Expert's corner: a personal approach
How I diagnose and treat lupus
D.Á. Galarza-Delgado
, A.C. Arana-Guajardo
Corresponding author
dgalarza@medicinauanl.mx
Corresponding author at: Servicio de Reumatología del Departamento de Medicina Interna del Hospital Universitario, “Dr. José Eleuterio González”, de la UANL, Av. Madero y Av. Gonzalitos s/n, col. Mitras Centro, CP 64460 Monterrey, NL, Mexico. Tel.: +52 81 8333 7798.
Corresponding author at: Servicio de Reumatología del Departamento de Medicina Interna del Hospital Universitario, “Dr. José Eleuterio González”, de la UANL, Av. Madero y Av. Gonzalitos s/n, col. Mitras Centro, CP 64460 Monterrey, NL, Mexico. Tel.: +52 81 8333 7798.
Servicio de Reumatología, Departamento de Medicina Interna del Hospital Universitario, “Dr. José Eleuterio González”, de la Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico
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Capetillo-Ventura, S.I. Jalil-Pérez, K. Motilla-Negrete" "autores" => array:3 [ 0 => array:2 [ "nombre" => "N.C." "apellidos" => "Capetillo-Ventura" ] 1 => array:2 [ "nombre" => "S.I." "apellidos" => "Jalil-Pérez" ] 2 => array:2 [ "nombre" => "K." "apellidos" => "Motilla-Negrete" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665579615000071?idApp=UINPBA00004N" "url" => "/16655796/0000001700000066/v1_201508210029/S1665579615000071/v1_201508210029/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Expert's corner: a personal approach</span>" "titulo" => "How I diagnose and treat lupus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "59" "paginaFinal" => "63" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D.Á. Galarza-Delgado, A.C. Arana-Guajardo" "autores" => array:2 [ 0 => array:4 [ "nombre" => "D.Á." "apellidos" => "Galarza-Delgado" "email" => array:1 [ 0 => "dgalarza@medicinauanl.mx" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.C." "apellidos" => "Arana-Guajardo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Reumatología, Departamento de Medicina Interna del Hospital Universitario, “Dr. José Eleuterio González”, de la Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Servicio de Reumatología del Departamento de Medicina Interna del Hospital Universitario, “Dr. José Eleuterio González”, de la UANL, Av. Madero y Av. Gonzalitos s/n, col. Mitras Centro, CP 64460 Monterrey, NL, Mexico. Tel.: +52 81 8333 7798." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1607 "Ancho" => 1634 "Tamanyo" => 230207 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Stepwise approach in the treatment of SLE. NSAID, Nonsteroidal antiinflammatory drugs; IVIg, intravenous immunoglobulin; SLE, systemic lupus erythematosus.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease of unknown origin with a waxing and waning course and a significant morbi-mortality. The objective of this paper is to provide an SLE overview, as well as recommendations regarding diagnosis and therapeutic concepts. In the first stage of the disease, the combination of genetic, gender and environmental factors culminate in the formation of autoantibodies years before the onset of symptoms is observed. In the second phase, there are clinical manifestations and associations with comorbidities. Management of patients with SLE should be predictive, preventive, personalized, and participatory in order to achieve remission and prevent relapses. We can divide SLE into three categories according to the severity of the disease: mild, moderate, and severe. Corticosteroids are the mainstay of therapy, but the use of another agent is mandatory in order to reduce side effects. Some of the biological agents used in immunosuppressive therapy in SLE treatment include methotrexate, antimalarials, azathioprine, mycophenolate mofetil, cyclophosphamide, belimumab and rituximab.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="par0010" class="elsevierStylePara elsevierViewall">Diagnosing Systemic Lupus Erythematosus (SLE) has been a challenge over the years. The first reports of the disease only considered skin manifestations. Later, William Osler recognized the systemic involvement of the disease.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">1</span></a> SLE is a multisystemic autoimmune disease of unknown origin.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a> SLE has an incidence of 1–10 per 100,000 person-years and a prevalence of 20–70 per 100,000 inhabitants.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> SLE prevalence in Hispanics is 138.7–244.5 per 100,000 people.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">4</span></a> For every 9–10 women with SLE, 1 male will be affected.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a> SLE has a waxing and waning course with significant morbidity that can be fatal – if not treated early – in some patients. A diagnosis of SLE should be considered when a patient has characteristic features of SLE associated with autoantibody formation<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">5</span></a>; thus, the presence of anti-nuclear antibodies (ANA) is considered necessary for an SLE diagnosis. Patients without ANA will have less than a 3% probability of developing the disease.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objectives of this paper are to provide an overview based on the literature and on the personal experience of 30 years of treating patients with SLE, provide general and specific recommendations regarding the diagnosis of this challenging disease, and share therapeutic concepts that are fundamental for the comprehensive management of the disease.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">SLE stages</span><p id="par0020" class="elsevierStylePara elsevierViewall">SLE stages include a preclinical and a clinical phase, as well as its related comorbidities.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Clinical manifestations only develop in predisposed individuals and are secondary to a loss of tolerance with a subsequent immune dysregulation<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The development of autoimmunity is determined by genetic, gender, and environmental factors. Advances in genetic techniques have identified more than 30 genetic associations with SLE including variants of HLA and Fcγ receptor genes, IRF5, STAT4, PTPN22, TNFAIP3, BLK, BANK1, TNFSF4 and ITGAM.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">7</span></a> Moreover, the genetic contribution to the development of SLE has been observed in twins, with a concordance between monozygotic twins of 24–56% vs 2–5% in dizygotic twins.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">8</span></a> Female preponderance in the pathogenesis of SLE has been demonstrated in transgenic mice. Smith-Bouvier et al. observed that mice with the XX chromosome were more susceptible to developing lupus when compared to XY mice.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">9</span></a> Environmental factors can contribute to the development of SLE by the inhibition of DNA methylation.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">10</span></a> These factors include drugs (e.g. procainamide), diet, smoking, UV light exposure and infections (Epstein–Barr virus).<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">11</span></a> Finally, there is a pathogenic autoantibody production in SLE patients, reflecting loss of tolerance.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Different authors have described the development of autoantibodies before the clinical onset of the disease in the past. Arbuckle et al. described the presence of at least one SLE autoantibody before the diagnosis (up to 9.4 years earlier; mean, 3.3 years) in asymptomatic patients. Antinuclear, antiphospholipid, anti-Ro and anti-La antibodies preceded the other autoantibodies in this cohort of patients.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">12</span></a> Subsequently, McClain et al. described the clinical significance of the presence of antiphospholipid antibodies prior to an SLE diagnosis, as well as the presence of these autoantibodies in patients with a more severe clinical outcome.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In order to classify patients in the early stages of the disease, different authors have proposed definitions according to the symptoms and the presence of classification criteria. First, the term undifferentiated connective tissue disease (UCTD) is used in individuals with a disease manifestation suggestive but not diagnostic of a specific connective tissue disease. UCTD accounts for 10–20% of referred patients, 10–15% will fulfill the classification criteria for SLE 5 years later.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a> Factors that predict evolution to SLE are young age, alopecia, serositis, discoid lupus, a positive anti-human globulin (Coombs) test and anti-Sm or anti-DNA antibodies.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Ganczarczyk et al. described the term “latent lupus” to define patients with features consistent with SLE which may or may not be a part of the American College of Rheumatology (ACR) classification criteria, but still are ≤4.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Incomplete lupus refers to patients with less than four ACR classification criteria for SLE. Swaak et al. in a multicentric study, observed that only three of 122 incomplete lupus patients developed SLE during 3 years of follow-up, and suggested that incomplete SLE forms a subgroup with a good prognosis.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a> Later, Greer et al. confirmed this observation. They followed 38 incomplete lupus patients over 19 months and only two developed SLE.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">18</span></a> An additional term is preclinical lupus, which defines individuals with increased genetic risk for the development of SLE but no clinical symptoms.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">After the preclinical stage, the clinical stage occurs with the onset of symptoms. The GLADEL (Grupo Latinoamericano de Estudio de Lupus) cohort, a multinational inception prospective cohort in Latin American centers, described the symptoms in 1214 patients with SLE. They found that arthralgia and/or arthritis, fever, photosensitivity, alopecia and malar rash were the most common symptoms at onset.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">SLE treatment</span><p id="par0055" class="elsevierStylePara elsevierViewall">SLE management represents the “P4”, a new paradigm of modern medicine. P4 Medicine stands for Predictive, Preventive, Personalized and Participatory Medicine.</p><p id="par0060" class="elsevierStylePara elsevierViewall">SLE is a syndrome with high variability in the disease course as well as in the severity of the manifestations; therefore each SLE patient should be treated on an individualized basis in order to implement a proper treatment.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a> The goal of the treatment is to achieve remission, prevent flares and use of drugs with the minimum dose required to prevent long-term side effects. The treatment includes lifestyle modification, patient education, physical activity and medical or (in some cases) surgical intervention.</p><p id="par0065" class="elsevierStylePara elsevierViewall">There are general recommendations that are given to SLE patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). All patients should have a balanced diet and exercise regularly. Patients are advised to avoid Echinacea, melatonin, garlic, and alfalfa sprouts, which have been described to precipitate their condition.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">22</span></a> It is also important to inform patients to avoid disease reactivation drugs such as procainamide, hydralazine, sulfonamides, anti-TNFa, ibuprofen or estrogen.<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">23,24</span></a> Smoking also appears to influence the onset and course of the disease among patients with SLE.<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">25,26</span></a> The effect of drugs like methotrexate (MTX) and hydroxychloroquine (HCQ) may diminish with smoking.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The vaccination schedule in SLE patients includes a yearly influenza vaccine and a pneumococcal vaccine every 5 years. Hepatitis B and Tetanus toxoid vaccinations also seem to be safe, and not associated with flares.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a> The quadrivalent human papillomavirus vaccine is also safe and not associated with increased lupus activity.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">28</span></a> It is important to consider that inactivated live vaccines are contraindicated in patients taking immunosuppressive drugs and/or glucocorticoids at a dose >20<span class="elsevierStyleHsp" style=""></span>mg/day.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">27</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Most SLE patients are diagnosed in the reproductive years, thus reproductive health is an important issue. It is recommended for SLE patients to have an inactive disease for a six month period prior to conception. There are three main types of contraceptives: barrier methods, intrauterine devices and the hormonal method. Hormonal methods include combined or progestin-only. The use of combined methods is associated with an increased risk of SLE,<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a> however, progesterone methods have proven to be safe for SLE patients.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In addition to the control of the disease, SLE patients should have a systematic assessment of comorbidities. SLE patients develop premature atherosclerosis and their risk of heart attack and stroke is 10 times higher than that of age-matched controls.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">31</span></a> Atherosclerosis is the result of the complex interplay between dysfunctional immune regulation, inflammation, traditional risk factors, aberrant endothelial cell function and repair, and the therapeutics for treating the underlying autoimmune disease.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a> SLE patients also have an increased risk of different types of cancer such as non-Hodgkin lymphoma, lung cancer, and cervical dysplasia. Lupus disease activity, smoking and immunosuppressive drug exposure are some of the causes of the increase in cancer risk.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Therefore, SLE patients should have colonoscopies, Pap smear, and mammogram schedules.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Cognitive dysfunction prevalence in SLE ranges from 12% to 87%. Petri et al. compared cognitive functioning in recently diagnosed SLE patients versus normal controls. Using Automated Neuropsychological Assessment Metrics (ANAM), SLE patients performed significantly worse than normal controls. Therefore, a cognitive assessment is necessary in all SLE patients from the onset of the disease.</p><p id="par0090" class="elsevierStylePara elsevierViewall">We can divide SLE into three categories based on disease severity: mild, moderate, and severe (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Corticosteroids (CS) are the mainstay of treatment for SLE in any category, with proven efficacy.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a> The dose varies according to the severity of symptoms. A low dose is 0.1–0.2<span class="elsevierStyleHsp" style=""></span>mg/kg/day, an intermediate dose is 0.3–0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day, and a high dose is 0.6–2<span class="elsevierStyleHsp" style=""></span>mg/kg/day. The use of this drug is associated with an increase in serum lipids, blood pressure, weight and glucose, in addition to cataracts and osteoporotic fractures. The adverse side effects of CS depend on both the current and the cumulative dosage. Thamer et al. demonstrated the hazard ratio for accrued organ damage to be 1.5, 1.64 and 2.51 with prednisone doses of 6<span class="elsevierStyleHsp" style=""></span>mg/day, 12<span class="elsevierStyleHsp" style=""></span>mg/day and >18<span class="elsevierStyleHsp" style=""></span>mg/day, respectively.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> It is important to note that SLE diagnosis is not equivalent to the use of methylprednisolone, and that in many cases the deleterious effects of CS may outweigh the benefits. Therefore, the goal is the use of CS according to the clinical manifestations and slow tapering to 1–2<span class="elsevierStyleHsp" style=""></span>mg/day. In order to reduce CS doses and side effects, the use of another agent is mandatory.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Mild SLE includes mucocutaneous lesions, arthralgias and fatigue. Sun protection consists of avoiding when the sun is at its highest (10<span class="elsevierStyleHsp" style=""></span>am to 4<span class="elsevierStyleHsp" style=""></span>pm) and patients should use agents with a sun protection factor of at least 50, applied 20–30<span class="elsevierStyleHsp" style=""></span>min prior to exposure, and reapplied every 4<span class="elsevierStyleHsp" style=""></span>h. Topical therapies depend on whether it is a localized or widespread skin disease. Therapies include steroids and/or calcineurin inhibitors.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a> Systemic therapies include antimalarial agents, MTX, azathioprine, mycophenolate mofetil (MMF), dapsone, and cyclophosphamide (CYC), and are used in refractory diseases or in poor responses to treatment.<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">34,36</span></a> For cutaneovascular manifestations (Raynaud syndrome, livedo reticularis, etc.) the use of cold-preventive measures and calcium channel blockers can be beneficial. Nonsteroidal antiinflammatory drugs (NSAID) can be used in headaches, myalgias, arthralgias, and serositis. NSAID use must be monitored; side effects could be renal, gastrointestinal or cardiovascular. In my experience, I have seen severe secondary side effects such as aseptic meningitis. Ibuprofen is the drug most frequently involved in aseptic meningitis, but sulindac and naproxen have also been described.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">37</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Moderate SLE includes arthritis, serositis, and crops of mouth ulcers. Arthritis can improve with NSAID, moderate doses of prednisone, or antimalarial drugs. When the response is poor, MTX, leflunomide, azathioprine and TNF-a agents can be used.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">38</span></a> Serositis (pleurisy, pericarditis) responds to NSAID and CS. Belimumab is a fully humanized IgG1 mAb that binds to soluble BLyS (B lymphocyte stimulator), inhibiting its activity.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a> BLISS-52 and BLISS 76 demonstrated significant clinical responses with Belimumab compared to placebos in patients with mild and moderate disease activity (without nephritis/CNS).<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">39,40</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The severe SLE stage includes hemolytic anemia, thrombocytopenia, diffuse alveolar hemorrhage, necrotizing vasculitis, neuropsychiatric lupus and renal involvement. In this stage, CS is used in high doses and intravenous methylprednisolone pulses for severe cases. In hemolytic anemia and thrombocytopenia the treatment includes CS and danazol, Rituximab, intravenous immunoglobulin (IVIg), MMF, CYC, plasmapheresis and/or splenectomy for refractory cases.<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">41</span></a> The use of CYC and high doses of CS are also employed for diffuse alveolar hemorrhage, and plasmapheresis for refractory cases. We made an observational, retrospective study that included twelve SLE patients with alveolar hemorrhage. We found that simultaneous treatment with CS, CYC, plasmapheresis and IVIg was associated with a mortality of 17%, contrary to the rate previously described of up to 70–90%.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">42</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">According to the recommendations, glucocorticoid and immunosuppressive therapy is indicated for severe neuropsychiatric manifestations (myelopathy, optic neuritis, etc.). Anticoagulation therapy is indicated for the SNC manifestations of antiphospholipid syndrome.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">43</span></a> In our practice, we have also observed that the combination of methylprednisolone, CYC, IVIg and Rituximab was effective for psychosis refractory to conventional treatment.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Renal involvement is considered the most important prognostic factor. The Task Force Panel for screening, treatment, and management of Lupus Nephritis (LN) recommended the treatment to be based on the type of LN according to the ISN/RPS criteria.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">44</span></a> The treatment consists of the use of corticosteroids either solely or in combination with immunosuppressive agents. The recommendations for LN treatment include an induction and a maintaining therapy. There are 2 regimens for Class III/IV LN, low-dose “Euro-Lupus” CYC and high-dose CYC followed by maintenance treatment with MMF or azathioprine.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">45</span></a> In our practice, we believe that a low-dose CYC is more beneficial to patients decreasing adverse effects, such as infections, gonadal toxicity and increased risk of cancer. We do not share the idea that methylprednisolone pulses will provide a greater benefit than prednisone. And finally, LN response should be evaluated 3–6 months after initiating treatment.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, SLE is a challenging disease to diagnose and treat. Advances in research have allowed us to know which individuals are at risk of developing the disease. Each patient should be treated on an individualized basis according to their clinical manifestations in order to provide proper treatment.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Funding</span><p id="par0130" class="elsevierStylePara elsevierViewall">No financial support was provided.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Background" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "SLE stages" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "SLE treatment" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-10-15" "fechaAceptado" => "2014-11-04" "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1143 "Ancho" => 1642 "Tamanyo" => 90627 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Proposed current stages for developing clinical manifestations of Systemic Lupus Erythematosus.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1607 "Ancho" => 1634 "Tamanyo" => 230207 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Stepwise approach in the treatment of SLE. NSAID, Nonsteroidal antiinflammatory drugs; IVIg, intravenous immunoglobulin; SLE, systemic lupus erythematosus.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Balanced diet and exercise \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Avoid substances and drugs that might induce lupus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">No smoking \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vaccination schedule \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Assessment of cardiovascular risk factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Screening of cancer \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Evaluation of reproductive health \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Assessment of cognitive function \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab871766.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Systemic lupus erythematosus.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">General recommendations for SLE<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0230" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dubois lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 133 | 8 | 141 |
| 2024 September | 226 | 4 | 230 |
| 2024 August | 208 | 6 | 214 |
| 2024 July | 265 | 13 | 278 |
| 2024 June | 180 | 14 | 194 |
| 2024 May | 250 | 17 | 267 |
| 2024 April | 249 | 38 | 287 |
| 2024 March | 244 | 10 | 254 |
| 2024 February | 252 | 32 | 284 |
| 2024 January | 276 | 19 | 295 |
| 2023 December | 225 | 38 | 263 |
| 2023 November | 240 | 20 | 260 |
| 2023 October | 246 | 25 | 271 |
| 2023 September | 203 | 12 | 215 |
| 2023 August | 152 | 9 | 161 |
| 2023 July | 129 | 11 | 140 |
| 2023 June | 137 | 24 | 161 |
| 2023 May | 234 | 25 | 259 |
| 2023 April | 246 | 16 | 262 |
| 2023 March | 274 | 19 | 293 |
| 2023 February | 167 | 12 | 179 |
| 2023 January | 163 | 13 | 176 |
| 2022 December | 157 | 16 | 173 |
| 2022 November | 206 | 40 | 246 |
| 2022 October | 177 | 13 | 190 |
| 2022 September | 175 | 24 | 199 |
| 2022 August | 170 | 37 | 207 |
| 2022 July | 139 | 17 | 156 |
| 2022 June | 179 | 17 | 196 |
| 2022 May | 176 | 25 | 201 |
| 2022 April | 301 | 16 | 317 |
| 2022 March | 412 | 41 | 453 |
| 2022 February | 366 | 17 | 383 |
| 2022 January | 191 | 36 | 227 |
| 2021 December | 154 | 16 | 170 |
| 2021 November | 126 | 21 | 147 |
| 2021 October | 192 | 21 | 213 |
| 2021 September | 136 | 21 | 157 |
| 2021 August | 147 | 14 | 161 |
| 2021 July | 98 | 7 | 105 |
| 2021 June | 100 | 6 | 106 |
| 2021 May | 107 | 10 | 117 |
| 2021 April | 527 | 46 | 573 |
| 2021 March | 348 | 14 | 362 |
| 2021 February | 229 | 30 | 259 |
| 2021 January | 216 | 22 | 238 |
| 2020 December | 225 | 19 | 244 |
| 2020 November | 254 | 30 | 284 |
| 2020 October | 154 | 24 | 178 |
| 2020 September | 165 | 17 | 182 |
| 2020 August | 151 | 14 | 165 |
| 2020 July | 151 | 19 | 170 |
| 2020 June | 124 | 23 | 147 |
| 2020 May | 122 | 16 | 138 |
| 2020 April | 117 | 14 | 131 |
| 2020 March | 178 | 12 | 190 |
| 2020 February | 96 | 6 | 102 |
| 2020 January | 83 | 8 | 91 |
| 2019 December | 54 | 15 | 69 |
| 2019 November | 47 | 9 | 56 |
| 2019 October | 80 | 14 | 94 |
| 2019 September | 78 | 5 | 83 |
| 2019 August | 61 | 8 | 69 |
| 2019 July | 72 | 11 | 83 |
| 2019 June | 109 | 30 | 139 |
| 2019 May | 230 | 42 | 272 |
| 2019 April | 285 | 26 | 311 |
| 2019 March | 226 | 14 | 240 |
| 2019 February | 224 | 12 | 236 |
| 2019 January | 206 | 12 | 218 |
| 2018 December | 182 | 5 | 187 |
| 2018 November | 280 | 13 | 293 |
| 2018 October | 166 | 7 | 173 |
| 2018 September | 206 | 9 | 215 |
| 2018 August | 148 | 8 | 156 |
| 2018 July | 110 | 2 | 112 |
| 2018 June | 68 | 2 | 70 |
| 2018 May | 81 | 4 | 85 |
| 2018 April | 69 | 7 | 76 |
| 2018 March | 69 | 2 | 71 |
| 2018 February | 54 | 2 | 56 |
| 2018 January | 40 | 3 | 43 |
| 2017 December | 42 | 2 | 44 |
| 2017 November | 44 | 5 | 49 |
| 2017 October | 24 | 3 | 27 |
| 2017 September | 21 | 4 | 25 |
| 2017 August | 50 | 4 | 54 |
| 2017 July | 46 | 1 | 47 |
| 2017 June | 31 | 16 | 47 |
| 2017 May | 51 | 4 | 55 |
| 2017 April | 35 | 18 | 53 |
| 2017 March | 51 | 35 | 86 |
| 2017 February | 139 | 5 | 144 |
| 2017 January | 33 | 4 | 37 |
| 2016 December | 52 | 3 | 55 |
| 2016 November | 51 | 4 | 55 |
| 2016 October | 85 | 6 | 91 |
| 2016 September | 98 | 9 | 107 |
| 2016 August | 50 | 12 | 62 |
| 2016 July | 43 | 1 | 44 |
| 2016 June | 54 | 12 | 66 |
| 2016 May | 40 | 17 | 57 |
| 2016 April | 43 | 28 | 71 |
| 2016 March | 59 | 19 | 78 |
| 2016 February | 41 | 17 | 58 |
| 2016 January | 32 | 17 | 49 |
| 2015 December | 45 | 15 | 60 |
| 2015 November | 40 | 19 | 59 |
| 2015 October | 39 | 19 | 58 |
| 2015 September | 20 | 5 | 25 |
| 2015 August | 6 | 2 | 8 |
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