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"micodemas@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Esmeralda" "apellidos" => "Núñez Cuadros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Rocío" "apellidos" => "Galindo Zavala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Leticia" "apellidos" => "Núñez Caro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Gisela" "apellidos" => "Díaz-Cordobés Rego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Antonio" "apellidos" => "Urda Cardona" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "UGC Pediatría, Hospital Materno-Infantil de Málaga, Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Reumatología Pediátrica, Hospital Materno-Infantil de Málaga, Málaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "UGC Reumatología, Hospital Regional Universitario de Málaga, Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Osteomielitis multifocal recurrente en niños: experiencia de un centro de tercer nivel" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction and Objectives</span><p id="par0005" class="elsevierStylePara elsevierViewall">Non-bacterial chronic osteomyelitis (NBCO) is a condition which is characterised by the existence of aseptic bone inflammation. There are different types of this disease with chronic recurrent multifocal osteomyelitis (CROM) being the most serious.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">CROM is now considered to be a polygenic autoinflammatory disease. It is characterised by the presence of several inflammatory osseous foci (or one associated with acne conglobata) which persists for over 6 months, with the course of the disease alternating between exacerbations and periods of remission.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,3,4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The main symptom is pain, usually inflammatory, and may become severely disabling. It may also be associated with general symptoms such as low-grade fever or asthenia. Although it may present in the form of a single focal point, multifocal and symmetrical presentation is more common in most cases,<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,5–8</span></a> generally affecting children with a mean age of 8.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,4</span></a> Its most typical location is the metaphysis of long bones and it most frequently affects the femur, the tibia, the vertebrae, the pelvic bones and the clavicle,with a mean of 4 foci.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,2,5,6,9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A diagnosis of exclusion is made and particularly in the single focus forms of the disease, where it is necessary to rule out tumour pathology and bacterial infection.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> For this it may be necessary to order a bone biopsy, although criteria for this referral is not currently well defined. However, it may be associated with autoimmune diseases including inflammatory intestinal disease, or it may form part of syndromic conditions such as the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteomyelitis).<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4,10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Non steroid anti-inflammatory drugs (NSAIDS), systemic corticoids, and biologics may be used as treatment but there are no well-defined guidelines or protocol for their use.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11–13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In general, it is not a well-known disease due to its recent description<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,10</span></a> and it is therefore underdiagnosed. It is thus important to be familiar with its clinical characteristics and the findings of the additional tests to obtain an early diagnosis. Furthermore there is no protocol or consensus regarding diagnosis and standardised treatment on an international level which would facilitate the approach to this pathology.</p><p id="par0035" class="elsevierStylePara elsevierViewall">For all of the above, the main aim of our study was to analyse the clinical, diagnostic-therapeutic and developmental features of the patients with this pathology in follow-up in our centre.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">Retrospective descriptive study of patients under 14 years of age who had been diagnosed with NBCO between 2010 and 2015 in a tertiary level hospital.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Patients diagnosed with CROM in keeping with Jansson's criteria (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) were included and all those who did not meet with these criteria were excluded.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Remission was considered to be the absence of activity for over 6 months and in a well controlled disease the absence of symptoms and relapses.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Relapse was considered to be the reappearance of symptoms after a period of absence of the same symptoms for over a month.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In our centre a protocol of procedure has existed since the year 2010 for all patients on wards or in consultation in paediatric rheumatology department with criteria compatible with NBCO. This protocol consists of: initial screening with acute phase reactants, serologies,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> the Mantoux test and plain radiography of the painful area.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,3,6–8,15</span></a> Once clinical suspicion has been established, in all cases bone scintigraphy was performed with Tc99 for determining the number of inflammatory foci. However, magnetic resonance was used to define the type of lesions detected, as recommended in the literature.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,16</span></a> Afterwards, after a meeting with the multidisciplinary committee, the need for bone biopsy was discussed. Regarding treatment, NSAIDS were used in addition to systemic corticoids, methotexate, pamidronate and anti-TNF in scaled format in accordance with <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">After 5 years of experience and the hypothesis that the protocol is useful for diagnosis and disease approach a retrospective review was made of the clinical files of these patients in accordance with the regulations stipulated by the ethics committee of our centre for this end.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The study was not reviewed by an ethics committee although it did comply with the main ethics for data treatment proceeding from the biomedical research with human beings (Geneva 2002).</p><p id="par0075" class="elsevierStylePara elsevierViewall">A descriptive study was conducted of the following variables: gender, age, location, number of foci, symptoms and duration of symptoms, time of evolution until diagnosis, lab results and imaging test results, findings from biopsy, treatment received and duration, number of relapses or recurrences. The results were expressed as percentages in the qualitative variables, as mean and standard deviation in those quantitative variables which followed a normal distribution and as median, interquartile range or range between maximums and minimums in those where it did not. Adjustment to normality of the quantitative variables was measured by the using the Shapiro–Wilk test. Statistical analysis was made with the help of the SPSS v22 package (University of Malaga licence).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Patient characteristics are listed in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. In sum, 12 cases were diagnosed, with a mean age of 11 years (±1.6 SD) and female:male ratio was 10:2. It is worth highlighting that 60% of patients were initially diagnosed with infectious osteomyelitis, with diagnosis being reformulated due to persistence of pain, poor radiologic and analytical evolution, and/or the appearance of new foci of osteomyelitis, despite wide spectrum antibiotic treatment.</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Although 16.7% presented with a single focus, the mean number of foci was 3.5 (±2.2 SD). The most common locations were the clavicle and ankle (tibia, fibula and astraglus). All consulted for pain. 75% suffered from associated functional impotence and 58% from fever. One case had associated acne conglobata and another an intestinal inflammatory disease, the main symptom of which was abdominal pain. Regarding lab test changes only a slight rise in CRP was noted (median: 18.1<span class="elsevierStyleHsp" style=""></span>mg/l; range: 3.8–235) and ESR (mean: 53.4<span class="elsevierStyleHsp" style=""></span>mm/h<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>35.2 SD) in 72% and 63.6% of cases, respectively. In all cases magnetic resonance imaging was performed with the most common finding being medullary oedema and with lytic lesion appearing in 50%. Biopsy was performed in 60% of patients, observing in all of them chronic inflammation and fibrosis. All the patients received NSAIDS, with 50% of them requiring prednisone due to the persistence of clinical symptoms after 4 weeks. 33% of patients required a third therapeutic scale (methotrexate/pamidronate) from relapses after withdrawal from corticotherapy. The case associated with intestinal inflammatory disease and the case associated with acne conglobata were treated with subcutaneous adalimumab, with excellent clinical response. Up until now, no serious secondary effects have been recorded in our patients.</p><p id="par0090" class="elsevierStylePara elsevierViewall">All the cases with diagnostic delay of above 5 months received maintenance treatment with paramidronate or methotrexate, whilst only 16% of patients with early diagnosis required it.</p><p id="par0095" class="elsevierStylePara elsevierViewall">No patient presented with serious sequelae. Only one physeal fusion bridge at right ankle level was detected in one case, without any limitation of associated movement. At present only 16% of patients require treatment for control of symptoms, and these are the patients who require biologics. For those who require pamidronate the treatment may be withdrawn after symptom control (mean 5 months of treatment). In the case of methotrexate treatment was withdrawn after a year of disease inactivity. However, recurrences presented in 66% of cases, and up to on 5 occasions in one. The appearance of a non-Hodgkin lymphoma after 2 years from the CROM diagnosis was notable, when the patient was in remission without treatment.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion and Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">As recorded in our study, non-bacterial osteomyelitis (NO) is a pathology which presents in childhood with pain, swelling, functional limitation and impotence and the disease course results in outbreaks, with patients being asymptomatic when not suffering from them. It may be associated with general symptoms of asthenia, fever or weight loss, with a median of 4 outbreaks annually.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,5,6,9,17–19</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">There is a strong association with autoinflammatory and autoimmune diseases, and in particular with psoriasis, in those subjects affected and their direct family members, which suggests a common psychopathology and supports the idea of a genetic susceptibility component.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,20,21</span></a> In our sample there were 2 cases of associated pathology, including acne conglobata and intestinal inflammatory disease. Both of these had previously been described in the literature. Furthermore, it may form part of the syndromic characteristics such as the SAPHO syndrome, that of Majeed (neutrophilic dermatosis, anaemia, fever, arthralgias and osteomyelitis) and insufficient IL1 receptor antagonist or DIRA (respiratory distress, pustulosis, oral mucous lesions, arthritis and multifocal osteomyelitisl).<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4,10</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">One of the most controversial points is the diagnostic method to be followed. In our case we applied the diagnostic criteria of Jansson (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2,4</span></a> for greater precision, but those of Handrick and Bristol<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> are also described in the literature and recently those of Roderick et al.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> There is thus a need for a combination of clinical, radiological and anatomopathological findings</p><p id="par0115" class="elsevierStylePara elsevierViewall">Once clinical suspicion has been established, and for the differential diagnosis with other pathologies which may present with similar clinical symptoms, certain ancillary tests would be indicated.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5,14,21</span></a> In our sample we used analysis, radiography, scintigraphy and/or magnetic resonance.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15,16</span></a> Bone scintigraphy with c99 is particularly useful in this pathology since active foci often exist which are not symptomatic and this technique has high sensitivity (around 90%) for their detection.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> However, given its low specificity (around 75%),<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> the literature recommends magnetic resonance to better define detected lesions.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,16</span></a> In different publications, total corporal magnetic resonance is considered as an alternative but this is not available in all centres for children due to the length of the procedure and its high cost.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Moreover, in the case of lesions under 6-month duration, which are unifocal with an infiltrated or osteolitic infiltrate appearance, it is recommended that a biopsy be carried out.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5,13,15</span></a> In our sample this was obtained in 9 patients, due to the short evolution and radiologic findings in the majority of cases.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding therapeutic management the NSAIDS are first line treatment. However, they are only useful for symptom relief, without having any effect on the radiologic image.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,12,22,23</span></a> For this reason, all of our patients were initially treated with NSAIDS (usually naproxen), essentially during the diagnostic process.</p><p id="par0130" class="elsevierStylePara elsevierViewall">If clinical symptoms persisted despite treatment with NSAIDS, treatment with systemic corticoids may be considered for no more than 4–6 weeks. If subsequent to this discontinuity is not possible, biphosphonates are prescribed, and specifically intravenous pamidronate, which has the greatest use from broad existing experience with this drug in paediatrics. In recent years the possibility of directly initiating treatment with pamidronate has been considered if symptoms cannot be controlled with NSAIDS since this would lead not just to fast relief of symptoms but possibly also disease remission. Furthermore, data on the safety of this treatment are increasingly more abundant, with the most frequent side effects in children being flu-like syndrome after the first infusion and electrolyte changes such as hypocalcaemia, hypophosphatemia or hypomagnesemia, all of which are usually asymptomatic.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13,16,24–27</span></a> Lastly, in refractory cases to pamidronate, anti-TNF inhibitors could be used as an alternative.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28–30</span></a> In our case this treatment guideline was followed, without any notable side effects being recorded (<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>).</p><p id="par0135" class="elsevierStylePara elsevierViewall">According to the literature, the prognosis of these patients is good, with disease duration between 2 and 20 years, and a mean of 4.5 years. It is completely resolved in 73% of cases, without sequelae or new outbreaks, and on occasion even spontaneously.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1–3,6–9</span></a> In our sample we were able to discontinue treatment in 10 patients (83.33%).</p><p id="par0140" class="elsevierStylePara elsevierViewall">On rare occasions there may be complications such as early physeal fusion and lack of growth, degenerative arthrosis, bone deformity and pathological fractures.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> In our sample, up until now only one case of a physeal bone bridge has occurred.</p><p id="par0145" class="elsevierStylePara elsevierViewall">According to our results, delayed diagnosis and the existence of associated pathology could involve a higher need for scaled therapy and further recurrences. This fact is compatible with what has been published in the literature, since it defends that early diagnosis is related to a more benign course of the disease and the presence of comorbidity with the need for a more intensive treatment.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18,27–30</span></a> Furthermore, Catalano et al. relates persistent disease with a number of foci,<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> a fact which is not correlated with our findings.</p><p id="par0150" class="elsevierStylePara elsevierViewall">To conclude, although the spectrum of this disorder is broad, we should suspect it when osteomyelitis is of torpid evolution or new foci appear despite appropriate antibiotic treatment. Biopsy should be reserved for cases of single focus, short evolution or which present data suggestive of malignancy in the ancillary tests performed. NSAIDS remain first line treatment although other alternatives exist, such as pamidronate or anti-TNF agents. We believe that despite sample size, the results obtained with pamidronate in our series allows us to conclude that it is an appropriate alternative when NSAIDS fail.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Delayed diagnosis may lead to higher exposure to diagnostic tests and a need for therapeutic scaling and from there the need for a high level of suspicion.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Recurrences may be related to time of evolution to diagnosis and with the existence of associated pathology. As a result, the establishment of diagnostic therapeutic protocols is needed to help professionals approach this pathology.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical Disclosure</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Protection of people and animals</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that for this research no experiments have been carried out on humans or animals.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Confidentiality of data</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have adhered to the protocols of their centre of work on the publication of patient data.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Right to privacy and informed consent</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of Interests</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1101213" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1042054" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1101214" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1042053" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction and Objectives" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion and Conclusions" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Disclosure" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of Interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-12-21" "fechaAceptado" => "2017-04-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1042054" "palabras" => array:5 [ 0 => "Nonbacterial osteomyelitis" 1 => "Chronic recurrent multifocal osteomyelitis" 2 => "Children" 3 => "Pamidronate" 4 => "Tumour necrosis factor α inhibitor therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1042053" "palabras" => array:5 [ 0 => "Osteítis no bacteriana" 1 => "Osteomielitis multifocal crónica recurrente" 2 => "Niños" 3 => "Pamidronato" 4 => "Tratamiento antifactor de necrosis tumoral alfa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chronic recurrent multifocal osteomyelitis is a rare aseptic bone inflammation that affects paediatric patients. Its management and treatment have not yet been standardised.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective, descriptive study of patients under 14 years of age diagnosed with chronic nonbacterial osteomyelitis (CNBO) in a tertiary hospital. We included patients diagnosed over the last 6 years (2010–2015) who met the Jansson criteria. The clinical and radiological characteristics of CNBO were analysed, as was the outcome after different therapeutic options.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We report 12 patients, with a mean age of 11 years (±1.6 standard deviation [SD]) and female predominance (10:2). The mean number of foci was 3.5 (±2.2 SD). The most common locations were ankle (58%), clavicle (50%), sternum (33%) and hip (25%). The mean disease duration was 10.5 months (±10.3 SD), and the median time to diagnosis was 2.38 months (range 0.17–16). Bone scintigraphy detected asymptomatic foci in 33% and we detected lytic lesions in 50% through magnetic resonance imaging. Biopsy was performed in 60%; 2/12 (16%) were associated with inflammatory disease and 1/12 (8.3%) later developed lymphoma. In all, 58% received antibiotic therapy with little response, 100% anti-inflammatory agents, 50% systemic corticosteroids, 41.6% methotrexate/pamidronate and 16% anti-tumour necrosis factor (TNF) α. The mean duration of treatment was 14.8 months (±12.4 SD) and 66% had recurrences. Currently, 83% are in clinical remission without treatment.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">When CNBO is refractory to treatment with anti-inflammatory drugs, intravenous pamidronate can be an alternative. Anti-TNF drugs can be considered in patients who fail with pamidronate, as can agents associated with other autoimmune conditions.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La osteomielitis multifocal crónica recurrente es una inflamación ósea aséptica poco frecuente en pediatría cuyo abordaje y tratamiento no está estandarizado.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio descriptivo retrospectivo de menores de 14 años a quienes se diagnosticó osteomielitis crónica no bacteriana (OCNB) en un hospital de tercer nivel. Se incluyeron los pacientes diagnosticados en los últimos 6 años (2010-2015), y que cumplían los criterios de Jansson. Se analizaron las características clínicas y radiológicas, y su evolución tras las diferentes opciones terapéuticas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 12 casos, con 11 años de media (±1,6 desviaciones estándar [DE]), y predominio femenino (10:2). La media de focos fue de 3,5 (±2,2 DE). Las localizaciones más frecuentes fueron: tobillo (58%), clavícula (50%), esternón (33%) y cadera (25%). La media de tiempo de evolución fue de 10,5 meses (±10,3 DE) y la mediana hasta el diagnóstico de 2,38 meses (0,17-16). En el 33% se detectaron focos asintomáticos con gammagrafía ósea y en el 50% lesiones líticas con resonancia. Se realizó biopsia en el 60%; 2/12 (16%) asociaron patología inflamatoria y 1/12 (8,3%) desarrolló linfoma posteriormente. El 58% recibieron tratamiento antibiótico con escasa respuesta, el 100% antiinflamatorios, y el 50% corticoides sistémicos. El 41,6% requirieron metotrexato o pamidronato, y el 16% anti-TNFα. La media de tiempo de tratamiento fue de 14,8 meses (±12,4 DE), presentando recurrencias el 66%. Actualmente el 83% se encuentran en remisión clínica sin tratamiento.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En OCNB refractarias a antiinflamatorios, el pamidronato intravenoso podría constituir una alternativa terapéutica en niños. Los fármacos anti-TNFα podrían considerarse en pacientes con fracaso a pamidronato, o aquellos que asocien entidades autoinmunes.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Ariza Jiménez AB, Núñez Cuadros E, Galindo Zavala R, Núñez Caro L, Díaz-Cordobés Rego G, Urda Cardona A. Osteomielitis multifocal recurrente en niños: experiencia de un centro de tercer nivel. Reumatol Clin. 2018;14:334–338.</p>" ] ] "multimedia" => array:4 [ 0 => 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:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Diagnostic confirmation with two major criteria or one major and three minor criteria.</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">CROM: chronic recurrent multifocal osteomyelitis; ESR: erythrocyte sedimentation rate.</p>" "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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Major criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Minor criteria \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">Multifocal bone lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good general status \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">Osteolytic/sclerotic lesion in the radiography \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Course of disease over 6 months \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">Sterile biopsy with signs of inflammation/fibrosis or sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lab results normal and raised ESR \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">Palmoplantar psoriasis or pustulosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hyperostosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Association with autoimmune or autoinflammatory disease apart from psoriasis and pustulosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1884096.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Criteria of Jansson for Diagnosis of CROM.</p>" ] ] 1 => 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:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">NSAID: non-steroid anti-inflammatory drugs; CROM: chronic recurrent multifocal osteomyelitis.</p>" "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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1st NSAID<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ibuprofen/naproxen \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">2nd Systemic corticoids<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oral prednisone 1–2<span class="elsevierStyleHsp" style=""></span>mg/kg/day for 2 weeks with subsequent progressive reduction \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">3rd I.V. Pamidronate<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>mg/kg/dose (see <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>) \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">4th Biologics<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S.c. Adalimumab 24<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/14 days and/or s.c./o.r. methotrexate 10–15<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/weeks. Other options: infliximab, etanercept \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1884097.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Administered for the first month or whilst the study is completed.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">May be maintained for one month maximum. If new outbreaks occur or there are complications i.v. pamidronate will be administered. This is maintained until symptoms disappear.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">On occasions first option may be pamidronate without previous therapy with corticoids.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">This is prescribed when the disease is refractory to pamidronate or there is an associated autoimmune disease.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Treatment Protocol for Patient With CROM Used in Our Centre.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">NSAID: non steroid anti-inflammatory drugs; CROM: chronic recurrent multifocal osteomyelitis; QTc: corrected QT interval; PS: physiological saline.</p>" "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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Dose</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">1st Cycle</span>: \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1st day: .5<span class="elsevierStyleHsp" style=""></span>mg/kg \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2nd day: 1<span class="elsevierStyleHsp" style=""></span>mg/kg (maximum 60<span class="elsevierStyleHsp" style=""></span>mg) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3rd day: 1<span class="elsevierStyleHsp" style=""></span>mg/kg (maximum 60<span class="elsevierStyleHsp" style=""></span>mg) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Following cycles: 2 options</span>: \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mg/kg 1 dose per month \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mg/kg/day for 3 days every 3 months \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Maximum recommended dose: 11.5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg/kg/year</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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"><span class="elsevierStyleBold">Preparation</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dilute in 250–500</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ml of SSF</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Administer in 3–4</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pre-medicate with paracetamol (at least the first doses)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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"><span class="elsevierStyleBold">Most common side effects</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Flu-like syndrome and bone pain (may be treated with NSAIDS)</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hypocalcaemia and hypophospheremia. Treatment with calcium is recommended if symptoms or ionic calcium is <1</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mmol/l</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Vomiting and diarrhoea (try rehydration)</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Conjuntivitis (apply lavages with saline solution)</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Reversible cytopenias</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bone surgery after induction with pamidronate is not recommended. Contraindicated in severe kidney failure and enterocolitis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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"><span class="elsevierStyleBold">Follow-up</span> \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Extract haemogram, ions (including phosphorous), prescribe calcium/creatinine, vitamin D, baseline liver and kidney function, prior to treatment with pamidronate and after 2nd and 3rd dose.</span><br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">If calcium/creatinine prescribed >.2 a kidney scan should be performed to rule out nephrocalcinosis.</span><br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Administer calcium and vitamin D for maintenance in children with low calcium levels, or reduced vitamin D levels (with normal calcium/creatinine rates) or changes to QTc</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1884098.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Administration Protocol for Pamidronate in Paediatric Patients Diagnosed With CROM Used in Our Centre.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">NSAID: non-steroid anti-inflammatory drugs; SD: standard deviation; CROM: chronic recurrent multifocal osteomyelitis; RCP: reactive C-protein; IQR: interquartile range; MR: magnetic resonance; TNF: tumoral necrosis factor; ESR: erythrocyte sedimentation rate.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Patient characteristics (</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">12)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gender (female), n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (83.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age (years), mean</span> (±<span class="elsevierStyleItalic">SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Disease characteristics (</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">12)</span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Clinical symptoms, n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (100.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Functional impotence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (75.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (58.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Location of focis (n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">37), n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lower limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (51.4) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Clavicle \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (13.5) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ribs and/or sternum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (10.8) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hip \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (10.8) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Spine and/or sacrum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (8.1) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Upper limbs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (5.4) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Course of disease until first consultation (months), mean</span> (±<span class="elsevierStyleItalic">SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.5 (10.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Duration of symptoms until diagnosis (months) median (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.38 (4.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Results of ancillary tests (</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">12)</span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Analyses</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Leucocytes, mean (±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10,736 (±3905) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>CRP (mg/l), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.1 (48.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ESR (mm/h), mean (±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.4 (±35.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">MR, n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Oedema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (75.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cortical thickening \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (16.6) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lysis and/or cortical disruption \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (16.6) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Periostic reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (16.6) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Biopsy (n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">8), n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (62.5) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Inflammation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (50.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Necrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (25.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Treatments (</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">12),</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleBold">(%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antibiotic</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (58.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">NSAIDS</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (100.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Corticoids</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77 (58.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Methotrexate</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (8.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pamidronate</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (33.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Anti-TNFα</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1884099.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Epidemiological, Clinical and Diagnostic, Therapeutic Features of the Sample.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic nonbacterial osteomyelitis in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. 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Year/Month | Html | Total | |
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2024 October | 15 | 13 | 28 |
2024 September | 48 | 18 | 66 |
2024 August | 71 | 36 | 107 |
2024 July | 42 | 34 | 76 |
2024 June | 51 | 37 | 88 |
2024 May | 56 | 31 | 87 |
2024 April | 55 | 28 | 83 |
2024 March | 57 | 27 | 84 |
2024 February | 57 | 31 | 88 |
2024 January | 73 | 30 | 103 |
2023 December | 34 | 32 | 66 |
2023 November | 49 | 22 | 71 |
2023 October | 58 | 36 | 94 |
2023 September | 121 | 43 | 164 |
2023 August | 131 | 23 | 154 |
2023 July | 49 | 26 | 75 |
2023 June | 65 | 28 | 93 |
2023 May | 39 | 30 | 69 |
2023 April | 37 | 8 | 45 |
2023 March | 94 | 26 | 120 |
2023 February | 74 | 28 | 102 |
2023 January | 40 | 16 | 56 |
2022 December | 91 | 42 | 133 |
2022 November | 70 | 33 | 103 |
2022 October | 68 | 36 | 104 |
2022 September | 44 | 43 | 87 |
2022 August | 39 | 39 | 78 |
2022 July | 47 | 34 | 81 |
2022 June | 41 | 50 | 91 |
2022 May | 54 | 50 | 104 |
2022 April | 58 | 60 | 118 |
2022 March | 72 | 64 | 136 |
2022 February | 93 | 56 | 149 |
2022 January | 58 | 93 | 151 |
2021 December | 36 | 56 | 92 |
2021 November | 32 | 47 | 79 |
2021 October | 63 | 65 | 128 |
2021 September | 40 | 37 | 77 |
2021 August | 29 | 37 | 66 |
2021 July | 22 | 29 | 51 |
2021 June | 37 | 29 | 66 |
2021 May | 58 | 63 | 121 |
2021 April | 142 | 107 | 249 |
2021 March | 107 | 37 | 144 |
2021 February | 48 | 33 | 81 |
2021 January | 38 | 26 | 64 |
2020 December | 61 | 28 | 89 |
2020 November | 34 | 23 | 57 |
2020 October | 25 | 23 | 48 |
2020 September | 60 | 38 | 98 |
2020 August | 43 | 23 | 66 |
2020 July | 44 | 17 | 61 |
2020 June | 61 | 33 | 94 |
2020 May | 61 | 21 | 82 |
2020 April | 28 | 24 | 52 |
2020 March | 25 | 6 | 31 |
2019 June | 0 | 2 | 2 |
2019 April | 198 | 0 | 198 |