[Mesenteric panniculitis]. / Paniculitis mesentérica.

Mesenteric panniculitis is a condition characterized by chronic nonspecific inflammation of the mesentery. There is little and often confusing information about its characteristics and the approach to take once it has been demonstrated by an imaging test. We propose to describe the epidemiological, clinical, laboratory, radiological and pathological features of the patients with mesenteric panniculitis reported in the literature, as well as possible disorders causal or associated with mesenteric panniculitis, in the opinion of the authors of each study. Finally, we will review the different therapeutic options used and the response to them. To that end a literature search was performed from the main medical databases selecting ítems with information on these aspects. This information was collected on a database stored in SPSS software for further analysis and summary.

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.

OBJECTIVES: To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. METHODS: Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. RESULTS: Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. CONCLUSIONS: These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.

Influence of psychological stress on headache in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the prevalence and disability of headache in patients with systemic lupus erythematosus (SLE) with the general population and to assess the role of chronic psychological stress (CPS) in headache development. METHODS: One hundred seventy patients with SLE and 102 control subjects matched for age, sex, and level of education were included in this multicenter, cross-sectional study. CPS, headache-related disability, and chronic analgesic intake (CAI) were evaluated in all participants. RESULTS: No statistical differences in the prevalence of headache between both groups were observed but headache disability was significantly higher in patients with SLE. In addition, a higher average score in the Cohen Perceived Stress Scale (CPSS) and a higher prevalence of patients with CAI were observed in patients with SLE. In multivariate analysis, CPSS score was positively (OR 1.09; 95% CI: 1.03-1.14; p = 0.001) and CAI negatively (OR 0.43; 95% CI: 0.19-0.99; p = 0.049) associated with headache in patients with SLE. CONCLUSION: Despite the prevalence of headache in patients with SLE and the general population being similar, headache-related disability may be higher in patients with SLE. Moreover, CPS might play a role in the pathogenesis of SLE headache, whereas CAI might have a protective effect against it.

Health-related internet use by lupus patients in southern Spain.

Internet has become a widely used tool by patients seeking information on different diseases. The information regarding lupus patients' Internet use is scarce. This study aims to explore the attitudes and practices of lupus patients in southern Spain, regarding Internet use to find health-related information. A survey was carried out including 150 patients from six Andalusian Hospitals. To search for information, 67.3 % of the patients used Internet. The proportion of female Internet users was higher (69.3 vs 46.2 %), particularly those belonging to a patients' association (81.8 vs 32.7 %), and are regular users of Internet (80.2 vs 44.4 %); 37.5 % thought the information found in the Internet was of little use or not useful at all, and 58 % of the respondents stated that the information found caused them concern while for 27 %, it was a relief. Most patients preferred the information given by their physicians (63.6 %); 33.9 % considered that the information from both sources was complementary, and 2.5 % preferred the information obtained from the Internet. A percentage of 85.3 of the patients would like their physicians to provide them with information on high-quality sites regarding their illness. Lupus patients make frequent use of the Internet to look for information on their disease. Considering this, and because better-informed patients follow more precisely the indications given by the physician, medical staff should collaborate in the development of high-quality sites for the patient to have additional sources of information.

IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.

To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

Livedo racemosa como signo de presentación de un síndrome antifosfolípido secundario a lupus eritematoso sistémico / Livedo racemosa as a presenting sign of antiphospholipid syndrome secondary to systemic lupus erythematosus

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Association between -174 interleukin-6 gene polymorphism and biological response to rituximab in several systemic autoimmune diseases.

Rituximab has become a pivotal treatment for systemic autoimmune diseases. The aim of this study was to determine whether the genetic variant -174 IL-6 contributes to differences in the response to rituximab in patients with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory myopathies, anti-neutrophil cytoplasmic antibody-mediated vasculitis, systemic sclerosis, Sjöegren's syndrome, rheumatoid arthritis, and autoimmune hemolytic anemia. DNA samples from 144 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for -174 IL-6 (rs1800795) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after the first infusion with rituximab, we evaluated the response to the drug: 60.4% of the patients showed a complete response, partial 27.8%, and 11.8% did not respond to the treatment. The CC genotype frequency was significantly increased in nonresponders with respect to responders (23.5% vs. 7.1%, respectively; p=0.049; odds ratio (OR)=4.03, 95% confidence intervals (CI) 0.78-16.97). According to the genotype distribution, rituximab was effective in 69.2% of the CC carriers, 91.9% of the CG carriers, and 88.4% of the GG carriers. A similar trend was observed when SLE patients were analyzed separately (27.3% carried CC homozygosis in nonresponders and 6.9% in responders; p=0.066; OR=5.10, 95% CI 0.65-31.73). Rituximab was effective in 62.5% of the CC carriers, 88.9% of the GC carriers, and 90% of the GG carriers. These results suggest that -174 IL-6 (rs1800795) gene polymorphism plays a role in the response to rituximab in systemic autoimmune diseases. Validation of these findings in independent cohorts is warranted.

Registry of the Spanish network for systemic sclerosis: clinical pattern according to cutaneous subsets and immunological status.

OBJECTIVE: To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis. METHODS: We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P < 0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P < 0.05), and sicca syndrome (37.5% vs 14.5%, P < 0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor. CONCLUSIONS: The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements.

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial.

BACKGROUND: Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. METHODS: A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. RESULTS: The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. CONCLUSIONS: Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.

A 3'-untranslated region variant is associated with impaired expression of CD226 in T and natural killer T cells and is associated with susceptibility to systemic lupus erythematosus.

OBJECTIVE: Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association. METHODS: Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments. RESULTS: A 3-variant haplotype, rs763361;rs34794968;rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 × 10(-4) , odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts. CONCLUSION: This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells.

Anti-cofactor autoantibodies in systemic lupus erythematosus: prevalence, clinical and HLA class II associations.

The aim of our study was to evaluate the clinical and HLA-class II allele associations of some anti-cofactor antibodies in a homogeneous group of European patients with SLE. One hundred thirty-six patients with SLE, fulfilling four or more of the ACR 1997 revised criteria for the classification of the disease, coming from 7 European countries, were enrolled consecutively. Anti-prothrombin (anti-PT), anti-annexin V (anti-AnnV), anti-protein C (anti-Cprot) and anti-protein S (anti-Sprot) were determined by using commercial ELISA kits. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 loci was performed by using PCR-SSOP method, carried out using digoxygenin (DIG) labeled probes. The prevalence of anti-AnnV, anti-PT, anti-Cprot and anti-Sprot was 19%, 10.4%, 4.4% and 8.1%, respectively. Twenty-seven % of anti-AnnV positive patients reported migraine vs 5.5% of anti-AnnV negatives (p = 0.003, but p not significant, odds ratio (OR) = 6.4, 95% confidence interval (CI) = 2-21). Anti-PT, anti-AnnV and anti-Sprot were positively associated with some HLA alleles, but pc was not significant. In this study we have shown that some HLA alleles carry the risk to produce antibodies against phospholipid-binding proteins, but these association need confirmation in other studies, because they have never been reported and appear to be weak associations.

Patient satisfaction with nursing care in a regional university hospital in southern Spain.

Patient satisfaction is a valid indicator for measurement of service quality. Patients' opinions are important because dissatisfaction suggests opportunities for improvement. We evaluated the satisfaction of patients with nursing care in a regional university hospital in southern Spain and determined the relevant sociodemographic and attendance characteristics. A cross-sectional descriptive study was undertaken using the SERVQUAL questionnaire. Reliability and validity of the SERVQUAL instrument were established. The only interaction considered was gender and education level. Analysis of covariance showed that the only factors significantly associated with lower patient satisfaction were female gender, higher educational level, lower overall satisfaction with the hospital, and not knowing the name of the nurse.

Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial.

OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

[Clinical and immunological features in 112 patients with antiphospholipid syndrome]. / Manifestaciones clínicas y alteraciones inmunológicas en pacientes con síndrome antifosfolipídico. Presentación de 112 casos.

BACKGROUND AND OBJECTIVE: We decided to describe the demographic, clinical and laboratory characteristics of a series of patients with antiphospholipid syndrome (APS) (Harris criteria) and review other Spanish published series. PATIENTS AND METHOD: We describe 112 patients with APS, 50 primary (PAPS) and 62 secondary (SAPS) -56 (90%) to systemic lupus erythematosus (SLE)-, monitorized in two referral centers in Malaga (Spain) from 1989 to 2000. All data were obtained from the medical records by means of a protocol. RESULTS: The age was similar in both groups (42.3 [14.7] years for the whole series). Patients with SAPS had an earlier onset of the disease (29.6 [12.6] years, vs 37.0 [13.9] years in PAPS) and they had a longer evolution of the disease (143.3 [115.5] months, vs 83.5 [73.5] months in PAPS). There was a female predominance (84% and 60% in SAPS and PAPS, respectively). The prevalences of arterial (43%) and venous thrombosis (39%), fetal loss (40%), premature births (9%), anticardiolipin antibodies (88%) and lupus anticoagulant (54%) were similar in both groups. The prevalence of ANA-IFI, thrombocytopenia and autoimmune anemia was higher in SAPS. CONCLUSIONS: Patients with PAPS and SAPS did not present any differences in the clinical manifestations and immunological disorders of the syndrome. Those patients with SAPS were younger at the beginning of the disease and there was a female predominance. Our patients were different from those included in other Spanish published series, which could be explained by selection and classification bias.