Publications by authors named "Cesar Magro-Checa"

37 Publications

Different phenotypes of neuropsychiatric systemic lupus erythematosus are related to a distinct pattern of structural changes on brain MRI.

Eur Radiol 2021 Apr 30. Epub 2021 Apr 30.

Department of Radiology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.

Objectives: The underlying structural brain correlates of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) remain unclear, thus hindering correct diagnosis. We compared brain tissue volumes between a clinically well-defined cohort of patients with NPSLE and SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE). Within the NPSLE patients, we also examined differences between patients with two distinct disease phenotypes: ischemic and inflammatory.

Methods: In this prospective (May 2007 to April 2015) cohort study, we included 38 NPSLE patients (26 inflammatory and 12 ischemic) and 117 non-NPSLE patients. All patients underwent a 3-T brain MRI scan that was used to automatically determine white matter, grey matter, white matter hyperintensities (WMH) and total brain volumes. Group differences in brain tissue volumes were studied with linear regression analyses corrected for age, gender, and total intracranial volume and expressed as B values and 95% confidence intervals.

Results: NPSLE patients showed higher WMH volume compared to non-NPSLE patients (p = 0.004). NPSLE inflammatory patients showed lower total brain (p = 0.014) and white matter volumes (p = 0.020), and higher WMH volume (p = 0.002) compared to non-NPSLE patients. Additionally, NPSLE inflammatory patients showed lower white matter (p = 0.020) and total brain volumes (p = 0.038) compared to NPSLE ischemic patients.

Conclusion: We showed that different phenotypes of NPSLE were related to distinct patterns of underlying structural brain MRI changes. Especially the inflammatory phenotype of NPSLE was associated with the most pronounced brain volume changes, which might facilitate the diagnostic process in SLE patients with neuropsychiatric symptoms.

Key Points: • Neuropsychiatric systemic lupus erythematosus (NPSLE) patients showed a higher WMH volume compared to SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE). • NPSLE patients with inflammatory phenotype showed a lower total brain and white matter volume, and a higher volume of white matter hyperintensities, compared to non-NPSLE patients. • NPSLE patients with inflammatory phenotype showed lower white matter and total brain volumes compared to NPSLE patients with ischemic phenotype.
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http://dx.doi.org/10.1007/s00330-021-07970-2DOI Listing
April 2021

Quantitative susceptibility mapping in the thalamus and basal ganglia of systemic lupus erythematosus patients with neuropsychiatric complaints.

Neuroimage Clin 2021 22;30:102637. Epub 2021 Mar 22.

Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Systemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE (NPSLE), is not an exception. Current knowledge on underlying pathogenic mechanisms is incomplete, however, neuroinflammation is thought to play a critical role. Evidence from neurodegenerative diseases and multiple sclerosis suggests that neuroinflammation is correlated with brain iron accumulation, making quantitative susceptibility mapping (QSM) a potential hallmark for neuroinflammation in vivo. This study assessed susceptibility values of the thalamus and basal ganglia in (NP)SLE patients and further investigated the in vivo findings with histological analyses of postmortem brain tissue derived from SLE patients. We used a 3T MRI scanner to acquire single-echo T*-weighted images of 44 SLE patients and 20 age-matched healthy controls. Of the 44 patients with SLE, all had neuropsychiatric complaints, of which 29 were classified as non-NPSLE and 15 as NPSLE (seven as inflammatory NPSLE and eight as ischemic NPSLE). Mean susceptibility values of the thalamus, caudate nucleus, putamen, and globus pallidus were calculated. Formalin-fixed paraffin-embedded post-mortem brain tissue including the putamen and globus pallidus of three additional SLE patients was obtained and stained for iron, microglia and astrocytes. Susceptibility values of SLE patients and age-matched controls showed that iron levels in the thalamus and basal ganglia were not changed due to the disease. No subgroup of SLE showed higher susceptibility values. No correlation was found with disease activity or damage due to SLE. Histological examination of the post-mortem brain showed no increased iron accumulation. Our results suggest that neuroinflammation in NPSLE does not necessarily go hand in hand with iron accumulation, and that the inflammatory pathomechanism in SLE may differ from the one observed in neurodegenerative diseases and in multiple sclerosis.
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http://dx.doi.org/10.1016/j.nicl.2021.102637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053812PMC
July 2021

Hemocytometric characteristics of COVID-19 patients with and without cytokine Storm syndrome on the Sysmex XN-10 hematology analyzer.

Clin Chem Lab Med 2020 Dec 8. Epub 2020 Dec 8.

Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Heerlen & Sittard, The Netherlands.

Objectives: COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer.

Methods: From March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones.

Results: In addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS.

Conclusions: Hemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS.
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http://dx.doi.org/10.1515/cclm-2020-1529DOI Listing
December 2020

EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.

Ann Rheum Dis 2021 Feb 5. Epub 2021 Feb 5.

Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Department of Rheumatology, Université Paris-Saclay, Le Kremlin Bicêtre, France

Objectives: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies.

Methods: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting.

Results: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates.

Conclusions: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.
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http://dx.doi.org/10.1136/annrheumdis-2020-219724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871226PMC
February 2021

Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study.

Ann Rheum Dis 2020 09 20;79(9):1143-1151. Epub 2020 Jul 20.

Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands.

Objectives: To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.

Methods: From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2-5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.

Results: At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.

Conclusions: A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
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http://dx.doi.org/10.1136/annrheumdis-2020-218479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456552PMC
September 2020

Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome.

Eur J Case Rep Intern Med 2020 22;7(5):001675. Epub 2020 Apr 22.

Department of Rheumatology, Zuyderland Medical Center, Heerlen-Sittard, the Netherlands.

Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ). The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS.

Learning Points: Cytokine release syndrome may cause sudden and potentially life-threatening clinical deterioration in COVID-19 pneumonia, particularly in younger patients.Immunosuppressive therapy may provide important additional therapeutic benefit in these patients.Tocilizumab, a specific IL-6 inhibitor, led to dramatic clinical improvement in a young patient with severe COVID-19-associated cytokine release syndrome.
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http://dx.doi.org/10.12890/2020_001675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213824PMC
April 2020

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept.

PLoS One 2019 28;14(2):e0213073. Epub 2019 Feb 28.

Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213073PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395028PMC
December 2019

Laboratory and Neuroimaging Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: Where Do We Stand, Where To Go?

Front Med (Lausanne) 2018 4;5:340. Epub 2018 Dec 4.

Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Netherlands.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-systemic involvement. Nervous system involvement in SLE leads to a series of uncommon and heterogeneous neuropsychiatric (NP) manifestations. Current knowledge on the underlying pathogenic processes and their subsequent pathophysiological changes leading to NP-SLE manifestations is incomplete. Several putative laboratory biomarkers have been proposed as contributors to the genesis of SLE-related nervous system damage. Alongside the laboratory biomarkers, several neuroimaging tools have shown to reflect the nature of tissue microstructural damage associated with SLE, and thus were suggested to contribute to the understanding of the pathophysiological changes and subsequently help in clinical decision making. However, the number of useful biomarkers in NP-SLE in clinical practice is disconcertingly modest. In some cases it is not clear whether the biomarker is truly involved in pathogenesis, or the result of non-specific pathophysiological changes in the nervous system (e.g., neuroinflammation) or whether it is the consequence of a concomitant underlying abnormality related to SLE activity. In order to improve the diagnosis of NP-SLE and provide a better targeted care to these patients, there is still a need to develop and validate a range of biomarkers that reliably capture the different aspects of disease heterogeneity. This article critically reviews the current state of knowledge on laboratory and neuroimaging biomarkers in NP-SLE, discusses the factors that need to be addressed to make these biomarkers suitable for clinical application, and suggests potential future research paths to address important unmet needs in the NP-SLE field.
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http://dx.doi.org/10.3389/fmed.2018.00340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288259PMC
December 2018

Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.

PLoS One 2018 7;13(5):e0196793. Epub 2018 May 7.

Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigación Sanitaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937760PMC
July 2018

Protein array autoantibody profiles to determine diagnostic markers for neuropsychiatric systemic lupus erythematosus.

Rheumatology (Oxford) 2017 08;56(8):1407-1416

Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital Academic Medical Center.

Objective: The aim was to investigate the association between autoantibodies (autoAbs) and neuropsychiatric (NP) involvement in patients with SLE and to evaluate whether any autoAb or a combination of these autoAbs could indicate the underlying pathogenic process.

Methods: Using a multiplexed protein array for 94 antigens, we compared the serum autoAb profiles of 69 NPSLE patients, 203 SLE patients without NP involvement (non-NPSLE) and 51 healthy controls. Furthermore, we compared the profiles of NPSLE patients with clinical inflammatory (n = 38) and ischaemic (n = 31) NP involvement.

Results: In total, 75 IgG and 47 IgM autoAbs were associated with SLE patients in comparison with healthy controls. Comparing NPSLE with non-NPSLE and healthy control sera, 9 IgG (amyloid, cardiolipin, glycoprotein 2, glycoprotein 210, heparin, heparan sulphate, histone H2A, prothrombin protein and vimentin) and 12 IgM (amyloid, cardiolipin, centromere protein A, collagen II, histones H2A and H2B, heparan sulphate, heparin, mitochondrial 2, nuclear Mi-2, nucleoporin 62 and vimentin) autoAbs were present at significantly different levels in NPSLE. The combination of IgG autoAbs against heparan sulphate, histone H2B and vimentin could differentiate NPSLE from non-NPSLE (area under the curve 0.845, 99.97% CI: 0.756, 0.933; P < 0.0001). Compared with non-NPSLE, four IgG and seven IgM autoAbs were significantly associated with inflammatory NPSLE. In ischaemic NPSLE, three IgG and three IgM autoAbs were significantly different from non-NPSLE patients.

Conclusion: In our cohort, the presence of high levels of anti-heparan sulphate and anti-histone H2B combined with low levels of anti-vimentin IgG autoAbs is highly suggestive of NPSLE. These results need to be validated in external cohorts.
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http://dx.doi.org/10.1093/rheumatology/kex073DOI Listing
August 2017

Value of multidisciplinary reassessment in attribution of neuropsychiatric events to systemic lupus erythematosus: prospective data from the Leiden NPSLE cohort.

Rheumatology (Oxford) 2017 10;56(10):1676-1683

Department of Rheumatology, Leiden University Medical Center, Leiden.

Objective: To determine the contribution of reassessment in the attribution process of neuropsychiatric (NP) events to SLE or other aetiologies in a large, prospective and multidisciplinary assessed NPSLE cohort and to compare these results with other available attribution models for NP events occurring in SLE.

Methods: Three hundred and four consecutive SLE patients presenting NP events were evaluated. All subjects underwent standardized multidisciplinary medical, neuropsychological, laboratory and radiological examination on the inclusion and reassessment dates. Diagnosis was always established by multidisciplinary consensus. The final diagnosis after reassessment also took into account disease course and response to treatment. These data were compared with currently available attribution models for NP events in SLE.

Results: A total of 463 NP events were established. After reassessment, attribution to SLE was discordant in 64 (13.8%) NP events when compared with the first visit. We show that 14.5% of NP events previously attributed to SLE reclassified as non-NPSLE. In 86.4% of these patients immunosuppressive therapy was started after the first visit. When reassessment and available attribution models were compared, NPSLE cases overlapped considerably. Although specificity was high for all comparisons (0.81-0.95), an important variation in sensitivity (0.39-0.83) and agreement estimates (κ = 0.29-0.68) was observed. The Italian algorithm showed the highest sensitivity and specificity (>0.80) and moderate agreement (0.59-0.64).

Conclusion: In clinical practice NP events presenting in SLE are too often attributed to an immune-mediated origin. Multidisciplinary reassessment avoids misclassification in NPSLE. Multidisciplinary reassessment is the reference standard in NP events presenting in SLE and cannot be replaced by available attribution models.
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http://dx.doi.org/10.1093/rheumatology/kex019DOI Listing
October 2017

C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus.

Front Immunol 2016 27;7:647. Epub 2016 Dec 27.

Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.

C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE.
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http://dx.doi.org/10.3389/fimmu.2016.00647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5186770PMC
December 2016

Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.

Arthritis Res Ther 2016 12 3;18(1):289. Epub 2016 Dec 3.

Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.

Methods: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.

Results: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.

Conclusions: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.
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http://dx.doi.org/10.1186/s13075-016-1192-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135817PMC
December 2016

Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies.

Arthritis Rheumatol 2016 09;68(9):2338-44

Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy.

Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.

Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10(-6) ) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined  = 3.29 × 10(-12) ). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors.

Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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http://dx.doi.org/10.1002/art.39730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530728PMC
September 2016

Glial and axonal changes in systemic lupus erythematosus measured with diffusion of intracellular metabolites.

Brain 2016 05 11;139(Pt 5):1447-57. Epub 2016 Mar 11.

C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

Systemic lupus erythematosus is an inflammatory autoimmune disease with multi-organ involvement. Central nervous system involvement in systemic lupus erythematosus is common and results in several neurological and psychiatric symptoms that are poorly linked to standard magnetic resonance imaging outcome. Magnetic resonance imaging methods sensitive to tissue microstructural changes, such as diffusion tensor imaging and magnetization transfer imaging, show some correlation with neuropsychiatric systemic lupus erythematosus (NPSLE) symptoms. Histological examination of NPSLE brains reveals presence of cerebral oedema, loss of neurons and myelinated axons, microglial proliferation and reactive astrocytosis, microinfacrts and diffuse ischaemic changes, all of which can affect both diffusion tensor imaging and magnetization transfer imaging in a non-specific manner. Here we investigated the underlying cell-type specific microstructural alterations in the brain of patients with systemic lupus erythematosus with and without a history of central nervous system involvement. We did so combining diffusion tensor imaging with diffusion-weighted magnetic resonance spectroscopy, a powerful tool capable of characterizing cell-specific cytomorphological changes based on diffusion of intracellular metabolites. We used a 7 T magnetic resonance imaging scanner to acquire T1-weighted images, diffusion tensor imaging datasets, and single volume diffusion-weighted magnetic resonance spectroscopy data from the anterior body of the corpus callosum of 13 patients with systemic lupus erythematosus with past NPSLE, 16 patients with systemic lupus erythematosus without past NPSLE, and 19 healthy control subjects. Group comparisons were made between patients with systemic lupus erythematosus with/without past NPSLE and healthy controls on diffusion tensor imaging metrics and on diffusion coefficients of three brain metabolites: the exclusively neuronal/axonal N-acetylaspartate, and the predominantly glial creatine + phosphocreatine and choline compounds. In patients with systemic lupus erythematosus with past NPSLE, significantly higher diffusion tensor imaging mean and radial diffusivities were accompanied by a significantly higher intracellular diffusion of total creatine (0.202 ± 0.032 μm(2)/ms, P = 0.018) and total choline (0.142 ± 0.031 μm(2)/ms, P = 0.044) compared to healthy controls (0.171 ± 0.024 μm(2)/ms, 0.124 ± 0.018 μm(2)/ms, respectively). Total N-acetylaspartate, total creatine and total choline diffusion values from all patients with systemic lupus erythematosus correlated positively with systemic lupus erythematosus disease activity index score (P = 0.033, P = 0.040, P = 0.008, respectively). Our results indicate that intracellular alterations, and in particular changes in glia, as evidenced by increase in the average diffusivities of total choline and total creatine, correlate with systemic lupus erythematosus activity. The higher diffusivity of total creatine and total choline in patients with NPSLE, as well as the positive correlation of these diffusivities with the systemic lupus erythematosus disease activity index are in line with cytomorphological changes in reactive glia, suggesting that the diffusivities of choline compounds and of total creatine are potentially unique markers for glial reactivity in response to inflammation.
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http://dx.doi.org/10.1093/brain/aww031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006250PMC
May 2016

Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus.

Arthritis Rheumatol 2016 08;68(8):1945-54

Leiden University Medical Center, Leiden, The Netherlands.

Objective: To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome.

Methods: Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non-SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated.

Results: Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLE-related NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved.

Conclusion: Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment.
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http://dx.doi.org/10.1002/art.39653DOI Listing
August 2016

Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives.

Drugs 2016 Mar;76(4):459-83

Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.
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http://dx.doi.org/10.1007/s40265-015-0534-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791452PMC
March 2016

A multimodal MRI approach to identify and characterize microstructural brain changes in neuropsychiatric systemic lupus erythematosus.

Neuroimage Clin 2015 16;8:337-44. Epub 2015 May 16.

C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.
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http://dx.doi.org/10.1016/j.nicl.2015.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474280PMC
April 2016

Morphea-like plaques, induration of the extremities, and eosinophilia.

Cleve Clin J Med 2015 May;82(5):283-4

Department of Rheumatology, San Cecilio University Hospital, Granada, Spain.

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http://dx.doi.org/10.3949/ccjm.82a.13126DOI Listing
May 2015

Drug survival of anti-tumour necrosis factor α therapy in spondyloarthropathies: results from the Spanish emAR II Study.

Rheumatology (Oxford) 2015 Aug 12;54(8):1459-63. Epub 2015 Mar 12.

Rheumatology Department, San Cecilio University Hospital, Granada, Spain.

Objective: To assess drug survival and the reasons for switching anti-TNF-α therapy in SpA patients in a Spanish nationwide study.

Methods: A cross-sectional study was performed. Sample size was calculated to represent all regions and hospitals throughout the country. Demographic data, patient characteristics and disease activity parameters were obtained. Drug survival and reasons for switching anti-TNF therapy were also recorded.

Results: A total of 467 SpA patients receiving at least one anti-TNF agent were identified. Among patients who received a first, second and third anti-TNF course, 39.4%, 37.4% and 23.1% discontinued treatment, respectively. The main reasons for switching anti-TNF agents in the first course were lack or loss of efficacy (LOE) and adverse events (AEs) in 40% and 30% of switchers, respectively. Similarly, reasons for switching during the second anti-TNF course were LOE in 48% and AEs in 28% of switchers. Of the 467 SpA patients starting anti-TNF therapy, 28% switched to a second and 8% switched to a third therapy. Mean drug survival for the first, second and third anti-TNF courses were 84.4 (95% CI 78.4, 90.5), 70.2 (95% CI 61.6, 78.9) and 64.8 (95% CI 51.1, 78.5) months, respectively (P = 0.315).

Conclusion: Twenty-eight per cent of SpA patients starting anti-TNF therapy switched to a second anti-TNF agent. Drug survival did not differ among anti-TNF courses. The main reason for switching anti-TNF therapy was LOE. Switchers were more frequently women and had higher disease activity parameters at the time of the study than non-switchers.
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http://dx.doi.org/10.1093/rheumatology/kev001DOI Listing
August 2015

Cluster analysis of an array of autoantibodies in neuropsychiatric systemic lupus erythematosus.

J Rheumatol 2014 Aug;41(8):1720-1

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands;

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http://dx.doi.org/10.3899/jrheum.140027DOI Listing
August 2014

Calcium pyrophosphate crystal deposition disease: diagnosis and treatment.

Open Access Rheumatol 2014 8;6:39-47. Epub 2014 May 8.

Rheumatology Department, San Cecilio University Hospital, Granada, Spain.

Calcium pyrophosphate dihydrate crystal deposition disease (CPPD) is an inflammatory arthritis produced by the deposition of calcium pyrophosphate (CPP) crystals in the synovium and periarticular soft tissues. It is the third most common inflammatory arthritis. Diagnosis is suspected on the basis of the clinical picture and radiographic/laboratory findings. The reference standard for the diagnosis of CPPD is based on the identification of CPP crystals in synovial fluid by light microscopy, compensated polarized light microscopy, or phase contrast microscopy. Most treatment approaches for CPPD are based upon clinical experience and not upon controlled trials. They range - depending on the subtype and the characteristics of symptoms - from no treatment to interleukin-1 blockade antibodies or specific therapy for an underlying disease. This review summarizes all we know so far about the diagnosis and management of CPPD.
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http://dx.doi.org/10.2147/OARRR.S39039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045115PMC
May 2014

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

Ann Rheum Dis 2015 Mar 17;74(3):e14. Epub 2014 Feb 17.

Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1136/annrheumdis-2013-204909DOI Listing
March 2015

Vitamin D insufficiency is associated with higher carotid intima-media thickness in psoriatic patients.

Eur J Dermatol 2014 Jan-Feb;24(1):53-62

Dermatology Department,, School of Medicine.

Background: Psoriasis has been associated with vitamin D insufficiency and cardiovascular risk factors. Reports show that serum 25-hydroxyvitamin D (25-OHD) levels are inversely associated with chronic inflammatory systemic diseases, cardiovascular risk factors and cardiovascular outcomes.

Objective: To analyze the association between 25-hydroxyvitamin D serum levels and subclinical carotid atherosclerosis (maximal intima-media thickness (MIMT)) in psoriasis patients and controls. MIMT was compared and associated factors were analyzed.

Patients And Method: This was a case-control study with 44 psoriatic patients without arthritis from a Dermatology outpatient clinic in Granada (Spain) and 44 controls. Confounding factors related to 25-OHD serum levels and cardiovascular risk factors were also analyzed.

Results: 25-OHD levels were significantly lower in the psoriatic than in the control group (29.20 vs. 38.00 ng/mL p<0.0001) and a significant negative correlation was found between serum 25-OHD levels and the MIMT (rs=-0.678, p<0.0001) in psoriatic patients. No correlation was found in healthy controls. This association remained after adjusting for confounders. Serum 25-OHD levels were significantly lower (p=0.003) in psoriatic patients with carotid atheromatous plaque (22.38±10.23 ng/mL) than in those without (31.74±8.62 ng/mL). Patients with a longer history of psoriasis presented significantly higher MIMT than controls (638.70±76.21 vs 594.67±80.20 μm; p=0.026 for ≥6 yrs with psoriasis).

Conclusions: In psoriasis patients, lower serum 25-OHD levels were associated with higher MIMT after adjusting for selected confounding factors. The MIMT risk increases with a longer history of psoriasis, regardless of the patient's age.
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http://dx.doi.org/10.1684/ejd.2013.2241DOI Listing
February 2015

Demyelinating disease in SLE: is it multiple sclerosis or lupus?

Best Pract Res Clin Rheumatol 2013 Jun;27(3):405-24

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Among the 12 systemic lupus erythematosus (SLE)-related central nervous system (CNS) syndromes defined by the American College of Rheumatology (ACR), demyelinating syndrome and myelopathy are two of the less prevalent and more poorly understood ones. One important issue concerning demyelinating disease in SLE is that it can be easily misdiagnosed with other central nervous system demyelinating disorders such as multiple sclerosis (MS). A clinically isolated neurological syndrome can be the presenting feature before other concomitant symptoms of SLE appear or definite MS is diagnosed. Although challenging, some diagnostic tests used in clinical practice and research may help to differentiate between these entities. These tests have improved the understanding of the pathogenesis in these diseases, but some points, such as the role of antiphospholipid antibodies in SLE-associated transverse myelitis, remain unclear and are a matter of ongoing debate. This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse myelitis, optic neuritis and neuromyelitis optica.
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http://dx.doi.org/10.1016/j.berh.2013.07.010DOI Listing
June 2013

Association of 25-hydroxyvitamin D serum levels and metabolic parameters in psoriatic patients with and without arthritis.

J Am Acad Dermatol 2013 Dec 3;69(6):938-46. Epub 2013 Oct 3.

Dermatology Department, San Cecilio University Hospital, Granada, Spain.

Background: Psoriasis has been related to a higher prevalence of cardiovascular risk factors. Vitamin-D deficiency has been associated with metabolic syndrome, cardiovascular disease, and psoriasis. However, there has been no comparative study on the effects of vitamin-D status between patients with and without psoriatic arthritis.

Objective: The objective was to assess the relationship of 25-hydroxyvitamin D [25-(OH)D] levels with lipid and glucose metabolism parameters in psoriatic patients with and without arthritis.

Methods: We studied 122 patients with psoriasis (61 without arthritis and 61 with arthritis) from the psoriasis unit (dermatology department) and rheumatology department of our hospital, analyzing lipid and glucose metabolism variables and serum 25-(OH)D concentrations. Measurements were conducted within a 2-month period to minimize seasonal bias in 25-(OH)D levels.

Results: In the psoriatic patients without arthritis, serum 25-(OH)D levels were inversely correlated with fasting glucose (r = -0.285; P = .026), total cholesterol (r = -0.440; P = .000), low-density lipoprotein (r = -0.415; P = .001), total cholesterol/high-density lipoprotein (r = -0.303; P = .01), and triglyceride (r = -0.280; P = .029) values. This association remained statistically significant for glucose, total cholesterol, and low-density lipoprotein after controlling for confounding factors in multivariate analysis. No association was found between serum 25-(OH)D levels and any metabolic parameter in the patients with psoriatic arthritis.

Limitations: This is a cross-sectional study that supports the hypothesis of an association between vitamin D and metabolic parameters but does not establish a causal relationship.

Conclusions: Serum 25-(OH)D was inversely related to lipid and glucose metabolism parameters in psoriatic patients without arthritis, whereas no such association was observed in psoriatic patients with arthritis. Interventional studies are warranted to assess the effects of vitamin-D supplements on the metabolic profile of psoriatic patients without arthritis.
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http://dx.doi.org/10.1016/j.jaad.2013.08.007DOI Listing
December 2013

Association of 25-hydroxyvitamin D with metabolic syndrome in patients with psoriasis: a case-control study.

Acta Derm Venereol 2014 Mar;94(2):142-5

Department of Dermatology, San Cecilio University Hospital, ES-18012 Granada, Spain.

Vitamin D deficiency is associated with higher cardiovascular risk and metabolic syndrome (MeS) criteria. The main objective of this study was to analyse the association of 25-hydroxyvitamin D (25-OHD) serum levels with MeS (National Cholesterol Education Program-Adult Treatment Panel-III criteria) in 46 Spanish patients with psoriasis, but without arthritis and systemic treatment, and 46 control subjects, matched by sex and age. The patients with psoriasis showed significantly lower level of 25-OHD than controls (30.5 vs. 38.3 ng/ml; p = 0.0001). Patients with MeS had significantly lower serum levels of 25-OHD than those without MeS (24.1 ± 7.5 vs. 32.8 ± 8.9, p = 0.007), and a negative correlation was found between 25-OHD and waist circumference, diastolic blood pressure, fasting glucose, and triglyceridaemia. In the control group no significant correlation between 25-OHD and MeS was found. Al-though the sample was small, our results suggest a potential protective role for 25-OHD in the metabolic profile of patients with psoriasis without arthritis.
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http://dx.doi.org/10.2340/00015555-1642DOI Listing
March 2014

Cardiovascular risk assessment according to a national calibrated score risk index in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors.

Joint Bone Spine 2014 Mar 9;81(2):164-8. Epub 2013 Aug 9.

Rheumatology Division, Hospital Universitario San Cecilio, Granada, Spain.

Objective: To assess cardiovascular (CV) risk in psoriatic arthritis (PsA) patients without clinically evident CV disease or classic atherosclerosis risk factors according to the SCORE chart following the EULAR recommendations.

Methods: Eighty PsA patients without previous CV events or atherosclerosis risk factors and eighty matched controls were included. Information on demographic, anthropometric and clinical-serological data of disease was assessed. The national calibrated Systematic Coronary Risk Evaluation (SCORE) index was calculated and the association between this SCORE and clinical-serological data of these patients was analyzed.

Results: PsA patients had higher acute phase reactants as well as higher SCORE mean values than healthy controls (1.99±3.52 vs. 1.0±1.74; P=0.028). According to SCORE definitions, 71 (89%) patients had low-intermediate CV risk and 9 (11%) were above the threshold of high risk. In the control group, 76 (95%) had low-intermediate risk and four (5%) had high CV risk. However, there were no differences in CV risk stratification between both groups (P=0.148). PsA patients with high-very high CV risk had longer disease duration (P=0.001) and higher levels of triglycerides (P=0.009). PsA patients showed a significant correlation between SCORE values and disease duration (β=0.185; P=0.0001) and the average annual levels of C reactive protein (CRPa), β=2.38; P=0.014.

Conclusion: CV risk assessment in PsA patients without clinically evident CV disease or classic atherosclerosis risk factors may be underestimated by using only the SCORE chart. In these patients, disease duration and the CRPa may help to establish a better stratification of the actual CV risk.
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http://dx.doi.org/10.1016/j.jbspin.2013.07.008DOI Listing
March 2014
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