Ultrasound in the diagnosis of asymptomatic hyperuricemia and gout

García Puig, J.; Beltrán, L.; Mejía Chew, C.; Torres, R.; Tebar Márquez, D.; Pose Reino, A.

doi:10.1016/j.rceng.2016.06.004

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A) Obtención de una imagen longitudinal ecográfica del cartílago femoral. B) Sujeto sano; la línea inferior corresponde a la cortical ósea en contacto con el cartílago hialino. La línea superior corresponde a la superficie del cartílago hialino expuesta al líquido sinovial. C) Signo del doble contorno en el paciente con hiperuricemia asintomática descrito en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>. La línea hiperecoica superior se debe al depósito de UMS sobre el cartílago hialino. D) Imagen longitudinal ecográfica de la primera articulación metatarsofalángica en el paciente con gota, aparentemente no tofácea, descrito en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>. E) Línea hiperecoica irregular (flechas) que corresponde a la cortical ósea. Se aprecia un área hiperecoica («hyperechoic cloudy area», línea de puntos) debida al depósito de UMS (tofo). Sobre esta área se aprecia un halo circundante anecoico (puntas de flechas). F) Señal doppler («árbol de Navidad») sugestiva de respuesta inflamatoria importante." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. García Puig, L. Beltrán, C. Mejía Chew, R. Torres, D. Tebar Márquez, A. Pose Reino" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "García Puig" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Beltrán" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Mejía Chew" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Torres" ] 4 => array:2 [ "nombre" => "D." "apellidos" => "Tebar Márquez" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Pose Reino" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887416300327" "doi" => "10.1016/j.rceng.2016.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887416300327?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256516300807?idApp=WRCEE" "url" => "/00142565/0000021600000008/v1_201610290716/S0014256516300807/v1_201610290716/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2254887416300248" "issn" => "22548874" "doi" => "10.1016/j.rceng.2016.05.001" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "1259" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2016;216:436-44" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2 "PDF" => 2 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Update on pulmonary arterial hypertension" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "436" "paginaFinal" => "444" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización en hipertensión arterial pulmonar" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C.R. Mejía Chew, S.A. Batres, J.J. Ríos Blanco" "autores" => array:3 [ 0 => array:2 [ "nombre" => "C.R." "apellidos" => "Mejía Chew" ] 1 => array:2 [ "nombre" => "S.A." "apellidos" => "Batres" ] 2 => array:2 [ "nombre" => "J.J." 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García Puig, L. Beltrán, C. Mejía Chew, R. Torres, D. Tebar Márquez, A. Pose Reino" "autores" => array:6 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "García Puig" "email" => array:1 [ 0 => "juangarciapuig@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Beltrán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Mejía Chew" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Torres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "D." "apellidos" => "Tebar Márquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Pose Reino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad Metabólico-Vascular, Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Bioquímica Clínica, Instituto de Investigación Sanitaria, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La ecografía en el diagnóstico de la hiperuricemia asintomática y la gota" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 821 "Ancho" => 1750 "Tamanyo" => 172735 ] ] "descripcion" => array:1 [ "en" => "Main ultrasound findings indicative of monosodium urate deposits (MUS) in the patients referenced in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. (A) Obtaining an ultrasound longitudinal image of the femoral cartilage. (B) Healthy patient; the lower line corresponds to the cortical bone touching the hyaline cartilage. The upper line corresponds to the surface of the hyaline cartilage exposed to the synovial liquid. (C) Double contour sign in the patient with asymptomatic hyperuricemia described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The upper hyperechoic line is due to the MUS deposit on the hyaline cartilage. (D) Ultrasound longitudinal image of the first metatarsophalangeal joint in the patient with gout, apparently not tophaceous, described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. (E) Irregular hyperechoic line (arrows) corresponding to the cortical bone. A hyperechoic cloudy area (line of points) can be observed and is due to the MUS deposit (tophus). An anechoic surrounding halo (points of arrows) can be observed. (F) Doppler signal (“Christmas tree”) suggestive of significant inflammatory response." ] ] ] "textoCompleto" => "Hyperuricemia is an increase in serum monosodium urate (MSU) (uric acid) concentrations. Gout is secondary to the inflammatory response that provokes MSU deposits in the tissue. Gout is the most common inflammatory arthropathy in the general population. The prevalence of hyperuricemia and gout increases with age and depends on the study population. In the general population of Madrid, the prevalence of hyperuricemia (>7mg/dL) is 11.3% (95% confidence interval [95% CI] 8.3–13.9%).<a class="elsevierStyleCrossRef" href="#bib0170">1</a> The prevalence rate of metabolic syndrome was 53.1% for the patients with hyperuricemia and 24.4% for the patients with normal uricemia levels (p<.001).<a class="elsevierStyleCrossRef" href="#bib0170">1</a> Serum MSU concentrations are significantly related to all components of metabolic syndrome (obesity, blood pressure, reduction in HDL, increase in triglyceride and glucose levels), but the most intense direct relationship was with abdominal circumference (r, 0.455; p<.001).<a class="elsevierStyleCrossRef" href="#bib0170">1</a>The prevalence rate of gout reaches 7% in men older than 75 years and 3% in women older than 85 years.<a class="elsevierStyleCrossRef" href="#bib0175">2</a> It has been estimated that the life years with disability attributable to gout have increased from 76,000 (95% CI 48–112) in 1990 to 114,000 (95% CI 72–167) in 2010.<a class="elsevierStyleCrossRef" href="#bib0175">2</a> This increase in the prevalence of hyperuricemia and gout could be related to the epidemic of excess weight and obesity in developed countries and with the dietary changes that tend toward an increased consumption of food rich in purines, alcoholic beverages (beer) and soft drinks sweetened with fructose.<a class="elsevierStyleCrossRefs" href="#bib0180">3,4</a> In most patients, the increase in serum MSU concentrations is due to a reduction in the renal excretion of uric acid,<a class="elsevierStyleCrossRefs" href="#bib0190">5,6</a> which, in many cases, is caused by a change in the function of certain renal<a class="elsevierStyleCrossRefs" href="#bib0195">6,7</a> and intestinal transporters.<a class="elsevierStyleCrossRef" href="#bib0205">8</a> Hyperuricemia not only entails an increased risk of gout but also has been associated with heart and kidney disease and can be an expression of generalized arteriosclerosis.<a class="elsevierStyleCrossRef" href="#bib0210">9</a> For many years, significant circadian variations have been reported in blood MSU concentrations, in opposition to the circadian changes in nitric oxide. These variations could not only be relevant to the pathophysiology of related diseases but also have chronotherapeutic implications in the management of hyperuricemia-related diseases.<a class="elsevierStyleCrossRef" href="#bib0215">10</a> It seems appropriate therefore to determine the phase or stage of a patient with hyperuricemia or gout, in its entirety.Clinical stages of hyperuricemia and goutAll diseases go through various evolutionary stages, resulting in the diversity of clinical manifestations. The most typical clinical expression of gout is acute inflammatory attacks (<24h) that involve the first metatarsophalangeal joint of the big toe (podagra).<a class="elsevierStyleCrossRef" href="#bib0220">11</a> The initial presentation can affect other joints such as the forefoot, ankles, knees, elbows, wrists, metacarpophalangeals and interphalangeals.<a class="elsevierStyleCrossRef" href="#bib0225">12</a> The pathogenesis of the inflammatory process lies in the phagocytosis of MSU crystal, deposited in the joints (microtophi), which can remain asymptomatic for many years.Various imaging techniques have shown that numerous patients with asymptomatic and apparently nontophaceous hyperuricemia (ultrasonography, dual-energy computed tomography) or gout (plain radiography, computed tomography or dual-energy computed tomography, magnetic resonance imaging, ultrasonography) have MSU deposits (microtophi).<a class="elsevierStyleCrossRef" href="#bib0230">13</a>Ultrasonography, due to its accessibility in clinical practice, has been the most studied imaging test in this context. The findings result from the presence of MSU deposits in the subcutaneous tissue and in the intrajoint and perijoint areas (cartilage, tendons, ligaments and bursae). There are 2 specific findings of MSU deposits: (1) echogenic enhancement of the chondrosynovial margin of the cartilage, regardless of the insonation angle (double contour sign) and (2) the presence of hyperechoic aggregates, which in turn can have 3 types of presentation: hyperechoic points (<1mm) within a joint effusion; homogeneous “cottony areas” (<1cm) without a posterior acoustic shadow; and larger heterogeneous tophi, with calcifications and posterior acoustic shadow.<a class="elsevierStyleCrossRefs" href="#bib0235">14,15</a>Numerous studies have investigated the areas in which ultrasonography should be performed to obtain the best sensitivity and specificity in detecting MSU deposits. Naredo et al. demonstrated that the examination of 12 anatomical areas provided the highest sensitivity and specificity.<a class="elsevierStyleCrossRef" href="#bib0245">16</a> However, such an extensive examination can be difficult to incorporate into standard clinical practice. The approach proposed by Peitado et al. is more practical and includes the bilateral examination of the knees and metatarsophalangeals, which helps detect ultrasound signs of gout in 97% of cases.<a class="elsevierStyleCrossRef" href="#bib0250">17</a>This ultrasound-generated information has helped to suggest a new classification of hyperuricemia and gout into 4 stages (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0255">18</a> As discussed below, the information offered by ultrasonography can represent a conceptual revolution in the diagnosis and treatment of hyperuricemia and gout.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Asymptomatic hyperuricemia: a benign entity?Asymptomatic hyperuricemia is frequently associated with disorders that increase vascular risk (obesity, arterial hypertension, diabetes, dyslipidemia and metabolic syndrome)<a class="elsevierStyleCrossRef" href="#bib0255">18</a> and has also been postulated as an independent vascular risk factor.<a class="elsevierStyleCrossRef" href="#bib0260">19</a> Regardless of its etiopathogenesis, asymptomatic hyperuricemia is considered a benign entity that only occasionally progresses to gout. The probability of this progression is proportional to serum MSU concentrations and to their time of evolution. When uricemia levels are ≥10mg/dL, gout is produced after 5 years in approximately 50% of patients.<a class="elsevierStyleCrossRef" href="#bib0265">20</a> The European and American guidelines do not recommend hypouricemic treatment for patients with asymptomatic hyperuricemia.<a class="elsevierStyleCrossRefs" href="#bib0270">21–24</a> Years ago, we proposed the hypothesis that prolonged high uricemia levels (≥7mg/dL, solubility limit in serum) could cause MSU crystals and subsequent inflammation. We documented for the first time that 1/3 of patients with asymptomatic hyperuricemia had silent MSU deposits (microtophi) and that 25% of these patients showed ultrasound signs of inflammation<a class="elsevierStyleCrossRef" href="#bib0290">25</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, case of asymptomatic hyperuricemia) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Subsequently, 3 additional studies in patients with prolonged asymptomatic hyperuricemia (≥2 years) confirmed that 34–42% of the patients had MSU deposits and 24% had inflammation in the Doppler study.<a class="elsevierStyleCrossRefs" href="#bib0295">26–28</a> Lastly, a recent study observed that the ultrasound presence of MSU deposits in patients with asymptomatic hyperuricemia was associated with an increased degree of coronary calcification. The authors indicated that this finding was due to the inflammation mediated by the MSU crystal deposits, a plausible but still unconfirmed explanation.<a class="elsevierStyleCrossRef" href="#bib0310">29</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>These observations raise 2 important questions: (1) if a patient with “asymptomatic hyperuricemia” (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, A) has tophi in the imaging techniques, should they be considered a patient with asymptomatic gout (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, B)? and (2) if a patient with hyperuricemia and asymptomatic tophi has ultrasound signs of inflammation (Doppler), should they be treated with hypouricemic drugs?If the answer to both questions is yes, then we are faced with a large paradigm shift: conducting joint ultrasonography would be appropriate for all patients with long-standing asymptomatic hyperuricemia, as in the case referred to in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The findings and treatment could well change the clinical course of “asymptomatic hyperuricemia”, which would completely diverge from the course currently advocated by the European and American guidelines.<a class="elsevierStyleCrossRefs" href="#bib0270">21–24</a> In this respect, we should emphasize that the therapeutic indication approved by the European Medicines Agency for febuxostat (the second marketed inhibitor of the enzyme xanthine oxidase, after allopurinol) is literally: “treatment of the chronic hyperuricemia in conditions of urate deposits.” This approach would enable starting hypouricemic treatment regardless of finding acute gout attacks. Taking this measure, however, requires clinical trials that show its benefit. The management of the necessary resources for conducting joint ultrasonography of all patients with relevant hyperuricemia (≥8mg/dL) over an extended period of time (e.g. ≥2 years) is acceptable, given that an abbreviated version of this examination can be performed in less than 10min.<a class="elsevierStyleCrossRef" href="#bib0250">17</a> Nevertheless, prospective studies need to be conducted to answer these questions.Gout: tophaceous or nontophaceous?Clinicians know that disease manifestations depend, in considerable measure, to observer acumen and the availability of additional tests. In a review of 14 studies, approximately half of the patients with gout showed tophi when examined with ultrasonography.<a class="elsevierStyleCrossRef" href="#bib0315">30</a> Therefore, the clinical diagnosis of “nontophaceous gout” (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, C) is currently questionable if ultrasonography is not performed. What would be the result of performing ultrasound examinations of knees and metatarsophalangeal joints for all patients with gout? Two apparent benefits of this approach are that (1) it would modify the classification (a patient with nontophaceous gout would be reclassified into the tophaceous gout group [<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, C would move to D]) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, case report of gout) and (2) the hypouricemic treatment of patients with urate deposits would change in 2 ways. First, we would ensure a uricemic level below 5mg/dL to achieve complete reabsorption of the tophi as soon as possible.<a class="elsevierStyleCrossRef" href="#bib0270">21</a> Even at 2 years from the start of hypouricemic treatment, numerous patients with gout have tophi and signs of inflammation.<a class="elsevierStyleCrossRef" href="#bib0320">31</a> Second, the finding of tophi and signs of inflammation requires that appropriate prophylaxis be added to the hypouricemic treatment to prevent acute inflammation attacks, presumably triggered by the reabsorption of urate crystals.<a class="elsevierStyleCrossRef" href="#bib0325">32</a> When tophi are detected, the ultrasound follow-up helps determine its progression and establish the intensity of the hypouricemic treatment, the most advisable uricemia concentrations and whether it is appropriate to maintain a prophylactic treatment while there are tophi.<a class="elsevierStyleCrossRef" href="#bib0330">33</a> The current availability of ultrasonography leads us to the prediction that in the near future we will have the necessary studies to verify its potential apparent benefits resulting from its systematic use.One final thought: imaging techniques can help provide a better clinical classification of asymptomatic hyperuricemia and gout and perhaps a more rational treatment. However, it will never substitute good clinical judgment and individualized treatment. This is what constitutes the art of medicine.FundingThis study was the result of the research project “The internist's ultrasound” (La ecografía del internista), Biomedical Research Foundation of University Hospital La Paz, FIBHULP, PI 1471, and was made possible thanks to FIS (15/01000) and the Mutua Madrileña.Conflict of interestThe Metabolic-Vascular Unit of University Hospital La Paz is developing an educational program based on the practical teaching of clinical ultrasonography to medical internists and is being funded by Menarini Laboratories." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres750239" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec752993" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres750238" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec752994" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinical stages of hyperuricemia and gout" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Asymptomatic hyperuricemia: a benign entity?" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Gout: tophaceous or nontophaceous?" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-18" "fechaAceptado" => "2016-05-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec752993" "palabras" => array:4 [ 0 => "Gout" 1 => "Hyperuricemia" 2 => "Double contour sign" 3 => "Tophi" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec752994" "palabras" => array:4 [ 0 => "Gota" 1 => "Hiperuricemia" 2 => "Signo del doble contorno" 3 => "Tofos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The increase in serum urate concentrations (hyperuricemia, ≥7.0mg/dL) creates crystals, which promote inflammation and joint lesions. Ultrasonography can reveal these urate deposits. The presence of crystals suggests that a patient with hyperuricemia is actually experiencing asymptomatic gout, and that a patient with gout without subcutaneous tophi could experience tophaceous gout. The information offered by ultrasound (double contour sign and hyperechoic concretions mimicking clouds) enables a more specific classification of hyperuricemia and gout. Additionally, this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricemia and gout." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El aumento de la concentración sérica de uratos (hiperuricemia, mayor o igual a 7,0mg/dL) ocasiona cristales que promueven inflamación y lesión articular. La ecografía puede poner de manifiesto estos depósitos de urato. Su presencia obliga a considerar que un paciente con hiperuricemia en realidad padece gota asintomática, y que un enfermo con gota sin tofos subcutáneos puede tener gota tofácea. La información que ofrece la ecografía (signo del «doble contorno» y de concreciones hiperecogénicas simulando nubes) posibilita una clasificación de la hiperuricemia y de la gota más precisas. Además, esta información puede dar lugar a modificaciones relevantes en cuanto al proceder diagnóstico y terapéutico en los enfermos con hiperuricemia y gota." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: García Puig J, Beltrán L, Mejía Chew C, Torres R, Tebar Márquez D, Pose Reino A. La ecografía en el diagnóstico de la hiperuricemia asintomática y la gota. Rev Clin Esp. 2016;216:445–450." ] ] "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" => 821 "Ancho" => 1750 "Tamanyo" => 172735 ] ] "descripcion" => array:1 [ "en" => "Main ultrasound findings indicative of monosodium urate deposits (MUS) in the patients referenced in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. (A) Obtaining an ultrasound longitudinal image of the femoral cartilage. (B) Healthy patient; the lower line corresponds to the cortical bone touching the hyaline cartilage. The upper line corresponds to the surface of the hyaline cartilage exposed to the synovial liquid. (C) Double contour sign in the patient with asymptomatic hyperuricemia described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The upper hyperechoic line is due to the MUS deposit on the hyaline cartilage. (D) Ultrasound longitudinal image of the first metatarsophalangeal joint in the patient with gout, apparently not tophaceous, described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. (E) Irregular hyperechoic line (arrows) corresponding to the cortical bone. A hyperechoic cloudy area (line of points) can be observed and is due to the MUS deposit (tophus). An anechoic surrounding halo (points of arrows) can be observed. (F) Doppler signal (“Christmas tree”) suggestive of significant inflammatory response." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperuricemia \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(A) Patients with increased serum urate concentrations, with no ultrasound evidence of monosodium urate deposits (e.g., heart failure and metabolic syndrome) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(B) Patients with increased serum urate concentrations, with ultrasound evidence of monosodium urate deposits (e.g., the same patients as in A with “microtophi”) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1239641.png" ] ] 1 => 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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gout \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(C) Patients who report an attack characteristic of gout, with no ultrasound evidence of monosodium urate deposits \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(D) Patients who report an attack characteristic of gout, with ultrasound evidence of monosodium urate deposits (“tophi” or “microtophi”) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1239642.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical stages into which patients with hyperuricemia or gout can be reclassified through joint ultrasonography." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 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"><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Asymptomatic hyperuricemia</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Case report \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Software engineer who consulted the doctor for obesity at 23 years of age (103kg, height 180cm). The patient was diagnosed with nonautoimmune hypothyroidism and treated with replacement therapy until normal thyroid function was achieved. Over the next 7 years, the patient's urate levels ranged from 7.7 to 12.5mg/dL (mean of 21 readings, 9.4mg/dL). The patient had never had joint pain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ultrasound findings \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The joint ultrasound of the knees revealed the “double contour sign” (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The metatarsophalangeal joint of the right foot showed tophaceous deposits with a positive Doppler sign; both are unequivocal signs of monosodium urate deposits (tophi). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Considerations</td><td class="td" title="table-entry " align="left" valign="top">Should the patient be diagnosed with “asymptomatic hyperuricemia” (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, A), or should the correct diagnosis be asymptomatic gout/tophaceous gout (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, B or D)? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Should we start hypouricemic treatment to reduce the urate deposits and inflammation, considering the patient is only 31 years old and that life expectancy in our community is approximately 50 additional years? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">What is the therapeutic objective, uricemia <5 or <6mg/dL? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">How long should prophylaxis be maintained to prevent an acute gouty arthritis attack? Until we achieve the established uricemia objective or until the urate deposits disappear in the follow-up ultrasound? \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1239643.png" ] ] 1 => 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"><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Gout</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Case report \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sixty-five-year-old mining engineer diagnosed with obesity, isolated systolic arterial hypertension, moderate left ventricular hypertrophy and microalbuminuria, 2 lacunar strokes with no neurological sequela, obstructive sleep apnea syndrome (OSAS) and metabolic syndrome (normal HDL). At 11pm after an extended train trip, the patient was awoken by acute pain in the big toe of the right foot, which almost prevented ambulation. The next day, the patient was transferred to a healthcare center where inflammatory signs were observed in the distal interphalangeal joint, as well as uricemia of 6.4mg/dL. No clinical subcutaneous tophi were detected. The inflammation improved with treatment in 24h. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ultrasound findings \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The interphalangeal joint ultrasound of the big toe of the foot right showed a heterogeneous nodular image, with hyperechoic areas and underlying bone erosions with peripheral Doppler uptake (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Considerations</td><td class="td" title="table-entry " align="left" valign="top">Should the patient be diagnosed with “nontophaceous gout” (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, C), based on the classical criteria for establishing the diagnosis of gout, with the “prefix” nontophaceous because tophi have not been found during the physical examination, or should the correct diagnosis in this case be “tophaceous gout” (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, D)? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">What is the therapeutic objective, uricemia <5 or <6mg/dL? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">How long should prophylaxis be maintained to prevent an acute gouty arthritis attack? Until we achieve the established uricemia objective or until the urate deposits disappear in the follow-up ultrasound? \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1239640.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Two cases studies to illustrate how ultrasound can modify the diagnosis and treatment of asymptomatic hyperuricemia and gout." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum urate, metabolic syndrome and cardiovascular risk factors. A population based study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.G. Puig" 1 => "M.A. Martínez" 2 => "M. Mora" 3 => "J.M. Fraile" 4 => "F. Montoya" 5 => "R.J. 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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hyperuricemia is an increase in serum monosodium urate &#40;MSU&#41; &#40;uric acid&#41; concentrations&#46; Gout is secondary to the inflammatory response that provokes MSU deposits in the tissue&#46; Gout is the most common inflammatory arthropathy in the general population&#46; The prevalence of hyperuricemia and gout increases with age and depends on the study population&#46; In the general population of Madrid&#44; the prevalence of hyperuricemia &#40;&#62;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; is 11&#46;3&#37; &#40;95&#37; confidence interval &#91;95&#37; CI&#93; 8&#46;3&#8211;13&#46;9&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> The prevalence rate of metabolic syndrome was 53&#46;1&#37; for the patients with hyperuricemia and 24&#46;4&#37; for the patients with normal uricemia levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Serum MSU concentrations are significantly related to all components of metabolic syndrome &#40;obesity&#44; blood pressure&#44; reduction in HDL&#44; increase in triglyceride and glucose levels&#41;&#44; but the most intense direct relationship was with abdominal circumference &#40;<span class="elsevierStyleItalic">r</span>&#44; 0&#46;455&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence rate of gout reaches 7&#37; in men older than 75 years and 3&#37; in women older than 85 years&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> It has been estimated that the life years with disability attributable to gout have increased from 76&#44;000 &#40;95&#37; CI 48&#8211;112&#41; in 1990 to 114&#44;000 &#40;95&#37; CI 72&#8211;167&#41; in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> This increase in the prevalence of hyperuricemia and gout could be related to the epidemic of excess weight and obesity in developed countries and with the dietary changes that tend toward an increased consumption of food rich in purines&#44; alcoholic beverages &#40;beer&#41; and soft drinks sweetened with fructose&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">3&#44;4</span></a> In most patients&#44; the increase in serum MSU concentrations is due to a reduction in the renal excretion of uric acid&#44;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">5&#44;6</span></a> which&#44; in many cases&#44; is caused by a change in the function of certain renal<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6&#44;7</span></a> and intestinal transporters&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> Hyperuricemia not only entails an increased risk of gout but also has been associated with heart and kidney disease and can be an expression of generalized arteriosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a> For many years&#44; significant circadian variations have been reported in blood MSU concentrations&#44; in opposition to the circadian changes in nitric oxide&#46; These variations could not only be relevant to the pathophysiology of related diseases but also have chronotherapeutic implications in the management of hyperuricemia-related diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> It seems appropriate therefore to determine the phase or stage of a patient with hyperuricemia or gout&#44; in its entirety&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Clinical stages of hyperuricemia and gout</span><p id="par0015" class="elsevierStylePara elsevierViewall">All diseases go through various evolutionary stages&#44; resulting in the diversity of clinical manifestations&#46; The most typical clinical expression of gout is acute inflammatory attacks &#40;&#60;24<span class="elsevierStyleHsp" style=""></span>h&#41; that involve the first metatarsophalangeal joint of the big toe &#40;podagra&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> The initial presentation can affect other joints such as the forefoot&#44; ankles&#44; knees&#44; elbows&#44; wrists&#44; metacarpophalangeals and interphalangeals&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> The pathogenesis of the inflammatory process lies in the phagocytosis of MSU crystal&#44; deposited in the joints &#40;microtophi&#41;&#44; which can remain asymptomatic for many years&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Various imaging techniques have shown that numerous patients with asymptomatic and apparently nontophaceous hyperuricemia &#40;ultrasonography&#44; dual-energy computed tomography&#41; or gout &#40;plain radiography&#44; computed tomography or dual-energy computed tomography&#44; magnetic resonance imaging&#44; ultrasonography&#41; have MSU deposits &#40;microtophi&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Ultrasonography&#44; due to its accessibility in clinical practice&#44; has been the most studied imaging test in this context&#46; The findings result from the presence of MSU deposits in the subcutaneous tissue and in the intrajoint and perijoint areas &#40;cartilage&#44; tendons&#44; ligaments and bursae&#41;&#46; There are 2 specific findings of MSU deposits&#58; &#40;1&#41; echogenic enhancement of the chondrosynovial margin of the cartilage&#44; regardless of the insonation angle &#40;double contour sign&#41; and &#40;2&#41; the presence of hyperechoic aggregates&#44; which in turn can have 3 types of presentation&#58; hyperechoic points &#40;&#60;1<span class="elsevierStyleHsp" style=""></span>mm&#41; within a joint effusion&#59; homogeneous &#8220;cottony areas&#8221; &#40;&#60;1<span class="elsevierStyleHsp" style=""></span>cm&#41; without a posterior acoustic shadow&#59; and larger heterogeneous tophi&#44; with calcifications and posterior acoustic shadow&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Numerous studies have investigated the areas in which ultrasonography should be performed to obtain the best sensitivity and specificity in detecting MSU deposits&#46; Naredo et al&#46; demonstrated that the examination of 12 anatomical areas provided the highest sensitivity and specificity&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a> However&#44; such an extensive examination can be difficult to incorporate into standard clinical practice&#46; The approach proposed by Peitado et al&#46; is more practical and includes the bilateral examination of the knees and metatarsophalangeals&#44; which helps detect ultrasound signs of gout in 97&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">This ultrasound-generated information has helped to suggest a new classification of hyperuricemia and gout into 4 stages &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> As discussed below&#44; the information offered by ultrasonography can represent a conceptual revolution in the diagnosis and treatment of hyperuricemia and gout&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Asymptomatic hyperuricemia&#58; a benign entity&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Asymptomatic hyperuricemia is frequently associated with disorders that increase vascular risk &#40;obesity&#44; arterial hypertension&#44; diabetes&#44; dyslipidemia and metabolic syndrome&#41;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> and has also been postulated as an independent vascular risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> Regardless of its etiopathogenesis&#44; asymptomatic hyperuricemia is considered a benign entity that only occasionally progresses to gout&#46; The probability of this progression is proportional to serum MSU concentrations and to their time of evolution&#46; When uricemia levels are &#8805;10<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; gout is produced after 5 years in approximately 50&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> The European and American guidelines do not recommend hypouricemic treatment for patients with asymptomatic hyperuricemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">21&#8211;24</span></a> Years ago&#44; we proposed the hypothesis that prolonged high uricemia levels &#40;&#8805;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; solubility limit in serum&#41; could cause MSU crystals and subsequent inflammation&#46; We documented for the first time that 1&#47;3 of patients with asymptomatic hyperuricemia had silent MSU deposits &#40;microtophi&#41; and that 25&#37; of these patients showed ultrasound signs of inflammation<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; case of asymptomatic hyperuricemia&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Subsequently&#44; 3 additional studies in patients with prolonged asymptomatic hyperuricemia &#40;&#8805;2 years&#41; confirmed that 34&#8211;42&#37; of the patients had MSU deposits and 24&#37; had inflammation in the Doppler study&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">26&#8211;28</span></a> Lastly&#44; a recent study observed that the ultrasound presence of MSU deposits in patients with asymptomatic hyperuricemia was associated with an increased degree of coronary calcification&#46; The authors indicated that this finding was due to the inflammation mediated by the MSU crystal deposits&#44; a plausible but still unconfirmed explanation&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">These observations raise 2 important questions&#58; &#40;1&#41; if a patient with &#8220;asymptomatic hyperuricemia&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; A&#41; has tophi in the imaging techniques&#44; should they be considered a patient with asymptomatic gout &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; B&#41;&#63; and &#40;2&#41; if a patient with hyperuricemia and asymptomatic tophi has ultrasound signs of inflammation &#40;Doppler&#41;&#44; should they be treated with hypouricemic drugs&#63;</p><p id="par0050" class="elsevierStylePara elsevierViewall">If the answer to both questions is yes&#44; then we are faced with a large paradigm shift&#58; conducting joint ultrasonography would be appropriate for all patients with long-standing asymptomatic hyperuricemia&#44; as in the case referred to in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The findings and treatment could well change the clinical course of &#8220;asymptomatic hyperuricemia&#8221;&#44; which would completely diverge from the course currently advocated by the European and American guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">21&#8211;24</span></a> In this respect&#44; we should emphasize that the therapeutic indication approved by the European Medicines Agency for febuxostat &#40;the second marketed inhibitor of the enzyme xanthine oxidase&#44; after allopurinol&#41; is literally&#58; &#8220;<span class="elsevierStyleItalic">treatment of the chronic hyperuricemia in conditions of urate deposits&#46;&#8221;</span> This approach would enable starting hypouricemic treatment regardless of finding acute gout attacks&#46; Taking this measure&#44; however&#44; requires clinical trials that show its benefit&#46; The management of the necessary resources for conducting joint ultrasonography of all patients with relevant hyperuricemia &#40;&#8805;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; over an extended period of time &#40;e&#46;g&#46; &#8805;2 years&#41; is acceptable&#44; given that an abbreviated version of this examination can be performed in less than 10<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> Nevertheless&#44; prospective studies need to be conducted to answer these questions&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Gout&#58; tophaceous or nontophaceous&#63;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Clinicians know that disease manifestations depend&#44; in considerable measure&#44; to observer acumen and the availability of additional tests&#46; In a review of 14 studies&#44; approximately half of the patients with gout showed tophi when examined with ultrasonography&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> Therefore&#44; the clinical diagnosis of &#8220;nontophaceous gout&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; C&#41; is currently questionable if ultrasonography is not performed&#46; What would be the result of performing ultrasound examinations of knees and metatarsophalangeal joints for all patients with gout&#63; Two apparent benefits of this approach are that &#40;1&#41; it would modify the classification &#40;a patient with nontophaceous gout would be reclassified into the tophaceous gout group &#91;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; C would move to D&#93;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; case report of gout&#41; and &#40;2&#41; the hypouricemic treatment of patients with urate deposits would change in 2 ways&#46; First&#44; we would ensure a uricemic level below 5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL to achieve complete reabsorption of the tophi as soon as possible&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> Even at 2 years from the start of hypouricemic treatment&#44; numerous patients with gout have tophi and signs of inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> Second&#44; the finding of tophi and signs of inflammation requires that appropriate prophylaxis be added to the hypouricemic treatment to prevent acute inflammation attacks&#44; presumably triggered by the reabsorption of urate crystals&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> When tophi are detected&#44; the ultrasound follow-up helps determine its progression and establish the intensity of the hypouricemic treatment&#44; the most advisable uricemia concentrations and whether it is appropriate to maintain a prophylactic treatment while there are tophi&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> The current availability of ultrasonography leads us to the prediction that in the near future we will have the necessary studies to verify its potential apparent benefits resulting from its systematic use&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">One final thought&#58; imaging techniques can help provide a better clinical classification of asymptomatic hyperuricemia and gout and perhaps a more rational treatment&#46; However&#44; it will never substitute good clinical judgment and individualized treatment&#46; This is what constitutes the art of medicine&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study was the result of the research project &#8220;The internist&#39;s ultrasound&#8221; &#40;<span class="elsevierStyleItalic">La ecograf&#237;a del internista</span>&#41;&#44; Biomedical Research Foundation of University Hospital La Paz&#44; FIBHULP&#44; PI 1471&#44; and was made possible thanks to FIS &#40;15&#47;01000&#41; and the Mutua Madrile&#241;a&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The Metabolic-Vascular Unit of University Hospital La Paz is developing an educational program based on the practical teaching of clinical ultrasonography to medical internists and is being funded by Menarini Laboratories&#46;</p></span></span>"
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          "titulo" => "Clinical stages of hyperuricemia and gout"
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          "titulo" => "Asymptomatic hyperuricemia&#58; a benign entity&#63;"
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          "titulo" => "Gout&#58; tophaceous or nontophaceous&#63;"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The increase in serum urate concentrations &#40;hyperuricemia&#44; &#8805;7&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; creates crystals&#44; which promote inflammation and joint lesions&#46; Ultrasonography can reveal these urate deposits&#46; The presence of crystals suggests that a patient with hyperuricemia is actually experiencing asymptomatic gout&#44; and that a patient with gout without subcutaneous tophi could experience tophaceous gout&#46; The information offered by ultrasound &#40;double contour sign and hyperechoic concretions mimicking clouds&#41; enables a more specific classification of hyperuricemia and gout&#46; Additionally&#44; this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricemia and gout&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El aumento de la concentraci&#243;n s&#233;rica de uratos &#40;hiperuricemia&#44; mayor o igual a 7&#44;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; ocasiona cristales que promueven inflamaci&#243;n y lesi&#243;n articular&#46; La ecograf&#237;a puede poner de manifiesto estos dep&#243;sitos de urato&#46; Su presencia obliga a considerar que un paciente con hiperuricemia en realidad padece gota asintom&#225;tica&#44; y que un enfermo con gota sin tofos subcut&#225;neos puede tener gota tof&#225;cea&#46; La informaci&#243;n que ofrece la ecograf&#237;a &#40;signo del &#171;doble contorno&#187; y de concreciones hiperecog&#233;nicas simulando nubes&#41; posibilita una clasificaci&#243;n de la hiperuricemia y de la gota m&#225;s precisas&#46; Adem&#225;s&#44; esta informaci&#243;n puede dar lugar a modificaciones relevantes en cuanto al proceder diagn&#243;stico y terap&#233;utico en los enfermos con hiperuricemia y gota&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garc&#237;a Puig J&#44; Beltr&#225;n L&#44; Mej&#237;a Chew C&#44; Torres R&#44; Tebar M&#225;rquez D&#44; Pose Reino A&#46; La ecograf&#237;a en el diagn&#243;stico de la hiperuricemia asintom&#225;tica y la gota&#46; Rev Clin Esp&#46; 2016&#59;216&#58;445&#8211;450&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Main ultrasound findings indicative of monosodium urate deposits &#40;MUS&#41; in the patients referenced in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; &#40;A&#41; Obtaining an ultrasound longitudinal image of the femoral cartilage&#46; &#40;B&#41; Healthy patient&#59; the lower line corresponds to the cortical bone touching the hyaline cartilage&#46; The upper line corresponds to the surface of the hyaline cartilage exposed to the synovial liquid&#46; &#40;C&#41; Double contour sign in the patient with asymptomatic hyperuricemia described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The upper hyperechoic line is due to the MUS deposit on the hyaline cartilage&#46; &#40;D&#41; Ultrasound longitudinal image of the first metatarsophalangeal joint in the patient with gout&#44; apparently not tophaceous&#44; described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; &#40;E&#41; Irregular hyperechoic line &#40;arrows&#41; corresponding to the cortical bone&#46; A hyperechoic cloudy area &#40;line of points&#41; can be observed and is due to the MUS deposit &#40;tophus&#41;&#46; An anechoic surrounding halo &#40;points of arrows&#41; can be observed&#46; &#40;F&#41; Doppler signal &#40;&#8220;Christmas tree&#8221;&#41; suggestive of significant inflammatory response&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hyperuricemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#40;A&#41; Patients with increased serum urate concentrations&#44; with no ultrasound evidence of monosodium urate deposits &#40;e&#46;g&#46;&#44; heart failure and metabolic syndrome&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#40;B&#41; Patients with increased serum urate concentrations&#44; with ultrasound evidence of monosodium urate deposits &#40;e&#46;g&#46;&#44; the same patients as in A with &#8220;microtophi&#8221;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gout&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#40;C&#41; Patients who report an attack characteristic of gout&#44; with no ultrasound evidence of monosodium urate deposits&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#40;D&#41; Patients who report an attack characteristic of gout&#44; with ultrasound evidence of monosodium urate deposits &#40;&#8220;tophi&#8221; or &#8220;microtophi&#8221;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Asymptomatic hyperuricemia</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Case report&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Software engineer who consulted the doctor for obesity at 23 years of age &#40;103<span class="elsevierStyleHsp" style=""></span>kg&#44; height 180<span class="elsevierStyleHsp" style=""></span>cm&#41;&#46; The patient was diagnosed with nonautoimmune hypothyroidism and treated with replacement therapy until normal thyroid function was achieved&#46; Over the next 7 years&#44; the patient&#39;s urate levels ranged from 7&#46;7 to 12&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;mean of 21 readings&#44; 9&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#46; The patient had never had joint pain&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ultrasound findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The joint ultrasound of the knees revealed the &#8220;double contour sign&#8221; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The metatarsophalangeal joint of the right foot showed tophaceous deposits with a positive Doppler sign&#59; both are unequivocal signs of monosodium urate deposits &#40;tophi&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Considerations</td><td class="td" title="table-entry  " align="left" valign="top">Should the patient be diagnosed with &#8220;asymptomatic hyperuricemia&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; A&#41;&#44; or should the correct diagnosis be asymptomatic gout&#47;tophaceous gout &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; B or D&#41;&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Should we start hypouricemic treatment to reduce the urate deposits and inflammation&#44; considering the patient is only 31 years old and that life expectancy in our community is approximately 50 additional years&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">What is the therapeutic objective&#44; uricemia &#60;5 or &#60;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">How long should prophylaxis be maintained to prevent an acute gouty arthritis attack&#63; Until we achieve the established uricemia objective or until the urate deposits disappear in the follow-up ultrasound&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Gout</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Case report&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sixty-five-year-old mining engineer diagnosed with obesity&#44; isolated systolic arterial hypertension&#44; moderate left ventricular hypertrophy and microalbuminuria&#44; 2 lacunar strokes with no neurological sequela&#44; obstructive sleep apnea syndrome &#40;OSAS&#41; and metabolic syndrome &#40;normal HDL&#41;&#46; At 11<span class="elsevierStyleHsp" style=""></span>pm after an extended train trip&#44; the patient was awoken by acute pain in the big toe of the right foot&#44; which almost prevented ambulation&#46; The next day&#44; the patient was transferred to a healthcare center where inflammatory signs were observed in the distal interphalangeal joint&#44; as well as uricemia of 6&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; No clinical subcutaneous tophi were detected&#46; The inflammation improved with treatment in 24<span class="elsevierStyleHsp" style=""></span>h&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ultrasound findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The interphalangeal joint ultrasound of the big toe of the foot right showed a heterogeneous nodular image&#44; with hyperechoic areas and underlying bone erosions with peripheral Doppler uptake &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Considerations</td><td class="td" title="table-entry  " align="left" valign="top">Should the patient be diagnosed with &#8220;nontophaceous gout&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; C&#41;&#44; based on the classical criteria for establishing the diagnosis of gout&#44; with the &#8220;prefix&#8221; nontophaceous because tophi have not been found during the physical examination&#44; or should the correct diagnosis in this case be &#8220;tophaceous gout&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; D&#41;&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">What is the therapeutic objective&#44; uricemia &#60;5 or &#60;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">How long should prophylaxis be maintained to prevent an acute gouty arthritis attack&#63; Until we achieve the established uricemia objective or until the urate deposits disappear in the follow-up ultrasound&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Two cases studies to illustrate how ultrasound can modify the diagnosis and treatment of asymptomatic hyperuricemia and gout&#46;</p>"
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