HBI), and to compare both groups according to the cutaneous SSc subsets. Methods 1572 SSc patients were collected in the RESCLE registry up to January 2015, and all hepatobiliary disturbances were recorded. We investigated the HBI related characteristics and survival from the entire SSc cohort and according to the following cutaneous subsets: diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc). Results Out of 1572, 118 (7.5%) patients had HBI. Primary biliary cholangitis (PBC) was largely the main cause (n = 67, 4.3%), followed by autoimmune hepatitis (n = 19, 1.2%), and anti-mitochondrial negative PBC (n = 6, 0.4%). Other causes of HBI were: secondary liver diseases (n = 11, 0.7%), SSc-related HBI (n = 7, 0.4%), nodular regenerative hyperplasia (n = 3, 0.2%), liver cirrhosis (n = 3, 0.2%), and HBI of unknown origin (n = 2, 0.1%). In multivariate analysis, HBI was independently associated to lesser risk of dcSSc (5.1% vs. 24.4%), and higher frequency of calcinosis (26% vs. 18%), left ventricular diastolic dysfunction (46% vs. 27%), sicca syndrome (51% vs. 29%), and anti-centromere antibodies (ACA, 73% vs. 44%). According to the cutaneous subsets, HBI was associated: (1) in lcSSc, to longer time from SSc onset to diagnosis (10.8±12.5 vs. 7.2±9.3 years), sicca syndrome (54% vs. 33%), and ACA (80% vs. 56%); (2) in ssSSc, to sicca syndrome (44% vs. 19%), and (3) in dcSSc, no associations were found. HBI was the cause of death in 2.3% patients but the cumulative survival according to the presence or absence of HBI showed no differences. Conclusions HBI prevalence in SSc is 7.5% and dcSSc is the least involved subset. PBC is the main cause of HBI. Patients with SSc-HBI exhibited specific clinical and immunologic profile. Survival is similar for SSc patients with HBI.

Aims To characterize a series of contemporary patients with alcohol-related Wernicke's encephalopathy (WE) or Korsakoff's syndrome (KS) and to update the current prognosis of disease. Methods Retrospective and prospective study of patients diagnosed with an alcohol-related WE or KS between 2002 and 2011 in a tertiary hospital. Socio-demographic, alcohol use characteristics, signs and symptoms, co-morbidity and blood parameters were obtained at admission. Patients were followed up until 2013 and causes of death were ascertained through the review of charts. Results Sixty-one patients were included (51 with WE and 10 with KS). Among patients with WE, 78% were men and age at diagnosis was 57 years (interquartile range (IQR): 49–66). Twenty-three percent fulfilled the classic WE triad. Regarding Caine's criteria for WE, 70.6% presented with at least two out of four signs or symptoms. Median follow-up of patients with WE syndrome was 5.3 years (IQR: 2.6–8.8), the cumulated mortality was 45% and death rate of 7.4 × 100 person-years (95% confidence interval (CI): 4.8–10.9). Overall, 50% of patients would be expected to die within 8 years of WE episode and main causes of death included serious bacterial infections (44.5%) and cancer (33.3%). Conclusions Survival of patients with an alcohol-related Wernicke–Korsakoff syndrome is poor; pursuing treatment of alcohol use disorder and early diagnosis of thiamine deficiency is a priority for improving clinical outcomes.

Aliment Pharmacol Ther 2011; 34: 1159–1172 Summary Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione-S-transferases (GST) have been associated with ALD vulnerability with controversial results. Aim To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta-analysis. Methods We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta-analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed. Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta-analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR = 1.43; 95% CI: 1.14, 1.78; P = 0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR = 2.04; 95% CI: 1.09, 3.80; P = 0.03). Conclusions Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione-S-transferase as a potential therapeutic target in alcoholic liver disease is reinforced.

A 67-year old male was brought to the hospital by his family because he had been suffering from somnolence, bradypsychia and gait disturbance for one week. He lived alone, reported an ethanol intake higher than 100-120 g/day. His diet was limited in quality and amount. The physical examination showed stigmata of chronic liver disease. The neurological exam revealed right-side cerebellar tremor, bilateral dysmetria and gait ataxia as well as hyporeflexia in the lower limbs. He was diagnosed of Wernicke encephalopathy. How should this patient be evaluated and treated?

Resumen Introduccion La identificacion de un paciente alcoholico plantea frecuentemente dificultades al ocultarse el consumo del toxico. Poder etiquetar como alcoholico a un enfermo con patologia aguda permite delimitar de forma mas precisa el diagnostico diferencial del sindrome que presenta. Objetivo Analizar el alcoholismo desde la perspectiva de la medicina interna, mediante la exposicion de un caso clinico discutido. Material y metodos Se presenta un paciente varon alcoholico cronico que acude al hospital por fiebre y dolor abdominal. Se expone el diagnostico diferencial de los diferentes problemas medicos que presenta, con referencias fisiopatologicas y se razona el procedimiento diagnostico y terapeutico. Conclusiones Se resalta la necesidad de identificar al paciente alcoholico y valorar e integrar en conjunto todos los problemas medicos que presenta.

Objective To perform a systematic review to analyze the association between occupational exposure to wood dust and cancer. Methods A systematic literature search of entries made in the MEDLINE-PubMed database between 1957 and 2013 was conducted to identify studies that had assessed the relationship between occupational exposure to wood dust and different types of cancer. A meta-analysis of selected case-control and cohort studies was subsequently performed. Results A total of 114 studies were identified and 70 were selected for review. Of these, 42 studies focused on the relationship between wood dust and nasal cancer (n = 22), lung cancer (n = 11), and other types of cancer (n = 9). Low-to-moderate quality evidence that wood dust acts as a carcinogen was obtained, and a stronger association between wood dust and nasal adenocarcinoma was observed. A lesser association between wood dust exposure and lung cancer was also observed. Several studies suggested that there is a relationship between wood dust and the onset of other cancers, although there was no evidence to establish an association. A meta-analysis that included four case-controls studies showed that workers exposed to wood dust exhibited higher rates of nasal adenocarcinoma than other workers (odds ratio = 10.28; 95% confidence interval: 5.92 and 17.85; P

Presented here is the first report of clinical reactivation of hepatitis B virus (HBV) in an HIV-infected patient who previously had anti-HBc as the only serological marker of past infection (anti-HBc alone). Reactivation occurred after lamivudine was removed from the patient's antiretroviral treatment regimen due to lack of virological response. HIV-infected patients frequently present anti-HBc alone, and in some cases this serological profile is associated with occult HBV infection. The current case demonstrates the importance of ruling out the possibility of occult infection in this patient group.

Wernicke encephalopathy is caused by thiamine deficiency in the central nervous system, and is defined by the triad of confusional symptoms, ocular alterations and ataxia. Some other factors may also predispose alcoholic patients to this deficiency. We report two patients with hyperglicaemia and ketoacidosis due to diabetes mellitus decompensation and chronic alcoholism who developed Wernicke encephalopathy before their hospital admission. The outcome was successful after intravenous thiamine administration and insulinotherapy. The presence of Wernicke encephalopathy in alcoholics with diabetic ketoacidosis, suggests that metabolic decompensation is essential in the onset of the disease.

Background HScore is a numeric scoring system recently proposed by Fardet et al in 2014, designed to estimate the risk of having hemophagocytic syndrome (HS) in adults. Objectives The objective of this study is to analyze the potential use of the HScore as a prognostic factor in a large cohort of Spanish patients with adult HS. Methods In June 2013, the Study Group of Autoimmune Diseases (GEAS-SEMI) created the National Registry of Adult Patients with HS. Patients were diagnosed according to the fulfillment of the Histiocytosis Society criteria proposed in 1991 and updated in 2004. The HScore includes 9 clinical, laboratory and histopathological criteria, and the score may range from 0 to a maximum of 337 points. Results By January 2015, the REGHEM registry included 111 adult patients with HS, 65 (59%) men and 46 (41%) women, with a mean age at diagnosis of 49.16 years (range 12-85 years); nineteen patients (17%) were not born in Spain (58% from Latin America, 21% from Africa and 16% from Asia). Tissular hemophagocytosis was confirmed in 97/107 (87%) cases. The main underlying diseases diagnosed before HS were autoimmune/rheumatological diseases in 36 (33%) patients, chronic infections in 24 (22%) and neoplasia in 25 (23%) patients. The great majority of patients required ICU admission and death occurred in 59 (53%). The HScore was retrospectively calculated in 61 patients in whom all the criteria required could be applied: the mean HScore was 230,03 (range, 58-306). No significant differences for the mean HScore were found with respect to gender, age at diagnosis, underlying diseases, or severe internal organ involvement (pulmonary, renal or central nervous system). However, a higher mean HScore was found in foreign patients (257 vs 222, p=0.02), in patients with concomitant infections with confirmed microbiological isolation (243 vs 214, p=0.022) and in those who required vital support (248 vs 212, p=0.004). Patients who died showed a higher mean HScore in comparison with survivors (241 vs 217, p=0.05). Conclusions Hemophagocytic syndrome is a life-threatening multisystemic disease that often requires vital support in intensive care units. Despite this and the use of a complex therapeutic approach, half of the patients died. We found higher HScores in patients presenting with a complicated HS (concomitant infections, need for vital support and death). The use of the new HScore as prognostic factor may help to identify patients with a poor outcome. Disclosure of Interest None declared

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender ( P < 0.001), fever ( P = 0.021), nephropathy ( P < 0.001), cutaneous vasculitis ( P = 0.023), positive anti-dsDNA antibodies ( P = 0.012) and cryoglobulinemia ( P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia ( P = 0.001) and antiphospholipid antibodies ( P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis ( P = 0.022), thrombocytopenia ( P = 0.004), lupus anticoagulant ( P = 0.013), positive IgM-aCL ( P = 0.039), positive ANA ( P = 0.002) and anti-dsDNA ( P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.

Objectives To analyze the efficacy and safety of treatment with belimumab, a monoclonal antibody that specifically binds the soluble form of the protein human B lymphocyte stimulator B (BLyS), in SLE patients refractory to standard treatment. Methods In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS registry, a multicenter study recruiting patients with refractory systemic autoimmune diseases treated with biological agents. Results On December 31, 2013, a total of 10 patients treated with belimumab were included in the BIOGEAS Registry, 9 females and 1 male, with a mean age of 41.8 years (range 24-71 years). These patients were heavily treated, with a mean of 7 years of corticosteroid treatment, antimalarials and at least one immunosuppressive agent, mycophenolate in 9, azathioprine in 7, metothrexate in 4, cyclosphosphamide in 2, cyclosporine A in 2, tacrolimus in 2 and talidomide in 2. Belimumab (10mg/kg) was administered in combination with corticosteroids (in all patients), antimalarials (6 patients) and immunosuppressive agents (8 patients, 6 with mycophenolate). The baseline average activity score (SELENA-SLEDAI) was 12 (range 6-33); 8 patients had high titers of anti-dsDNA and/or hypocomplementemia. Therapeutic indication included refractory mucocutaneous involvement (4 patients), refractory vasculitis (3 patients), systemic disease (2 patients) and refractory lupus nephritis (1 patient). After a mean follow-up of 7 months (range 2-12), clinical response could be evaluated in 9 patients, 8 classified as responders (improvement greater than 80% in 5 patients), while the remaining patient was classified as stable. Two patients (20%) developed adverse events (raised transaminases and systemic cryptococcosis due to severe CD4 lymphopenia); there were no deaths or lupus flares. Conclusions These postmarketing data in Spanish SLE patients in whom belimumab was used following the recommendations approved by the FDA/EMA (refractory disease to standard treatment, clinical and immunological active disease, SELENA-SLEDAI>6) have showed promising results, with a good therapeutic response and a safety profile similar to other biological therapies used off-label in patients with SLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5447

Background Kikuchi disease (KD) and systemic lupus erythematosus (SLE) share many clinical and histological features. The association of both entities has been reinforced over time with the publication of numerous case reports and small series (1). Some reviews about this topic were also published (2-3). However, no systematic review of the literature describing the characteristics of patients with KD and SLE has been performed to date. Objectives To describe the clinical, laboratory and outcome of reported cases of SLE in adult patients with KD. Methods We conducted a systematic literature review by searching through the databases MEDLINE (source: PubMed, 1996 to July 2011), EMBASE (1980 to July 2011) and Web of Science. The following terms were used: “Kikuchi”, “Lupus” and “Histiocytic necrotizing lymphadenitis” combining as MeSH terms and text words, without language restrictions. Studies were eligible when included adults (>14-years-age) and contained sufficient clinical and analytical data to establish whether the patient met the ACR criteria for SLE and if there was histological confirmation of KD diagnosis. Clinical, immunological and analytical variables were gathered. Results The search strategy yielded 115 papers of which 63 (54%) were excluded because insufficient data or because patients did not meet criteria for SLE. The article could not be recovered in 21 cases (18%). So, 67 patients with confirmed KD and definite SLE were included, of them 52 were women (female/male ratio 1:3.5). The mean age at KD diagnosis was 30 years (range 14-56). With respect to the time of diagnosis: SLE preceded KD in 10 (15%), was simultaneous with KD in 36 cases (54%), and after KD in 21 cases (31%). SLE was diagnosed an average of 23 months after KD (range 1-120), but in 45% of patients the diagnosis was made in the first year. The most frequent haematological abnormality was leukopenia in 75.5% of cases, especially at the expense of lymphopenia (75%), neutropenia was recorded in only 22% of patients. ANA (99%) and anti-DNA-native (60%) were the commonest auto-antibodies recorded, followed by anti-Ro (40%), anti-Sm (26%), anti-RNP (22%) and anti-cardiolipin (19%). Only 13% of SLE were diagnosed with lupus nephritis confirmed by renal biopsy (3 type II, 2 type III, 3 type 1 type IV and V). Conclusions Although most patients with KD and SLE were diagnosed simultaneously, one-third of SLE were developed after KD in some cases several years thereafter. Although 60% of SLE patients had anti-DNA native, only 13% of patients developed lupus nephritis. References Sopena B, Rivera A, Vazquez-Trinanes C, et al. Autoimmune manifestations of Kikuchi Disease. Semin Arthritis Rheum 2011; Dec 20 [Epub ahead of print]. Kucukardali Y, Solmazgul E, Kunter E, et al. Kikuchi-Fujimoto disease: analysis of 244 cases. Clin Rheumatol 2007; 26:50-4. Santana A, Lessa B, Galrao L, Lima I, Santiago M. Kikuchi-Fujimoto’s disease associated with systemic lupus erythematosus: case report and review of the literarture. Clin Rheumatol 2005; 24:60-3. Disclosure of Interest None Declared