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González-Gay" "autores" => array:2 [ 0 => array:3 [ "nombre" => "Diana" "apellidos" => "Prieto-Peña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Miguel A." "apellidos" => "González-Gay" "email" => array:1 [ 0 => "miguelaggay@hotmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Grupo de Investigación en Epidemiología Genética y Arterioesclerosis de las Enfermedades Sistémicas y en Enfermedades Metabólicas Óseas del Aparato Locomotor, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Facultad de Medicina, Universidad de Cantabria, Santander, Cantabria, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Investigación en Genética y Fisiopatología Cardiovascular, Facultad de Fisiología y Ciencias de la Salud, Universidad de Witwatersrand, Johannesburg, South Africa" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico de la arteritis de células gigantes" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Giant cell arteritis (GCA) is the most common type of vasculitis among patients over the age of 50 living in Western countries. It is classically described as a vasculitis with particular tropism for the cranial arteries and whose most recognizable manifestations are headache, jaw claudication, and visual symptoms, which, in the most severe cases, can progress to complete blindness.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Because of the above, for many years it was referred to as temporal arteritis.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However, the most recent lines of research indicate that GCA is a more heterogeneous disease than previously thought. The emergence of new imaging techniques has allowed for identifying the involvement of extracranial vessels in patients with GCA. In this regard, it is now believed that GCA can present with two patterns that often overlap: cranial and extracranial.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Over the past decades, the criteria<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> proposed by the American College of Rheumatology (ACR) in 1990 for GCA have proven useful for identifying patients presenting with predominantly cranial clinical manifestations. These criteria include: (1) age greater than or equal to 50 years at symptom onset, (2) headache of recent onset or different from a pre-existing headache, (3) changes in the appearance of the temporal arteries, (4) erythrocyte sedimentation rate greater than or equal to 50 mm/h, and (5) temporal artery biopsy revealing vasculitis with a predominantly mononuclear inflammatory infiltrate and granuloma formation. The presence of at least three of these criteria enables a diagnosis of GCA to be established with a sensitivity of 93% and a specificity of 91.2%.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, the 1990 ACR criteria do not allow for diagnosing patients with GCA with predominantly extracranial manifestations at onset.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In contrast to patients with the classic predominantly cranial presentation, patients with isolated extracranial GCA are often younger and begin manifesting nonspecific clinical manifestations, often in the absence of the classic cranial symptoms. In these patients, the predominant clinical presentation is often a girdle syndrome that usually presents at an earlier age and can be associated with constitutional symptoms, such as fever, asthenia, and weight loss, as well as atypical symptoms such as inflammatory lower back pain or claudication of the upper and lower limbs.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> In general terms, the increase in acute phase reactant levels is usually less significant in patients with extracranial GCA. The findings of several studies have shown that these patients have a lower risk of developing cranial ischemic complications. However, their symptoms are often more refractory to glucocorticoid therapy and their risk of relapse is higher.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> In contrast to patients with the classical form, in patients with a predominantly extracranial phenotype of GCA, a temporal artery biopsy is usually negative, which consequently hinders and delays the diagnosis and can lead to serious complications such as the onset of aneurysms, stenosis, and aortic dissection.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Imaging tests, including ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are essential for reaching the diagnosis of extracranial GCA.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It has been noted above that the diagnosis of GCA remains eminently clinical. In the presence of a patient over the age of 50–60 years presenting with typical cranial manifestations and elevated acute phase reactant levels in a laboratory analysis, confirmatory diagnostic testing, either a biopsy or an ultrasound of the temporal arteries, should be performed.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Temporal artery biopsy continues to be the gold standard test for confirming the diagnosis of GCA, with a sensitivity of up to 40% and a specificity of 100%. The yield of temporal artery biopsy increases when performed during the first two weeks of starting glucocorticoid therapy. The length of the biopsy should be at least 0.5 cm, although it is advisable to obtain a sample measuring 1−2 cm in length.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Characteristic histological findings include transmural inflammatory infiltrate predominantly comprising macrophages and CD4-positive lymphocytes, with giant cells being present in up to 50% of positive biopsies.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Other characteristic findings are fragmentation of the internal elastic lamina, hyperplasia of the tunica intima, and generation of new capillaries.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The latest recommendations of the European League Against Rheumatism (EULAR) for the imaging of GCA includes ultrasound of the temporal arteries as an alternative test to confirm the diagnosis of GCA.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Ultrasound of the temporal arteries is a non-invasive and easily accessible technique that has proven useful for the diagnosis of GCA, with a sensitivity of 54%–91% and a specificity of 81%–95.8%, as reported in different studies.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> To perform an ultrasound, high-frequency linear probes of at least 15−18 MHz and a Doppler color mode are required. To correctly evaluate the temporal arteries, a transversal and longitudinal bilateral examination of the three branches of the temporal artery (i.e., common trunk, parietal branch, and frontal branch) is recommended. An ultrasound allows for viewing the “halo sign”, a homogeneous and hypoechoic thickening of the vascular wall indicative of an inflammatory process. Persistence of this halo sign in a “compression test”, whereby pressure is exerted on the examined vascular territory with the ultrasound probe, is highly indicative of vasculitis and aids in distinguishing thickening of the vascular wall caused by vasculitis from that caused by other processes, such as atherosclerotic disease. The Outcome Measures in Rheumatology (OMERACT) working group, which is composed of both European and American experts, has recently published a series of indications with the aim of standardizing and validating the definitions of ultrasonographic findings in patients with GCA.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In routine clinical practice, the interpretation of the ultrasound images of the temporal arteries are described as presenting a positive or negative halo. However, with a view to increase the precision and reliability of ultrasonography for the diagnosis of GCA, several expert groups are working to establish cut-off points for the measurement of the intima-media thickness (IMT) of the vascular wall. In this sense, the cutoff points that are currently being used are an IMT of 0.42 mm, 0.29 mm, and 0.34 mm for the common trunk, the parietal branch, and the frontal branch, respectively. Examining the axillary arteries to rule out extracranial involvement is also advised, considering an IMT ≥ 1 mm as a cut-off point.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Studies carried out by Miguel et al. recommend including a systematized examination of the carotid arteries to avoid interpretation errors, as the presence of atherosclerosis with a carotid IMT > 0.9 mm has been correlated with false positives when interpreting temporal artery ultrasound findings.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> According to the EULAR recommendations for the diagnostic imaging of GCA, in the case of a high clinical suspicion confirmed by ultrasound findings, performing additional diagnostic tests would not be necessary.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In questionable cases, the use of high-resolution 3 T magnetic resonance imaging (MRI) of the cranial arteries has been proposed.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The main advantage of this technique is that a single, noninvasive test enables the study of all cranial arteries.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> However, the availability of this test is often limited considering its high costs and demand for the diagnosis of other diseases. In addition, its use is limited in patients with pacemakers or metal prostheses, chronic kidney disease, or claustrophobia. Because of this, ultrasonography remains the imaging technique of choice for the diagnosis of patients with GCA of the cranial phenotype.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients with extracranially predominant GCA represent a diagnostic challenge. In some cases, an imaging test reveals the existence of asymptomatic large vessel vasculitis. The most typical example of this is the detection of large vessel vasculitis clinically presenting as isolated polymyalgia rheumatica in some patients.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The imaging techniques recommended by the latest EULAR guidelines for the diagnosis of extracranial GCA include ultrasonography, MRA, CTA, and 18-FDG PET/CT.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> As corroborated by the EULAR guidelines, which we fully support based on our own experience, the ideal is to use the diagnostic test with which each particular hospital is most familiar and which is most accessible in each site, always seeking to use the one offering the greatest diagnostic yield.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Ultrasonography enables the examination of the most superficial branches of the aorta, such as the axillary and subclavian arteries. This technique is useful for the early and non-invasive detection of the existence of extracranial involvement in patients with GCA. However, its usefulness is limited when evaluating deeper vessels, such as the thoracic and abdominal aorta. Thus, in cases of high clinical suspicion, other imaging tests are required to fully rule out this condition.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Both MRA, CTA, and 18-FDG PET/CT have demonstrated a high sensitivity and specificity for the diagnosis of large vessel vasculitis and also allow to rule out structural vascular damage, such as stenosis, occlusions, and aneurysms.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> Compared with ultrasound, these imaging tests offer a global image of the extension and severity of the large vessel involvement. The decision to use one or another imaging test will depend on their availability and the experience of each site, which should choose the most appropriate one according to the comorbidities of each particular patient.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Considering the results of a study carried out by our research group, the use of 18-FDG PET/CT may prove particularly useful for the diagnosis of extracranial GCA in patients with refractory polymyalgia with atypical manifestations, such as predominant involvement of the pelvic girdle, presence of inflammatory lower back pain, and claudication of the lower limbs.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In addition, from our point of view, this imaging technique offers the advantage of ruling out other diseases that can also present with girdle and constitutional syndrome, such as neoplasms or other systemic inflammatory diseases, during the same examination, as the presence of entities that mimic polymyalgia rheumatica is not exceptional.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Several expert groups are joining efforts to attempt to standardize and validate the acquisition and interpretation of 18-FDG PET/CT images in large vessel vasculitis.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In this regard, the most common interpretation method in clinical practice is the use of a visual scale of vascular 18-FDG uptake compared with the uptake of this radiopharmaceutical in the liver. Semiquantitative measurement methods that allow for increasing precision have been proposed for research purposes.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Although more diagnostic tools are now available, the diagnosis of GCA continues to entail a challenge in clinical practice in many cases, particularly in patients with predominantly extracranial manifestations in whom the 1990 ACR criteria do not facilitate establishing a diagnosis. Close collaboration and consensus between the different physicians attending these patients are fundamental goals to be achieved. In this sense, it is essential to establish multidisciplinary units, as well as rapid access and diagnosis consultations for GCA, as these have proven to reduce severe complications caused by a delay in the diagnosis of this condition.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Ultimately, GCA is an entity that requires a prompt diagnosis and initiation of glucocorticoid therapy to avoid the onset of potentially severe complications. A high clinical suspicion, together with early referral to units specializing in the treatment of GCA, are the basis to guarantee a correct management of this disease. The classic diagnostic approach for cranial GCA continues to be based on the 1990 ACR criteria, including the conduct of a temporal artery biopsy.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, according to recognized expert groups and the latest EULAR recommendations for the diagnosis of GCA, the presence of a halo sign in ultrasonographic images of the temporal arteries of patients in whom this entity is highly suspected is enough to establish the diagnosis of GCA without the need for further diagnostic testing.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The identification of patients with GCA with a predominantly extracranial phenotype is more complex given the non-specific nature of their symptoms. Thus, in these case it is essential to use imaging techniques such as ultrasonography, MRA, CTA, or PET/CT to establish the diagnosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">Diana Prieto-Peña is a beneficiary of a Río Hortega Contract from the Carlos III Health Institute (<span class="elsevierStyleItalic">Instituto de Salud Carlos III</span>) (ref. CM20/00006) and has received research fees/grants from <span class="elsevierStyleGrantSponsor" id="gs0005">UCB,</span><span class="elsevierStyleGrantSponsor" id="gs0010">Roche,</span><span class="elsevierStyleGrantSponsor" id="gs0015">Sanofi,</span><span class="elsevierStyleGrantSponsor" id="gs0020">Pfizer,</span><span class="elsevierStyleGrantSponsor" id="gs0025">Abbvie,</span><span class="elsevierStyleGrantSponsor" id="gs0030">Lilly, and the S</span><span class="elsevierStyleGrantSponsor" id="gs0035">panish Rheumatology Foundation</span>(<span class="elsevierStyleItalic">Fundación Española de Reumatología</span>) in the context of the FER-GALAPAGOS Program.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Miguel A. González-Gay has received research fees/grants from Abbvie, <span class="elsevierStyleGrantSponsor" id="gs0040">MSD,</span><span class="elsevierStyleGrantSponsor" id="gs0045">Janssen,</span> Roche, Pfizer, Sanofi, Lilly, <span class="elsevierStyleGrantSponsor" id="gs0050">Celgene, and</span><span class="elsevierStyleGrantSponsor" id="gs0055">Sobi.</span></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Prieto-Peña D, González-Gay MA. El diagnóstico de la arteritis de células gigantes. Med Clin (Barc). 2021;157:285–287.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of giant cell arteritis and polymyalgia rheumatica" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Gonzalez-Gay" 1 => "T.R. Vazquez-Rodriguez" 2 => "M.J. Lopez-Diaz" 3 => "J.A. Miranda-Filloy" 4 => "C. Gonzalez-Juanatey" 5 => "J. 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Journal Information
Vol. 157. Issue 6.
Pages 285-287 (September 2021)
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Vol. 157. Issue 6.
Pages 285-287 (September 2021)
Editorial article
Giant cell arteritis diagnosis
Diagnóstico de la arteritis de células gigantes
a Servicio de Reumatología, Grupo de Investigación en Epidemiología Genética y Arterioesclerosis de las Enfermedades Sistémicas y en Enfermedades Metabólicas Óseas del Aparato Locomotor, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
b Facultad de Medicina, Universidad de Cantabria, Santander, Cantabria, Spain
c Unidad de Investigación en Genética y Fisiopatología Cardiovascular, Facultad de Fisiología y Ciencias de la Salud, Universidad de Witwatersrand, Johannesburg, South Africa
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