2019/2020
Maria Adriana Grilo Mendes
Lipid metabolism and disease activity in juvenile Systemic Lupus Erythematosus Metabolismo lipídico e atividade de doença no Lupus Eritematoso
Sistémico juvenil
Mestrado Integrado em Medicina
Área: Reumatologia Tipologia: Dissertação
Trabalho efetuado sob a Orientação de: Doutora Iva Brito
Trabalho organizado de acordo com as normas da revista: Acta Reumatológica Portuguesa
Maria Adriana Grilo Mendes
Lipid metabolism and disease activity in juvenile Systemic Lupus Erythematosus Metabolismo lipídico e atividade de doença no Lupus Eritematoso
Sistémico juvenil
Aos meus pais, irmãos e Ahmed.
Lipid metabolism and disease activity in
juvenile Systemic Lupus Erythematosus
Sara Ganhão1, Adriana Mendes2, Francisca Aguiar3, Mariana Rodrigues3, Iva Brito2, 3 1Centro Hospitalar e Universitário de São João, Rheumatology, Oporto, Portugal, 2Faculty of Medicine of Oporto's University, Oporto, Portugal, 3Centro Hospitalar e Universitário de São João, Young Adult and Pediatric Rheumatology Unit, Oporto, Portugal Corresponding author information’s: Maria Adriana Grilo Mendes Faculdade de Medicina da Universidade do Porto Alameda Professor Hernâni Monteiro 4200-319 Porto adrianagrilomendes@gmail.com
Abstract
Objective: To assess the relationship between lipid profile and disease activity in juvenile Systemic Lupus Erythematosus (jSLE) patients.Material and Methods: Retrospective study of jSLE patients (2012 to 2019
EULAR/ACR classification criteria for Systemic Lupus Erythematosus (SLE)). Juvenile-onset was defined as age at diagnosis £18 years. Demographic and clinical characteristics were collected: age of the patient at diagnosis and at the time of the last hospital visit and sex; laboratorial study with Sedimentation Rate, C-Reactive Protein, Albumin, Creatinine, Complement (C3 and C4), antibodies related to LES and lipid profile; urinalyses; clinical manifestations and patient’s medication. To evaluate the activity of jSLE, the Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) was used. The statistical analysis was performed using the software SPSS 22.0. Spearman’s rank non-parametric test, Pearson’s parametric test, T-test and Mann-Whitney test were used. P value < 0.05 was considered significant for all the statistical tests.
Results: 35 patients were included (91.4% female). The current median age and
the average age at diagnosis of the patients were 22 (16-35) and 15.8 (2.4) years, respectively. Total cholesterol was negatively correlated with serum albumin (p= 0.043, rho=-0.378) and positively with SLEDAI (p=0.032; rho= 0.392), proteinuria (p=0.009; rho= 0.469) and leukocyturia (p=0.031; rho= 0.394). A positive correlation was found between LDL cholesterol and proteinuria (p=0.043; rho= 0.385). Triglycerides were positively correlated with C-Reactive Protein (p=0.001; rho= 0.575) and prednisolone daily dose (p=0.035; rho= 0.394). HDL cholesterol correlated positively with proteinuria (p=0.026, rho= 0.407) and serum creatinine (p= 0.045, rho= 0.369). Mean LDL cholesterol was higher in anti-Sm positive patients (p=0.022). No differences were found regarding anti-phospholipids antibodies.
Conclusion: In our LESj patients group an increased expression of total
cholesterol, LDL cholesterol, HDL cholesterol and triglycerides is associated with disease activity. High doses of corticotherapy is also associated with worse lipid profile. Keywords: Systemic Lupus Erythematosus; Juvenile-onset; Dyslipidemia; Atherosclerosis
Introduction:
Systemic Lupus Erythematosus (SLE) is a chronic, multisystemic, auto-immune disease caused by autoantibodies against nuclear and cytoplasmic antigens and is characterized by periods of remission and exacerbation1.
Juvenile Systemic Lupus Erythematosus (jSLE) corresponds to 15% of cases of SLE and is defined as disease onset before 18 years2. The jSLE cases, when compared to SLE with adult-onset, have a more severe clinical phenotype, higher prevalence of organ damage at diagnosis, worse outcomes and lower life expectancy3,4.
When compared to the general population, patients with SLE have higher morbidity and mortality rates. The major causes of death in SLE are infection, lupus nephritis and cardiovascular diseases5.
Regarding cardiovascular morbidity, and after adjusting for traditional cardiovascular risk factors, SLE patients have a 5-10 times higher risk of myocardial infarction when compared to age and sex matched controls6. In fact, rates of myocardial infarctions in women with SLE are up to 50 fold higher than in women without SLE7.
It is possible that SLE pathophysiology, namely the immune dysregulation, has a crucial role in vascular damage and accelerated formation of atherosclerotic plaques6. On the other hand, prevalence of traditional cardiovascular risk factors such as dyslipidemia is higher in SLE patients7. Children and adolescents with SLE, prolonged exposure to risk factors, may be at higher risk for premature atherosclerotic disease8.
The “lupus pattern” of dyslipoproteinemia has been characterized by increased levels of very low-density lipoproteins (VLDL) and triglycerides (TG) and lower levels of high-density lipoprotein cholesterol (HDL)9. These lipid profile alterations can help explain the underlying pathogenesis mechanisms in SLE and discover new diagnosis and treatment targets10. In addition, drugs used in SLE also have an influence in the patients’ lipid profile5. The aim of the study is to assess the relationship between the lipid profile and disease activity in jSLE patients.
Methods
1. Population This retrospective study evaluated 35 jSLE patients diagnosed according to the 2012 and 2019 EULAR/ACR (European League Against Rheumatism and American College of Rheumatology) classification criteria for SLE11. All these patients were treated at the Centro Hospitalar e Universitário de São João, Young Adult and Pediatric Rheumatology Unit. 2. Demographic and clinical data: Juvenile-onset was defined as age at diagnosis £18 anos. The data was obtained from the patient’s medical records with the authorization of the hospital’s ethics commission.2.1 Demographic data: patient’s age at diagnosis and in the last medical visit; patients’ gender.
2.2 Clinical manifestations: The presence of clinical manifestations (musculoskeletal, mucocutaneous, renal, pulmonary, hematological and serosal) was evaluated.
2.3 Clinical analysis: Laboratorial results: total cholesterol (TC), low-density lipoproteins (LDL) cholesterol, high-density lipoproteins (HDL) cholesterol, triglycerides (TG), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), serum albumin, serum creatinine, anti-double stranded DNA antibodies (dsDNA), Antinuclear antibodies (ANA), antinucleosome antibodies, anti-ribosomal P protein antibodies, anti-Sm antibodies, antibodies against B2-glycoprotein I, anti-cardiolipin antibodies, lupus anticoagulant, anti-SSA antibodies, anti-SSB antibodies and Complement components 3 and 4 (C3 and C4). Proteinuria, leukocyturia and erythrocyturia were evaluated through urinalysis.
Erythematosus Disease Activity Index-2K (SLEDAI-2K)12. Lupus low disease activity (LLDA) was defined as SLEDAI-2K£ 4 with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity13.
2.5 Medication: Assessment of prescription of the following drugs and dosages- Prednisolone, hydroxychloroquine, mychophenolate mophetil and azathioprine 2.6 Statistical analysis: The statistical analysis was performed using the software SPSS 22.0. The categorical variables were described in absolute values (n) and the proportions in percentages (%). The Pearson’s parametric test and the Spearman’s rank non-parametric test were used to evaluate the relationship between clinical continuous variables and the lipid parameters. The T-test and the Mann-Whitney’s test were used to evaluate relationships between categorical variables of disease activity and patient’s treatment and the lipid parameters with and without normal distribution, respectively. P value < 0.05 was considered significant for all the statistical tests.
Results
Table I represents the clinical and demographic characteristics of our group of patients. 35 patients were included: 32 (91.4%) female and 3 (8.6%) male. The current median (min-max) age was 22 (16-35) years and the mean (SD) age at diagnosis was 15.8 (2.4) years. In regard to inflammatory activity in these patients, the median ESR was 19 (2- 75) mm/h and CRP was 1.65 (0.1-9.6) mg/L. The median serum albumin was 41.6 (16.7-46.3) g/L. The median proteinuria was 0.2 (0-3) g/dL, leukocyturia was 0 (0-1362.7)/uL, erythrocyturia was 0 (0-501.9)/uL and anti-double stranded DNA levels were 89.3 (10-800) U/mL. In relation to the complement components, the mean C3 values were 102.1 (21.6) and the C4 were 17.1 (7.4) mg/dL. The mean serum creatinine was 0.63 (0.1) mg/dL. The median of SLEDAI was 2 (0-12).Additionally, all patients were ANA positive, 40 % were positive for anti- nucleosome antibodies, 25.7% for anti-ribosomal P protein antibodies, 11.4% for anti-Sm antibodies, 37.1% for anti-SSA antibodies and 8.6%for anti-SSB antibodies. Relatively to the presence of antiphospholipid antibodies, 8.6% of patients were positive for antibodies against β2-glycoprotein I, 8.6% for anti-cardiolipin antibodies and 14.3% for lupus anticoagulant.
Musculoskeletal manifestations were present in 48.6% of patients, mucocutaneous in 77.1%, hematological in 45.7%, renal in 42.9%, serosal manifestations in 8.6% and pulmonary in 2.9%.
In relation to the lipid profile, the mean (SD) TC levels were 165.5 (44.7) mg/dL and LDL cholesterol were 94.5 (29.9) mg/dL. The median HDL levels were 52 (28-92) and TG were 81.5 (41-253) mg/dL.
Regarding the patients’ medication, the median daily prednisolone dose was 5 (0-40) mg. 88.6% of these patients were taking hydroxychloroquine, 31.4% mycophenolate mophetil and 14.3% azathioprine.
Total cholesterol was negatively correlated with serum albumin (p= 0.043, rho=-0.378) and positively with SLEDAI (p=0.032; rho= 0.392), proteinuria (p=0.009; rho= 0.469) and leukocyturia (p=0.031; rho= 0.394). A positive correlation was found between LDL cholesterol and proteinuria (p=0.043; rho= 0.385). Triglycerides were positively correlated with C-Reactive Protein (p=0.001; rho= 0.575) and prednisolone daily dose (p=0.035; rho= 0.394). HDL cholesterol correlated positively with proteinuria (p=0.026, rho= 0.407) and serum creatinine (p= 0.045, rho= 0.369) (Table II). Mean LDL cholesterol was higher in anti-Sm positive patients (p=0.022). No differences were found regarding anti-phospholipids antibodies (Table III).
Discussion
SLE is an independent risk factor for atherosclerosis and patients with juvenile-onset of the disease are at higher risk of developing cardiovascular diseases, such as myocardial infarction in adulthood7.
In this study TC and LDL cholesterol values were positively correlated with proteinuria. These results are in agreement with Sajjad et al14 and Liu et al15 who analyzed the lipid profile of adults with SLE and found a similar correlation with their proteinuria values. Additionally, this last study mentioned15 reported that TC was negatively correlated with serum albumin levels which is also similar to our results. We also found a positive correlation between TC and leukocyturia. In fact, during disease activity, the urinary sediment in SLE patients can present leukocyturia, hematuria, granular casts or hyaline casts. Hypoalbuminemia accompanied by significant proteinuria can also occur during active lupus renal disease16. Therefore, we conclude that lipid profile alterations in our group of patients is associated with an increase in disease activity that manifests through the increased proteinuria, leukocituria and hypoalbuminemia.
In this study we found a positive correlation between the patients’ TC and their SLEDAI. This result is supported by Yuan et al17 who evaluated 46 SLE patients and found that TC and TG serum levels correlated positively with the patients’ SLEDAI. In fact, other studies show that patients with SLE and dyslipidemia have higher SLEDAI compared to patients with SLE but without dyslipidemia18, 19. Also, Ardoin et al8 evaluated 221 children and adolescents with jSLE and found that a higher disease activity, measured through SLEDAI, was directly associated with higher LDL levels.
We also found a positive correlation between serum TG and CRP levels. In fact, a systematic review concluded that inflammatory mediators like CRP are proven to increase the TG levels5. Also, CRP levels are increased in patients with metabolic syndrome and in hypertriglyceridemia20. In reality, increased levels of CRP are an independent cardiovascular risk factor for myocardial infarction, peripheral artery disease and cardiac arrest8.
In our group of patients, HDL cholesterol correlated positively with the proteinuria and serum creatinine. That indicates that higher HDL cholesterol is
associated with higher disease activity, which is shown by worse renal function. This relationship is counterintuitive and previous studies14, 21 found a negative correlation between HDL cholesterol and proteinuria. In addition, Svenungson et al22 found that low levels of HDL were associated with active disease after studying the relationship between blood lipid levels and disease activity, clinical characteristics and inflammatory factors in 208 SLE patients.
HDL cholesterol is considered atheroprotective, because of its effect against LDL oxidation23, 24 and their role in reverse cholesterol transport from the atherosclerotic vessels back to the liver22. However, curiously, under chronic pro-inflammatory diseases like SLE, HDL can be oxidized and lead to higher LDL oxidation23, 24. In fact, the pro-inflammatory HDL form is associated with the progression of carotid plaques24. Our results may be in agreement with this argument, given a high level of HDL relates, in our sample, with kidney function worsening. We believe this relationship should be further explored in the future.
We also found that patients taking higher daily doses of prednisolone had higher TG levels. This result is in agreement with previous studies8, 22. In reality, corticosteroids usage in SLE treatment has a dual effect. Because atherogenesis is significantly influenced by the pro-inflammatory state of the disease, the anti-inflammatory action of corticosteroids would mean a decrease in cardiovascular risk. However, corticosteroids also enhance the rise of classic cardiovascular risk factors, such as dyslipidemia, hypertension, hyperglycemia and obesity24. This correlation can also be associated to the fact that patients taking higher daily doses of corticosteroids are usually patients with a more severe disease, more disease activity and, consequently, worse lipid profile. In fact, the chronic corticosteroid usage in SLE is associated to higher levels of TG, TC and its components LDL and HDL cholesterol5, 9. It is true that corticosteroids influence several alterations in the lipid metabolism, namely the increase in lipolysis, insulin resistance, lipoprotein lipase activity, adipokines activity and the inhibition of free fatty acid B-oxidation5, 20. The corticosteroids’ effect is dose dependent and low doses do not influence the lipid profile in a considerable manner5. In our cohort, mean LDL levels were higher in anti-Sm positive patients. Anti-Sm antibodies have a low sensitivity (10-55%), but a high specificity (98-100%) for SLE25.
Additionally, anti-Sm antibodies are associated with the presence of lupus nephritis25, 26. Thereby, it is possible to consider that there could be a relationship between higher LDL levels and renal lesion, since LDL levels were also positively associated with proteinuria.
Conclusion
In conclusion, in our group of patients with jSLE we found a relationship between the increased TC, TG and LDL levels and the disease activity. This activity is shown by renal manifestations (proteinuria, leukocyturia and hypoalbuminemia), by the increase in inflammatory markers (CRP) and by higher SLEDAI. In this sense, it is of high importance to monitor the jSLE patients’ lipid profile alterations. The management of the disease activity can help maintain a stable lipid metabolism and lower the risk for cardiovascular complications in these patients.References
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Table I. Clinical and demographic characteristics of the patients
Clinical and Demographic
characteristics N= 35
Women (%) 91.4
Age (min, max), years 22 (16, 35) Age at diagnosis ± SD, years 15.8 ± 2.4 ESR (min, max) (mm/h) 19 (2, 75) CRP (min, max) mg/L 1.65 (0.1, 9.6) Albumin (min, max) g/L 41.6 (16.7, 46.3) Proteinuria (min, max) g/dL 0.2 (0, 3) Leukocyturia (min, max) x/uL 0 (0, 1362.7) Erythrocyturia (min, max) x/uL 0 (0, 501.9) Anti-dsDNA antibodies (min, max)
U/mL
89.3 (10, 800) C3 ± SD mg/dL 102.1 ± 21.6
C4 ± SD mg/dL 17.1 ± 7.4
Creatinine ± SD mg/dL 0.63 ± 0.1 SLEDAI-2K (min, max) 2 (0, 12)
ANA (%) 100
Anti-nucleosome antibody (%) 40 Anti-ribosome P protein antibody (%) 25.7 Anti-Sm antibody (%) 11.4 Anti-SSA antibody (%) 37.1 Anti-SSB antibody (%) 8.6 Anti-β2-glycoprotein I antibody (%) 8.6 Anti-cardiolipin antibody (%) 8.6 Lupus anticoagulant (%) 14.3 Hematological manifestations (%) 45.7 Musculoskeletal manifestations (%) 48.6 Mucocutaneous manifestations (%) 77.1 Renal manifestations(%) 42.9 Serosal manifestations (%) 8.6 Pulmonary manifestations(%) 2.9 TC ± SD mg/dL 165.5 ± 44.7 LDL ± SD mg/dL 94.5 ± 29.9 HDL (min, max) mg/dL 52 (28, 92) TG (min, max) mg/dL 81.5 (41, 253) Prednisolone (%) 94
Prednisolone daily dose (min, max) mg
5 (0, 40) Hydroxychloroquine (%) 88.6 Mycophenolate Mophetil (%) 31.4
Azathioprine (%) 14.3
SD: Standard Deviation; ESR: Erythrocyte Sedimentation Rate; CRP: C-Reactive Protein; Anti-dsDNA: anti-double stranded DNA; C3: Complement component 3; C4: Complement component 4; SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index-2K; ANA: Antinuclear antibodies; TC: Total Cholesterol; LDL: Low Density Lipoprotein; HDL: High Density Lipoprotein; TG: Triglycerides.
Table II: Correlation between clinical values and lipid parameters Clinical values TC LDL TG HDL Pearson’s correlation coefficient p value Pearson’s correlation coefficient p value Spearman’s correlation coefficient p value Spearman’s correlation coefficient p value ESR (mm/h) 0.256 0.189 0.362 0.064 -0.055 0.779 -0.010 0.959 CRP mg/L -0.031 0.871 -0.117 0.560 0.575 0.001 -0.124 0.521 Albumin g/L -0.378 0.043 -0.186 0.353 -0.209 0.276 -0.259 0.175 Proteinuria g/dL 0.469 0.009 0.385 0.043 0.252 0.179 0.407 0.026 Leukocyturia x/uL 0.394 0.031 0.277 0.153 0.025 0.894 0.324 0.080 Erythrocyturia x/uL 0.241 0.199 0.092 0.642 0.256 0.172 -0.017 0.929 Anti-dsDNA antibodies U/mL 0.038 0.843 0.092 0.642 0.059 0.756 -0.187 0.321 C3 mg/dL -0.049 0.779 -0.090 0.648 0.233 0.237 -0.048 0.800 C4 mg/dL 0.123 0.526 0.028 0.890 -0.042 0.828 0.298 0.116 Creatinine mg/dL 0.060 0.754 0.033 0.868 -0.013 0.947 0.369 0.045 SLEDAI-2K 0.392 0.032 0.310 0.108 0.049 0.799 0.285 0.127 SLICC 0.261 0.164 0.289 0.136 -0.053 0.782 0.163 0.390 Prednisolone daily dose (mg) 0.290 0.127 0.211 0.291 0.394 0.035 0.342 0.069
ESR: Erythrocyte Sedimentation Rate; CRP: C-Reactive Protein; Anti-dsDNA: anti-double stranded DNA; C3: Complement component 3; C4: Complement component 4; SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index-2K; SLICC: Systemic Lupus International Collaboration Clinic; TC: Total Cholesterol; LDL: Low Density Lipoprotein; HDL: High Density Lipoprotein; TG: Triglycerides.
Table III: Correlation between clinical characteristics and lipid parameters TC LDL TG HDL Clinical Characteristics T-test p value T-test p value Mann-Whitney test p value Mann-Whitney test p value Anti-nucleosome antibody 0.212 0.324 0.352 0.176
Anti-ribosomal P protein antibody 0.597 0.851 0.396 0.787
Anti-Sm antibody 0.518 0.022 0.300 0.253 Anti-SSA antibody 0.203 0.078 0.698 0.948 Anti-SSB antibody 0.880 0.915 0.333 0.533 Anti-β2-glycoprotein I antibody 0.419 0.231 0.653 0.510 Anti-cardiolipin antibody 0.292 0.239 0.489 0.862 Lupus anticoagulant 0.084 0.114 0.512 0.851 Hematological manifestations 0.765 0.495 0.967 0.629 Musculoskeletal manifestations 0.312 0.917 0.419 0.294 Mucocutaneous manifestations 0.568 0.895 0.407 0.264 Renal manifestations 0.375 0.504 0.068 0.603 Serosal manifestations 0.734 0.581 0.557 0.268 Pulmonary manifestations 0.288 0.091 0.272 0.452 Prednisolone 0.242 0.156 0.126 0.659 Hydroxychloroquine 0.666 0.204 0.903 0.482 Mycophenolate Mophetil 0.456 0.368 0.132 0.354 Azathioprine 0.770 0.621 0.697 0.435
Agradecimentos
À Professora Doutora Iva Brito por me ter dado a oportunidade de ingressar neste projeto e por toda a sua disponibilidade e dedicação, indispensáveis ao sucesso da realização deste trabalho. À Doutora Sara Ganhão pelo apoio e ajuda incansáveis ao longo de todo o trabalho e pela prontidão e disponibilidade em responder às minhas dúvidas. Aos meus pais, irmãos e Ahmed pelo apoio incondicional e motivação para o sucesso.
ANEXO
Acta Reumatológica Portuguesa, Sociedade Portuguesa de Reumatologia
ACTA REUMATOLÓGICA PORTUGUESA
SPR – Sociedade Portuguesa de Reumatologia
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A Acta Reumatológica Portuguesa oferece aos autores um sistema de submissão e revisão de artigos a funcionar exclusivamente online. Acedendo ao website da ARP (www.actareumatologica.pt) os autores poderão submeter os seus artigos e acompanhar o seu estado no processo de revisão. Os autores serão notificados por email no próprio dia em que o(s) seu(s) artigo(s) sofra(m) alterações relevantes durante o processo editorial.
De modo a submeter um manuscrito, os autores deverão criar uma conta de utilizador:
- Aceder ao website da ARP (www.actareumatologica.pt), clicar no link “Entrar”, seguido de “Registo” e seguir cuidadosamente todas as instruções fornecidas. Um email de activação será enviado para a sua conta de email. Para activar a conta ARP é necessário seguir o link fornecido no corpo desse email, que automaticamente o redirecionará para uma mensagem de registo no website da ARP.
Após a criação de uma conta ARP, os autores poderão submeter e acompanhar o progresso
do(s) seu(s) artigo(s):
- Aceder ao website da ARP (www.actareumatologica.pt), entrar na area privada e clicar no link “Submeter artigo”. Preencher o formulário seguindo as instruções cuidadosamente.
Instruções aos autores
Para evitar atrasos no processo de revisão, leia cuidadosamente as instruções e assegure-se de que o seu manuscrito está de acordo com os requisitos da ARP antes de submeter (número de palavras e formato).
- Título do artigo: o título deve descrever brevemente o conteúdo do artigo. Não devem ser usadas abreviaturas. Deve ser indicado um curto título para rodapé. Nos artigos escritos em português é necessário incluir o título em inglês.
-Nome dos autores e afiliações
- Informações do autor responsável pela correspondência: nome, morada, telefone e endereço electrónico
- Resumo: com um máximo de 350 palavras ,deve incluir objectivos, material e métodos, resultados e conclusões. Para os casos clínicos o limite de palavras é 180.
Acta Reumatológica Portuguesa, Sociedade Portuguesa de Reumatologia Tipos de artigo:
- Editoriais: Os Editoriais serão solicitados por convite do Editor e constituirão comentários
sobre tópicos actuais ou sobre artigos publicados na revista. O texto dos Editoriais não deverá exceder as 1200 palavras, um máximo de 15 referências e pode conter uma figura ou tabela.
- Artigos de Revisão: Preferencialmente, os Artigos de Revisão serão também solicitados
pelo Editor. No entanto, os autores interessados em apresentar um Artigo de Revisão podem contactar o Editor para discussão dos temas a apresentar no artigo, o qual não deverá exceder as 4000 palavras, 6 Tabelas ou Figuras e 100 referências; a ARP aceitará preferencialmente revisões sistemáticas da literatura que cumpram com o PRISMA;
- Artigos Originais: O texto dos Artigos Originais deve ser apresentado com uma Introdução,
Material e Métodos, Resultados, Discussão e Conclusão. Não deverá exceder as 4000 palavras, 6 Tabelas ou Figuras e 60 referências. Assegurar que os estudos observacionais são apresentados de acordo com a declaração STOBE e que os ensaios aleatorizados de acordo com a CONSORT.
- Prática Clínica: O texto dos artigos de Prática Clínica deve ser apresentado com uma
Introdução, Material e Métodos, Resultados, Discussão e Conclusão. Não deverá exceder as 4000 palavras, 6 Tabelas ou Figuras e 60 referências;
- Revisões de Casos: A ARP aceitará, preferencialmente, Revisões de Casos. O texto deverá
ser apresentado com uma Introdução, Caso Clínico e Discussão, acompanhado de figuras ilustrativas/tabelas (máximo de 6). Não deverá exceder as 2000 palavras e 25 referências; - Imagens em Reumatologia: Imagens representando manifestações clínicas raras ou de
particular interesse podem ser submetidas (no máximo 4). O texto acompanhante não deverá exceder as 500 palavras e 5 referências
- Cartas ao Editor: As Cartas ao Editor deverão constituir um comentário critico a um artigo
da Revista ou uma pequena nota sobre um tema ou caso clinico. O texto não deverá exceder as 600 palavras, uma Figura/Tabela e um máximo de 10 referências.
Tabelas: As Tabelas a inserir devem ser assinaladas no texto em numeração romana. Cada
Tabela deverá possuir um título e não deverá apresentar linhas verticais. As linhas horizontais só deverão ser usadas como separadores de título e subtítulos. Todas as abreviaturas usadas devem ser explicadas na parte inferior da Tabela.
Figuras: As Figuras a inserir devem ser assinaladas no texto em numeração árabe e apresentar
legendas. Cada Figura deve ser importada individualmente em format JPEG ou TIFF de alta qualidade. O Editor reserva o direito de agrupar Figuras ou alterar o seu tamanho de modo a rentabilizar o uso da páginas.
Referências: As Referências bibliográficas devem ser classificadas e numeradas por ordem de
entrada no texto e em superscript. As abreviaturas usadas na nomeação das revistas devem ser as utilizadas pelo Index Medicus. Nas Referências com 6 ou menos autores, todos devem ser nomeados. Nas Referências com 7 ou mais autores, devem ser nomeados os 3 primeiros seguidos de et al. Os números de página inicial e final devem ser totalmente apresentados (ex. 565-569 e não 565-9). Não indicar o número da Revista nem o mês da publicação. As
Acta Reumatológica Portuguesa, Sociedade Portuguesa de Reumatologia
Referências correspondentes a trabalhos não publicados, apresentações ou observações pessoais, devem ser inseridas no próprio texto (em parenthesis) e não como Referências convencionais. Os autores são responsáveis pela exactidão das Referências apresentadas. Seguem-se alguns exemplos de como devem constar os vários tipos de Referências:
Revista
Nome(s) e iniciais do(s) autor(es). Título do artigo. Nome da Revista Ano; Volume: Página (s).
Ex: Hill J, Bird HA, Hopkins R, Lawton C, Wright C. Survey of satisfaction with care in a rheumatology outpatient clinic. Ann Rheum Dis 1992; 51: 195-197.
Artigo publicado online (inserir DOI)
Nome(s) e iniciais do(s) autor(es). Título do artigo. Nome da Revista Published Online First: data. doi.
Ex: Merkel PA, Curthbertson D, Hellmich B et al. Comparison of disease activity measures for ANCA-associated vasculitis. Ann Rheum Dis Published Online First: 29 July 2008. doi:10.1136/ard.2008.097758.
Capítulo de livro
Nome(s) e iniciais do(s) autor(es) do capítulo. Título do capítulo. In: Nome(s) e iniciais do(s) editor(es) medico(s). Título do livro. Cidade: Nome da casa editorial, ano de publicação: primeira a última página do capítulo.
Ex: Stewart AF. Hypercalcemia resulting from medications. In: Favus MD, ed Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. New York: Raven Press, 1991: 177-178.
Livro
Nome(s) e iniciais do(s) autor(es). Título do livro. Cidade: Nome da casa editorial, ano de publicação: página(s).
Ex: Lorig K. Patient Education. A practical approach. St Louis: Mosby-Year Book, 1992: 51.
Documento electrónico
Título do documento. http://address. Data de acesso.
Ex: Programa Nacional de Luta Contra a Tuberculose. Sistema de Vigilância (SVIG-TB). Direcção-Geral da Saúde – Divisão de Doenças Transmissíveis, Março de 2005. http://www.dgsaude.pt/upload/membro.id/ficheiros/i006875.pdf. Accessed in January 25th 2008.
Agradecimentos
Incluir nesta secção agradecimentos a pessoas que tenham contribuído para o trabalho mas sem autoria. Instituições ou fontes de apoio financeiro também poderão aqui ser indicadas.
Acta Reumatológica Portuguesa, Sociedade Portuguesa de Reumatologia
Os artigos submetidos são enviados a revisores especializados no tema do artigo. Concluída a revisão do artigo, os autores são notificados, recebendo os pareceres e comentários dos revisores acerca do estado do mesmo. Com base nesses pareceres, os autores deverão editar o artigo, corrigi-lo e resubmetê-lo para nova revisão. Na resubmissão de um artigo terão de ser incluídas em anexo uma carta-resposta aos Revisores e um .doc com uma versão do artigo em track changes. Este documento não deverá ter qualquer identificação dos autores nem as respectivas afiliações. Caso o artigo se mantenha sem uma resposta dos autores durante mais de 6 meses, a Equipa editorial reserva-se no direito de o retirar do processo de revisão.
Critérios de Revisão
Os critérios de aceitação de um artigo para publicação têm em consideração a qualidade e originalidade do artigo apresentado, a excelência na redacção e organização do mesmo e o potencial impacto na literatura médica.
Todos os artigos aceites para publicação serão mantidos e apresentados como “online-first” até que os Editores os seleccionem para integrar um número específico da Revista.
Revisão de provas
Os autores dos artigos aceites para publicação receberão uma versão digital da prova do artigo para valiação. Assim, as provas devem ser revistas durante as 72h que sucedem a sua recepção. Os autores são responsáveis pela cuidada revisão do texto, Figuras, Tabelas, Legendas e Referências, e deverão contactar os Editores no caso em que sejam necessárias alterações. Apenas pequenas alterações e correcções tipográficas são permitidas nesta fase.
Direitos de autor
Após aceitação para publicação, os autores transferem para a ARP os direitos de autor do manuscrito.
