Tuberculosis in Patients With Systemic Lupus Erythematosus: Spain's Situation

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Note that the maternal haplotype called (b) share the Class II alleles (DRB1*0407-DQB1*03) with the paternal haplotype called (d). This paternal haplotype is present in all patients with SLE." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alicia Habegger de Sorrentino, Marcela Young, Karina Marinic, Patricia Fabiana Motta, Carlos Baruzzo" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Alicia" "apellidos" => "Habegger de Sorrentino" ] 1 => array:2 [ "nombre" => "Marcela" "apellidos" => "Young" ] 2 => array:2 [ "nombre" => "Karina" "apellidos" => "Marinic" ] 3 => array:2 [ "nombre" => "Patricia Fabiana" "apellidos" => "Motta" ] 4 => array:2 [ "nombre" => "Carlos" "apellidos" => "Baruzzo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1699258X13000235" "doi" => "10.1016/j.reuma.2012.11.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X13000235?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574313000543?idApp=UINPBA00004M" "url" => "/21735743/0000000900000006/v1_201311210124/S2173574313000543/v1_201311210124/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Tuberculosis in Patients With Systemic Lupus Erythematosus: Spain's Situation" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "369" "paginaFinal" => "372" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María del Mar Arenas Miras, Carmen Hidalgo Tenorio, Juan Jimenez Alonso" "autores" => array:3 [ 0 => array:4 [ "nombre" => "María del Mar" "apellidos" => "Arenas Miras" "email" => array:1 [ 0 => "mmararenas@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Hidalgo Tenorio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Juan" "apellidos" => "Jimenez Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección de Infecciosas, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La infección tuberculosa en pacientes con lupus eritematoso sistémico: situación en España" ] ] "textoCompleto" => "Tuberculosis is the most common infectious disease in the world, estimated at about 8 million new cases per year, with 12 million existing cases, involving a total of 20 million cases annually.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Consequently, the general population is more exposed to the TB bacilli, something particularly disturbing in immunocompromised persons, including patients with systemic lupus erythematosus (SLE),<a class="elsevierStyleCrossRef" href="#bib0010">2</a> and this phenomenon is exacerbated in developing countries that have detected a high incidence of extrapulmonary tuberculosis with high mortality<a class="elsevierStyleCrossRef" href="#bib0015">3</a> figures.In Spain the actual incidence of tuberculosis in the general population is not well known due to, among other causes, underreporting and underdiagnosis, especially among the elderly population.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> In recent years there has been a decline in the number of reported cases, reaching 5795 in 2007, although it is estimated that approximately 30%–40% of cases are not reported, so the numbers could be significantly higher.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> According to data from the National Epidemiological Surveillance Network, the total number of cases reported in 2009 was 7652, equivalent to a crude incidence rate of 16.96 cases per 100000 persons. Communities with higher overall rates were Ceuta, Galicia, La Rioja and Melilla, although the number of reported cases include Catalonia, Andalusia, and Madrid.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Currently, the main causes of death in patients with lupus are cardiovascular<a class="elsevierStyleCrossRef" href="#bib0035">7</a> disorders and infections, the latter predominating in several series.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> The administration of steroids and cyclophosphamide are 2 of the main risk factors in the development of infection.<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> Differential diagnosis between infection and lupus flares is sometimes difficult, but essential because delays in treatment of both processes are associated with increased mortality.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Moreover, TB simulates some of the findings of autoimmune diseases such as joint pain/arthritis, rash or presence of autoantibodies, which poses a problem for the diagnosis of this disease.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>In patients with SLE there are immunologic and genetic alterations that predispose them to the development of infections.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Among those described are a deficit in complement, functional asplenia, impaired phagocytic system or functional deficits in the activity of T cells, with reduced cytotoxic T cells and alterations in the function of suppressor T cells, determining increased susceptibility to infections by mycobacteria.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Added to this, the use of immunosuppressive agents such as azathioprine, cyclophosphamide or mycophenolate produces decreased T and B lymphocytes counts, and the widespread use of corticosteroids blocks T cell proliferation, cytotoxic T cells, microbicidal activity and antigen-specific immune response, producing a significant impairment of cellular immunity, and increased risk of infection by intracellular pathogens such as Mycobacterium tuberculosis, viruses of the herpes family and Pneumocystis jirovecii among other pathogens such as Listeria spp. and Nocardia spp.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>In countries where TB is endemic there have been numerous studies in patients with lupus. However, in Spain these are scarce and inconclusive.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4,16</a>In a retrospective study comprising 390 patients with SLE from the Philippines,<a class="elsevierStyleCrossRef" href="#bib0060">12</a> 13.8% had active tuberculosis, and of these, 74% had only pulmonary involvement; it also found that patients with disseminated infection had a higher lupus activity index and more aggressive disease, regardless of the corticosteroid dose they were receiving at the time of diagnosis. In another retrospective<a class="elsevierStyleCrossRef" href="#bib0085">17</a> study that included 283 SLE patients and 284 with rheumatoid arthritis from Korea, it was found that the most common form of involvement was pulmonary tuberculosis and lupus, mainly in patients with higher doses of corticosteroids. Alongside this, a greater percentage of extrapulmonary tuberculosis was described in lupus patients than in the general population, up to 45% of cases by one of the published series,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> and the main risk factor was higher daily or cumulative doses of corticosteroids during the year before diagnosis, more often for arthritis and renal involvement. These findings were similar to those described by Tam et al.,<a class="elsevierStyleCrossRef" href="#bib0095">19</a> who conducted a case-control study in Hong Kong consisting of 526 patients with SLE an who provided analysis of the different risk factors involved in the development of active tuberculosis. In this study, a univariate analysis, patients with SLE and cerebral involvement had higher rates of tuberculosis, nephritis, vasculitis, cumulative dose of corticosteroids and intravenous methylprednisolone pulses relative to the control group. In the multivariate analysis, the presence of nephritis and the cumulative dose of corticosteroids were independent risk factors for developing the disease. They also found an increase of extrapulmonary tuberculosis, which together with the military for, was the most common presentation in patients (67%). The other risk factor independently associated with the occurrence of tuberculosis in patients with SLE was pleuritis.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>As for Spanish studies on tuberculosis in patients with lupus, there have been three types so far. The first was a retrospective study which consisted of patients with lupus treated in the Systemic Autoimmune Diseases Unit of the Hospital de Cruces in the Basque Country between 1994 and 2003.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> In this, the incidence of active tuberculosis in patients with SLE (187 cases per 100000) was compared with the population of the area (20–45 cases per 100000), which turned out to be much lower than that of patients with lupus, and no predictor for the development of tuberculosis was identified among their patients. The second, also retrospective, was held at the Rheumatology Service, Hospital Clinico San Carlos in Madrid, and was composed of patients diagnosed with autoimmune disease and tuberculosis treated at the Unit.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> They found an incidence rate of tuberculosis in patients with autoimmune diseases of 153 cases per 100000 patient-years, which increased to 645 cases/100000 patient years when analyzing patients with SLE and vasculitis; in that year the incidence of tuberculosis in the Autonomous Community of Madrid was 26 cases per 100000 population per year, concluding that extrapulmonary tuberculosis was more common in patients with autoimmune disorders in the general population. Tuberculosis patients were older and had no other risk factors for developing the disease. The third study was made up of a cohort of 789 (January 1989–January 2009) SLE patients treated in the Autoimmune Diseases Unit of the Hospital Universitario Virgen del Rocío de Sevilla, comparing patients with and without tuberculosis.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> They found 13 cases, with 61% having extrapulmonary forms. Overall mortality attributed to this infection was 30.8% and the frequency of tuberculosis was higher than that in the general population. However, although patients treated with higher doses of corticosteroids had more severe forms of the disease, no statistically significant differences were seen with other immunosuppressive therapies or greater frequency of renal involvement.The problem of the different epidemiological studies that have been conducted so far is that most are retrospective, introduce selection bias, and do not take into account socio-economic conditions.With respect to the diagnosis and treatment of latent tuberculosis, general recommendations, according to the American Thoracic Society,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> consider the need for treatment with isoniazid for 9 months when the skin reaction (TST) is ≥10mm in patients with diseases that increase the risk of developing the infection, and ≥5mm in all those receiving more than 15mg of prednisone daily or its equivalent. It also recommended annual TST for all persons whose social condition merited it or presented an increased risk of active tuberculosis during certain time periods or in the foreseeable future.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> This risk is well established for certain groups of patients, but not known exactly in lupus patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In Spain, the Society of Clinical Microbiology and Infectious Diseases, along with the Society of Pneumology and Thoracic Surgery (SEPAR), recently published a consensus document on recommendations for diagnosis, treatment and prevention of tuberculosis.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> This document contains the instructions for the TST (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), in which patients with prolonged immunosuppressive therapy are included, and with causes associated with false negatives, such as prolonged corticosteroid therapy (≥15mg of prednisone for more than one month), and any immunosuppressive chemotherapy (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Today, new tuberculosis diagnostic techniques are being introduced into clinical practice guidelines from various societies, but their role in the various risk groups is yet to be determined. They are based on the detection of gamma interferon in the blood (interferon gamma release assay [IGRA]), which is released in response to in vitro stimulation of primed T-cells with specific antigens of M. tuberculosis. There are currently two commercialized tests: QuantiFERON®-TB Gold In-Tube, using ELISA, and T-SPOT®. TB, based on the ELISPOT<a class="elsevierStyleCrossRef" href="#bib0120">24</a> technique. The concordance rate between the two is high, but it seems that T-SPOT®. TB is more sensitive than QuantiFERON®-TB Gold In-Tube.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> At present, SEPAR recommends a Mantoux test for diagnosis of tuberculosis infection in immunocompromised patients, and if negative, the performance of an IGRA (to avoid false negatives due to immunosuppression). For SLE patients, some studies have been published using QuantiFERON®-TB Gold in areas of high prevalence of tuberculosis.<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a> Their authors have been struck by the high percentage of indeterminate results of this technique with respect to the general population, due to lymphocytopenia suffered by many of these patients and the degree of disease activity, so they recommend interpreting the results with caution. In Spain there are still no data.Despite the recommendations, and that the incidence of tuberculosis in lupus appears to be higher than in the general population,<a class="elsevierStyleCrossRefs" href="#bib0080">16–19</a> the relative risk of infectious reactivation has not been formally established in these patients,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> and therefore the use of isoniazid for treating latent tuberculosis in lupus patients is not formalized. Regarding this issue, two studies have been published in high TB prevalence areas, India<a class="elsevierStyleCrossRef" href="#bib0140">28</a> and Hong Kong.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> The first found a reduction in the prevalence of active tuberculosis in lupus patients following administration of isoniazid, 11%–2%. In the second there was no greater protection, which we believe was due to the wrong design and methodology, since isoniazid was administered intermittently depending on the steroid dose received by the patient.In conclusion, we can say that tuberculosis is currently one of the most common infectious problems worldwide, and it is especially necessary to detect the latent phase in patients with autoimmune diseases because of the risk of reactivation. Regarding patients with SLE and tuberculosis in Spain, there is little data and it is all retrospective, so we need prospective studies on incidence and more viable and diagnostic clinical trials to evaluate the risk/benefit of treatment of latent infection.<a class="elsevierStyleCrossRefs" href="#bib0030">6,17,25</a>Ethical ConsiderationsProtection of Persons and AnimalsNo experiments were performed on humans or animals.Data ConfidentialityPatient data do not appear in this article.Right to Privacy and Informed ConsentAuthors obtained informed consent from patients and/or subjects referred to in this paper. These are in the hands of the corresponding author.Conflict of InterestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "xres293721" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec277708" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres293722" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec277709" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical Considerations" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Protection of Persons and Animals" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Data Confidentiality" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Right to Privacy and Informed Consent" ] ] ] 5 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of Interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-03-15" "fechaAceptado" => "2012-06-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec277708" "palabras" => array:3 [ 0 => "Systemic lupus erythematosus" 1 => "Tuberculosis" 2 => "Human immunodeficiency virus infection" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec277709" "palabras" => array:3 [ 0 => "Lupus eritematoso sistémico" 1 => "Tuberculosis" 2 => "Infección por el virus de la inmunodeficiencia humana" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "There has recently been an increase in the incidence of patients with systemic lupus erythematosus (SLE) mainly due to earlier diagnosis, and increased survival. Tuberculosis in our country is one of the most prevalent infectious diseases, and one of the underlying causes would be HIV infection and increased immigration from areas with high tuberculosis prevalence; this phenomenon is truly important in patients with autoimmune diseases, as clinical presentation, severity and prognosis of tuberculosis are often different to that of immunocompetent patients. Studies of tuberculosis in patients with SLE are scarce and inconclusive, with many doubts existing about the performance or non-tuberculous prophylaxis in this population and the absence of a protocol due to lack of conclusive studies. New techniques for diagnosis of tuberculosis (IGRAs) may be useful in this population due to higher sensitivity than Mantoux, helping avoid false negatives." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "En la actualidad se ha detectado un aumento en la incidencia de pacientes con lupus eritematoso sistémico (LES) debido fundamentalmente a un diagnóstico más precoz, e incremento en la supervivencia de estos. La tuberculosis en nuestro país es una de las enfermedades infecciosas más prevalentes; como causa subyacente, entre otras, estarían la infección por VIH y el aumento de inmigrantes procedentes de áreas con alta prevalencia tuberculosa; este fenómeno es verdaderamente importante en los pacientes con enfermedades autoinmunes, ya que la presentación clínica, intensidad y pronóstico de la tuberculosis suelen ser diferentes a los de los pacientes inmunocompetentes. Los estudios sobre tuberculosis en paciente con LES son escasos y poco concluyentes, habiendo hoy en día muchas dudas sobre la realización o no de profilaxis tuberculosa en esta población y sin haberse establecido aún un protocolo de actuación por falta de estudios concluyentes al respecto. Las nuevas técnicas de diagnóstico de infección tuberculosa (IGRA) podrían ser útiles en esta población debido a su mayor sensibilidad respecto al Mantoux, evitando también los falsos negativos del mismo." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Arenas Miras MM, et al. La infección tuberculosa en pacientes con lupus eritematoso sistémico: situación en España. Reumatol Clin. 2013;9:369–372." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical Condition \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Relative Risk \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIV/AIDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100–500 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Silicosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0–4.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic renal failure/hemodialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.0–25.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yeyunoileal bypass \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27–63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Solid organ transplant</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiac \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20–74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Carcinoma of the head or neck \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab427648.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Relative Risk With Respect to the Population for the Development of Active Tuberculosis." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contacts of tuberculosis patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Persons with X rays suggestive of inactive tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Persons with clinical and/or radiological signs of tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Persons who, if infected and have a greater risk for the development of tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• HIV infection \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• IV drug users \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Homeless persons \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Foreigners from countries with high prevalence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immunosuppressive diseases: leukopenia, lymphoma, neoplasia, and others \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prolonged immunosuppressive therapy, anti-TNF-α and patients who are candidates for transplant \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with social and epidemiological risk of developing active tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Day care center workers \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Teaching staff \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Health staff \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Prison staff \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epidemiologic studies and antituberculosis control programs \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab427647.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications of Tuberculin Testing." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infections \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Viral: HIV; measles, varicella, mumps \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Bacterial: tuberculosis (severe form, located on serosal surfaces), typhoid fever, brucellosis, whooping cough, leprosy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vaccination with live viruses: measles, mumps, poliomyelitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic renal disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe malnutrition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphoid organ disease: lymphomas, leukemia, sarcoidosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prolonged treatment with steroids (≥15mg prednisone for over a month) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chemotherapy and immunosuppressive therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Younger than 6 months and elderly patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Technical and or incorrect interpretation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exposure of tuberculin to the light or heat or denaturalization due to reactant age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Window period for positivity of tuberculin test \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab427646.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Causes of a False Negative Result on the Tuberculin Test." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization. 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Review article

Tuberculosis in Patients With Systemic Lupus Erythematosus: Spain's Situation

La infección tuberculosa en pacientes con lupus eritematoso sistémico: situación en España

María del Mar Arenas Mirasa,

Corresponding author

mmararenas@hotmail.com

Corresponding author.

, Carmen Hidalgo Tenoriob, Juan Jimenez Alonsoa

a Servicio de Medicina Interna, Hospital Universitario Virgen de las Nieves, Granada, Spain

b Sección de Infecciosas, Hospital Universitario Virgen de las Nieves, Granada, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberculosis is the most common infectious disease in the world&#44; estimated at about 8 million new cases per year&#44; with 12 million existing cases&#44; involving a total of 20 million cases annually&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Consequently&#44; the general population is more exposed to the TB bacilli&#44; something particularly disturbing in immunocompromised persons&#44; including patients with systemic lupus erythematosus &#40;SLE&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and this phenomenon is exacerbated in developing countries that have detected a high incidence of extrapulmonary tuberculosis with high mortality<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> figures&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In Spain the actual incidence of tuberculosis in the general population is not well known due to&#44; among other causes&#44; underreporting and underdiagnosis&#44; especially among the elderly population&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In recent years there has been a decline in the number of reported cases&#44; reaching 5795 in 2007&#44; although it is estimated that approximately 30&#37;&#8211;40&#37; of cases are not reported&#44; so the numbers could be significantly higher&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> According to data from the National Epidemiological Surveillance Network&#44; the total number of cases reported in 2009 was 7652&#44; equivalent to a crude incidence rate of 16&#46;96 cases per 100<span class="elsevierStyleHsp" style=""></span>000 persons&#46; Communities with higher overall rates were Ceuta&#44; Galicia&#44; La Rioja and Melilla&#44; although the number of reported cases include Catalonia&#44; Andalusia&#44; and Madrid&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Currently&#44; the main causes of death in patients with lupus are cardiovascular<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> disorders and infections&#44; the latter predominating in several series&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The administration of steroids and cyclophosphamide are 2 of the main risk factors in the development of infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Differential diagnosis between infection and lupus flares is sometimes difficult&#44; but essential because delays in treatment of both processes are associated with increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Moreover&#44; TB simulates some of the findings of autoimmune diseases such as joint pain&#47;arthritis&#44; rash or presence of autoantibodies&#44; which poses a problem for the diagnosis of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In patients with SLE there are immunologic and genetic alterations that predispose them to the development of infections&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Among those described are a deficit in complement&#44; functional asplenia&#44; impaired phagocytic system or functional deficits in the activity of T cells&#44; with reduced cytotoxic T cells and alterations in the function of suppressor T cells&#44; determining increased susceptibility to infections by mycobacteria&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Added to this&#44; the use of immunosuppressive agents such as azathioprine&#44; cyclophosphamide or mycophenolate produces decreased T and B lymphocytes counts&#44; and the widespread use of corticosteroids blocks T cell proliferation&#44; cytotoxic T cells&#44; microbicidal activity and antigen-specific immune response&#44; producing a significant impairment of cellular immunity&#44; and increased risk of infection by intracellular pathogens such as <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#44; viruses of the herpes family and <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> among other pathogens such as Listeria spp&#46; and Nocardia spp&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In countries where TB is endemic there have been numerous studies in patients with lupus&#46; However&#44; in Spain these are scarce and inconclusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;16</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In a retrospective study comprising 390 patients with SLE from the Philippines&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> 13&#46;8&#37; had active tuberculosis&#44; and of these&#44; 74&#37; had only pulmonary involvement&#59; it also found that patients with disseminated infection had a higher lupus activity index and more aggressive disease&#44; regardless of the corticosteroid dose they were receiving at the time of diagnosis&#46; In another retrospective<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> study that included 283 SLE patients and 284 with rheumatoid arthritis from Korea&#44; it was found that the most common form of involvement was pulmonary tuberculosis and lupus&#44; mainly in patients with higher doses of corticosteroids&#46; Alongside this&#44; a greater percentage of extrapulmonary tuberculosis was described in lupus patients than in the general population&#44; up to 45&#37; of cases by one of the published series&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and the main risk factor was higher daily or cumulative doses of corticosteroids during the year before diagnosis&#44; more often for arthritis and renal involvement&#46; These findings were similar to those described by Tam et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> who conducted a case-control study in Hong Kong consisting of 526 patients with SLE an who provided analysis of the different risk factors involved in the development of active tuberculosis&#46; In this study&#44; a univariate analysis&#44; patients with SLE and cerebral involvement had higher rates of tuberculosis&#44; nephritis&#44; vasculitis&#44; cumulative dose of corticosteroids and intravenous methylprednisolone pulses relative to the control group&#46; In the multivariate analysis&#44; the presence of nephritis and the cumulative dose of corticosteroids were independent risk factors for developing the disease&#46; They also found an increase of extrapulmonary tuberculosis&#44; which together with the military for&#44; was the most common presentation in patients &#40;67&#37;&#41;&#46; The other risk factor independently associated with the occurrence of tuberculosis in patients with SLE was pleuritis&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">As for Spanish studies on tuberculosis in patients with lupus&#44; there have been three types so far&#46; The first was a retrospective study which consisted of patients with lupus treated in the Systemic Autoimmune Diseases Unit of the Hospital de Cruces in the Basque Country between 1994 and 2003&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In this&#44; the incidence of active tuberculosis in patients with SLE &#40;187 cases per 100<span class="elsevierStyleHsp" style=""></span>000&#41; was compared with the population of the area &#40;20&#8211;45 cases per 100<span class="elsevierStyleHsp" style=""></span>000&#41;&#44; which turned out to be much lower than that of patients with lupus&#44; and no predictor for the development of tuberculosis was identified among their patients&#46; The second&#44; also retrospective&#44; was held at the Rheumatology Service&#44; Hospital Clinico San Carlos in Madrid&#44; and was composed of patients diagnosed with autoimmune disease and tuberculosis treated at the Unit&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They found an incidence rate of tuberculosis in patients with autoimmune diseases of 153 cases per 100<span class="elsevierStyleHsp" style=""></span>000 patient-years&#44; which increased to 645 cases&#47;100<span class="elsevierStyleHsp" style=""></span>000 patient years when analyzing patients with SLE and vasculitis&#59; in that year the incidence of tuberculosis in the Autonomous Community of Madrid was 26 cases per 100<span class="elsevierStyleHsp" style=""></span>000 population per year&#44; concluding that extrapulmonary tuberculosis was more common in patients with autoimmune disorders in the general population&#46; Tuberculosis patients were older and had no other risk factors for developing the disease&#46; The third study was made up of a cohort of 789 &#40;January 1989&#8211;January 2009&#41; SLE patients treated in the Autoimmune Diseases Unit of the Hospital Universitario Virgen del Roc&#237;o de Sevilla&#44; comparing patients with and without tuberculosis&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> They found 13 cases&#44; with 61&#37; having extrapulmonary forms&#46; Overall mortality attributed to this infection was 30&#46;8&#37; and the frequency of tuberculosis was higher than that in the general population&#46; However&#44; although patients treated with higher doses of corticosteroids had more severe forms of the disease&#44; no statistically significant differences were seen with other immunosuppressive therapies or greater frequency of renal involvement&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The problem of the different epidemiological studies that have been conducted so far is that most are retrospective&#44; introduce selection bias&#44; and do not take into account socio-economic conditions&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">With respect to the diagnosis and treatment of latent tuberculosis&#44; general recommendations&#44; according to the American Thoracic Society&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> consider the need for treatment with isoniazid for 9 months when the skin reaction &#40;TST&#41; is &#8805;10<span class="elsevierStyleHsp" style=""></span>mm in patients with diseases that increase the risk of developing the infection&#44; and &#8805;5<span class="elsevierStyleHsp" style=""></span>mm in all those receiving more than 15<span class="elsevierStyleHsp" style=""></span>mg of prednisone daily or its equivalent&#46; It also recommended annual TST for all persons whose social condition merited it or presented an increased risk of active tuberculosis during certain time periods or in the foreseeable future&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> This risk is well established for certain groups of patients&#44; but not known exactly in lupus patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In Spain&#44; the Society of Clinical Microbiology and Infectious Diseases&#44; along with the Society of Pneumology and Thoracic Surgery &#40;SEPAR&#41;&#44; recently published a consensus document on recommendations for diagnosis&#44; treatment and prevention of tuberculosis&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> This document contains the instructions for the TST &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; in which patients with prolonged immunosuppressive therapy are included&#44; and with causes associated with false negatives&#44; such as prolonged corticosteroid therapy &#40;&#8805;15<span class="elsevierStyleHsp" style=""></span>mg of prednisone for more than one month&#41;&#44; and any immunosuppressive chemotherapy &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Today&#44; new tuberculosis diagnostic techniques are being introduced into clinical practice guidelines from various societies&#44; but their role in the various risk groups is yet to be determined&#46; They are based on the detection of gamma interferon in the blood &#40;interferon gamma release assay &#91;IGRA&#93;&#41;&#44; which is released in response to in vitro stimulation of primed T-cells with specific antigens of <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; There are currently two commercialized tests&#58; QuantiFERON<span class="elsevierStyleSup">&#174;</span>-TB Gold In-Tube&#44; using ELISA&#44; and T-SPOT<span class="elsevierStyleSup">&#174;</span>&#46; TB&#44; based on the ELISPOT<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> technique&#46; The concordance rate between the two is high&#44; but it seems that T-SPOT<span class="elsevierStyleSup">&#174;</span>&#46; TB is more sensitive than QuantiFERON<span class="elsevierStyleSup">&#174;</span>-TB Gold In-Tube&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> At present&#44; SEPAR recommends a Mantoux test for diagnosis of tuberculosis infection in immunocompromised patients&#44; and if negative&#44; the performance of an IGRA &#40;to avoid false negatives due to immunosuppression&#41;&#46; For SLE patients&#44; some studies have been published using QuantiFERON<span class="elsevierStyleSup">&#174;</span>-TB Gold in areas of high prevalence of tuberculosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> Their authors have been struck by the high percentage of indeterminate results of this technique with respect to the general population&#44; due to lymphocytopenia suffered by many of these patients and the degree of disease activity&#44; so they recommend interpreting the results with caution&#46; In Spain there are still no data&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Despite the recommendations&#44; and that the incidence of tuberculosis in lupus appears to be higher than in the general population&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;19</span></a> the relative risk of infectious reactivation has not been formally established in these patients&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and therefore the use of isoniazid for treating latent tuberculosis in lupus patients is not formalized&#46; Regarding this issue&#44; two studies have been published in high TB prevalence areas&#44; India<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and Hong Kong&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The first found a reduction in the prevalence of active tuberculosis in lupus patients following administration of isoniazid&#44; 11&#37;&#8211;2&#37;&#46; In the second there was no greater protection&#44; which we believe was due to the wrong design and methodology&#44; since isoniazid was administered intermittently depending on the steroid dose received by the patient&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; we can say that tuberculosis is currently one of the most common infectious problems worldwide&#44; and it is especially necessary to detect the latent phase in patients with autoimmune diseases because of the risk of reactivation&#46; Regarding patients with SLE and tuberculosis in Spain&#44; there is little data and it is all retrospective&#44; so we need prospective studies on incidence and more viable and diagnostic clinical trials to evaluate the risk&#47;benefit of treatment of latent infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;17&#44;25</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical Considerations</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of Persons and Animals</span><p id="par0070" class="elsevierStylePara elsevierViewall">No experiments were performed on humans or animals&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Data Confidentiality</span><p id="par0075" class="elsevierStylePara elsevierViewall">Patient data do not appear in this article&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to Privacy and Informed Consent</span><p id="par0080" class="elsevierStylePara elsevierViewall">Authors obtained informed consent from patients and&#47;or subjects referred to in this paper&#46; These are in the hands of the corresponding author&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2012-03-15"
    "fechaAceptado" => "2012-06-21"
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          "clase" => "keyword"
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            0 => "Systemic lupus erythematosus"
            1 => "Tuberculosis"
            2 => "Human immunodeficiency virus infection"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec277709"
          "palabras" => array:3 [
            0 => "Lupus eritematoso sist&#233;mico"
            1 => "Tuberculosis"
            2 => "Infecci&#243;n por el virus de la inmunodeficiencia humana"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There has recently been an increase in the incidence of patients with systemic lupus erythematosus &#40;SLE&#41; mainly due to earlier diagnosis&#44; and increased survival&#46; Tuberculosis in our country is one of the most prevalent infectious diseases&#44; and one of the underlying causes would be HIV infection and increased immigration from areas with high tuberculosis prevalence&#59; this phenomenon is truly important in patients with autoimmune diseases&#44; as clinical presentation&#44; severity and prognosis of tuberculosis are often different to that of immunocompetent patients&#46; Studies of tuberculosis in patients with SLE are scarce and inconclusive&#44; with many doubts existing about the performance or non-tuberculous prophylaxis in this population and the absence of a protocol due to lack of conclusive studies&#46; New techniques for diagnosis of tuberculosis &#40;IGRAs&#41; may be useful in this population due to higher sensitivity than Mantoux&#44; helping avoid false negatives&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En la actualidad se ha detectado un aumento en la incidencia de pacientes con lupus eritematoso sist&#233;mico &#40;LES&#41; debido fundamentalmente a un diagn&#243;stico m&#225;s precoz&#44; e incremento en la supervivencia de estos&#46; La tuberculosis en nuestro pa&#237;s es una de las enfermedades infecciosas m&#225;s prevalentes&#59; como causa subyacente&#44; entre otras&#44; estar&#237;an la infecci&#243;n por VIH y el aumento de inmigrantes procedentes de &#225;reas con alta prevalencia tuberculosa&#59; este fen&#243;meno es verdaderamente importante en los pacientes con enfermedades autoinmunes&#44; ya que la presentaci&#243;n cl&#237;nica&#44; intensidad y pron&#243;stico de la tuberculosis suelen ser diferentes a los de los pacientes inmunocompetentes&#46; Los estudios sobre tuberculosis en paciente con LES son escasos y poco concluyentes&#44; habiendo hoy en d&#237;a muchas dudas sobre la realizaci&#243;n o no de profilaxis tuberculosa en esta poblaci&#243;n y sin haberse establecido a&#250;n un protocolo de actuaci&#243;n por falta de estudios concluyentes al respecto&#46; Las nuevas t&#233;cnicas de diagn&#243;stico de infecci&#243;n tuberculosa &#40;IGRA&#41; podr&#237;an ser &#250;tiles en esta poblaci&#243;n debido a su mayor sensibilidad respecto al Mantoux&#44; evitando tambi&#233;n los falsos negativos del mismo&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Arenas Miras MM&#44; et al&#46; La infecci&#243;n tuberculosa en pacientes con lupus eritematoso sist&#233;mico&#58; situaci&#243;n en Espa&#241;a&#46; Reumatol Clin&#46; 2013&#59;9&#58;369&#8211;372&#46;</p>"
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Solid organ transplant</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cardiac&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">20&#8211;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Carcinoma of the head or neck</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Persons with clinical and&#47;or radiological signs of tuberculosis</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Immunosuppressive diseases&#58; leukopenia&#44; lymphoma&#44; neoplasia&#44; and others</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Prolonged immunosuppressive therapy&#44; anti-TNF-&#945; and patients who are candidates for transplant</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8226; Bacterial&#58; tuberculosis &#40;severe form&#44; located on serosal surfaces&#41;&#44; typhoid fever&#44; brucellosis&#44; whooping cough&#44; leprosy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Chronic renal disease</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Severe malnutrition</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Prolonged treatment with steroids &#40;&#8805;15</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg prednisone for over a month&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Chemotherapy and immunosuppressive therapy</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Younger than 6 months and elderly patients</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Technical and or incorrect interpretation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exposure of tuberculin to the light or heat or denaturalization due to reactant age</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Window period for positivity of tuberculin test</span>&nbsp;\t\t\t\t\t\t\n
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              "identificador" => "bib0005"
              "etiqueta" => "1"
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                  "referenciaCompleta" => "World Health Organization&#46; Global tuberculosis control-epidemiology&#44; strategy&#44; financing &#40;up date 2009&#41;&#46; Available from&#58; <a class="elsevierStyleInterRef" href="http://www.who.int/tb/publications/global_report/2009/update/en/index.htlm">http&#58;&#47;&#47;www&#46;who&#46;int&#47;tb&#47;publications&#47;global&#95;report&#47;2009&#47;update&#47;en&#47;index&#46;htlm</a> &#91;accessed 19&#46;09&#46;09&#93;&#46;"
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                    0 => array:2 [
                      "titulo" => "Infections and SLE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Zandman-Goddard"
                            1 => "Y&#46; Shoenfeld"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/08916930500285352"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autoimmunity"
                        "fecha" => "2005"
                        "volumen" => "38"
                        "paginaInicial" => "473"
                        "paginaFinal" => "485"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16373252"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
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              ]
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              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "High risk of tuberculosis in systemic lupus erythematosus&#63;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;G&#46; Erdozain"
                            1 => "G&#46; Ruiz-Irastorza"
                            2 => "M&#46;V&#46; Egurbide"
                            3 => "A&#46; Martinez-Berriotxoa"
                            4 => "C&#46; Aguirre"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lupus"
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                        "paginaInicial" => "232"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16686263"
                            "web" => "Medline"
                          ]
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            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidencia y caracter&#237;sticas de la tuberculosis en pacientes con enfermedades reum&#225;ticas autoinmunes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Vadillo Font"
                            1 => "C&#46; Hern&#225;ndez-Garc&#237;a"
                            2 => "E&#46; Pato"
                            3 => "I&#46;C&#46; Morado"
                            4 => "M&#46; Salido"
                            5 => "E&#46; J&#250;dez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Clin Esp"
                        "fecha" => "2003"
                        "volumen" => "203"
                        "paginaInicial" => "178"
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                          0 => array:2 [
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2012.06.026

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	15	11	26
2024 October	123	72	195
2024 September	113	26	139
2024 August	136	35	171
2024 July	153	56	209
2024 June	148	62	210
2024 May	113	59	172
2024 April	118	33	151
2024 March	124	54	178
2024 February	80	26	106
2024 January	95	34	129
2023 December	93	42	135
2023 November	102	36	138
2023 October	126	65	191
2023 September	183	48	231
2023 August	88	19	107
2023 July	87	47	134
2023 June	105	47	152
2023 May	115	47	162
2023 April	75	36	111
2023 March	134	46	180
2023 February	108	45	153
2023 January	93	37	130
2022 December	81	56	137
2022 November	137	35	172
2022 October	106	42	148
2022 September	90	55	145
2022 August	91	50	141
2022 July	83	51	134
2022 June	94	38	132
2022 May	104	69	173
2022 April	106	58	164
2022 March	105	49	154
2022 February	122	60	182
2022 January	97	44	141
2021 December	59	39	98
2021 November	81	59	140
2021 October	109	61	170
2021 September	105	53	158
2021 August	97	45	142
2021 July	66	36	102
2021 June	52	37	89
2021 May	93	51	144
2021 April	210	109	319
2021 March	142	46	188
2021 February	94	27	121
2021 January	88	29	117
2020 December	99	28	127
2020 November	78	50	128
2020 October	76	25	101
2020 September	103	23	126
2020 August	54	19	73
2020 July	51	24	75
2020 June	67	23	90
2020 May	67	5	72
2020 April	64	45	109
2020 March	20	5	25
2020 February	1	0	1
2020 January	2	0	2
2019 September	2	0	2
2019 June	1	0	1
2019 April	3	2	5
2019 January	1	0	1
2018 May	9	0	9
2018 April	97	11	108
2018 March	83	14	97
2018 February	65	8	73
2018 January	82	12	94
2017 December	66	11	77
2017 November	115	21	136
2017 October	94	8	102
2017 September	88	7	95
2017 August	108	9	117
2017 July	109	9	118
2017 June	140	16	156
2017 May	195	18	213
2017 April	165	16	181
2017 March	193	12	205
2017 February	136	3	139
2017 January	115	16	131
2016 December	233	21	254
2016 November	238	11	249
2016 October	254	19	273
2016 September	350	10	360
2016 August	343	10	353
2016 July	208	19	227
2016 April	1	0	1
2015 December	2	0	2
2015 October	1	0	1
2015 September	5	0	5
2015 July	71	13	84
2015 June	97	14	111
2015 May	147	24	171
2015 April	152	19	171
2015 March	123	9	132
2015 February	140	9	149
2015 January	117	9	126
2014 December	143	9	152
2014 November	118	11	129
2014 October	174	17	191
2014 September	80	14	94
2014 August	60	12	72
2014 July	71	16	87
2014 June	78	16	94
2014 May	85	25	110
2014 April	60	13	73
2014 March	90	20	110
2014 February	49	16	65
2014 January	63	21	84
2013 December	65	30	95
2013 November	17	4	21

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