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Clinical perspective of anti-HMGCR immune-mediated necrotizing myopathy: analysis of three cases
Perspectiva clínica de las miopatías necrotizantes inmunomediadas anti-HMG-Co-A-reductasa: análisis de tres casos
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Quintana Cabezas, M.C. Yubini Lagos" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J.P." "apellidos" => "de la Fuente Peñaloza" "email" => array:2 [ 0 => "josepedro.delaf@gmail.com" 1 => "jdelafuente@hcuch.cl" ] "referencia" => array:3 [ 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">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Quintana Cabezas" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M.C." "apellidos" => "Yubini Lagos" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Medicina Norte, Facultad de Medicina, Universidad de Chile, Santiago, Chile" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección Medicina Interna, Hospital Clínico de la Universidad de Chile, Santiago, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Perspectiva clínica de las miopatías necrotizantes inmunomediadas anti-HMG-Co-A-reductasa: análisis de tres casos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Immune-mediated necrotizing myopathies (IMNM) are a relevant subgroup of idiopathic inflammatory myopathies (IIM) that account for approximately 10% of IIM. They are distinguished by a unique clinical, pathological, and serological presentation.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They cause severe muscle weakness and necrosis without significant inflammation on a muscle biopsy, differentiating them from other IIM such as polymyositis and dermatomyositis. The detection of specific antibodies such as anti-HMGCR and anti-SRP has allowed for a better classification of these conditions,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> leading in turn to an earlier and more accurate diagnosis,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> which is crucial for effective disease management.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This scientific letter presents an analysis of three cases of IMNM with positivity for anti-HMGCR autoantibodies seen at our university center, highlighting their distinctive features and the importance of an early diagnosis and individualized treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Description of cases</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 69-year-old woman with diabetes who had progressive symptoms that had been ongoing for four months of gait disturbance and symmetrical proximal weakness in the lower extremities that later affected the upper extremities and cervical musculature, accompanied by muscle pain. After detecting hypothyroidism and dyslipidemia, treatment with rosuvastatin, fenofibrate, and levothyroxine was initiated, which worsened the symptoms. A physical examination showed a 2-cm erythematous-violaceous indurated plaque in the right supraclavicular region, suggesting skin involvement. Elevated levels of transaminases, LDH, and total CK were observed, leading to discontinuation of lipid-lowering drugs and suspicion of IIM. Studies revealed positive anti-HMGCR antibodies and a biopsy of the plaque showed superficial and deep perivascular lymphoplasmacytic dermatitis, consistent with IMNM. Treatment with prednisone 60 mg/day was started. A partial response was observed, so methotrexate was added. Subsequently, the patient had clinical recurrence and was readmitted. After using methylprednisolone and intravenous immunoglobulins (IVIG), cyclophosphamide and cyclosporine were started, with progressive clinical improvement.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Case 2</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 47-year-old woman with diabetes who had myalgias and proximal weakness in upper and lower extremities that had been ongoing for eight months. A physical examination revealed M4 proximal strength with pain on muscle palpation. The initiation of rosuvastatin one month earlier coincided with symptoms onset. During her progress, a significant increase in total CK, LDH, and AST were observed, leading to suspicion of IIM. Studies showed positive anti-HMGCR antibodies and a muscle biopsy confirmed the diagnosis of IMNM. Steroid treatment with methotrexate was started. Three months later, the patient relapsed, presenting with M2 proximal strength and cephaloparesis. She was hospitalized and administered IVIG, methylprednisolone, and cyclophosphamide. Subsequently, she was transferred to her reference center and lost to follow-up.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case 3</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 78-year-old woman with hypertension, diabetes, and dyslipidemia with prolonged use of atorvastatin who had proximal muscle weakness in the four extremities and progressive dysphagia that had been ongoing for one year associated with an increase in total CK. Initially approached as polymyositis, treatment with prednisone and methotrexate was started and atorvastatin was suspended, with partial improvement. Four months later, she was diagnosed with breast cancer on the right side and received curative treatment. The patient had multiple complications, including thromboembolic disease and recurrent respiratory infections that led to loss to follow-up and discontinuation of methotrexate. Subsequently, she had a recurrence of the initial symptoms with respiratory failure and severe weakness. On readmission, she had M2 proximal strength in the lower extremities and M4 in the upper extremities. Studies revealed positive anti-HMGCR antibodies, confirming IMNM. Treatment with methotrexate and prednisone was restarted, achieving progressive clinical improvement and recovery of functionality.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The additional studies performed in these three patients, including CK levels, antibodies, MRI, and other clinical and laboratory findings are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Anti-HMGCR IMNM is clinically characterized by severe proximal muscle involvement which may extend to the pharyngeal and esophageal musculature.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Exposure to statins is an important risk factor<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> for its onset. Elevated CK and other markers of muscle injury are useful for both the diagnosis and monitoring of the disease.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Anti-HMGCR positivity is crucial for diagnosis,<span class="elsevierStyleSup">5</span> allowing histopathology to be avoided in most cases. EMG and MRI are complementary tools for evaluation of the disease, with roles in its differential diagnosis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Treatment of anti-HMGCR IMNM must be early and individualized. Induction therapy includes prednisone, methylprednisolone, and IVIG in severe cases<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> followed by methotrexate<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> or azathioprine.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In refractory cases, the use of rituximab,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> cyclophosphamide,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or plasmapheresis<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> can be considered. Anti-HMGCR IMNM has a less favorable prognosis compared to other IIM, with a notable need for early diagnosis and aggressive treatment.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> The combination of clinical and serologic features is fundamental for diagnosis, while MRI and EMG play a secondary role. Immunosuppressive therapy must be adjusted according to clinical response and the presence of complications.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interest statement</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Funding</span><p id="par0050" class="elsevierStylePara elsevierViewall">This research has not received specific grants from agencies in the public, commercial, or non-profit sectors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Description of cases" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Case 2" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Case 3" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest statement" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "xack786662" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 3 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total CK (NV < 135 U/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10,387 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10,622 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5669 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antinuclear antibodies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1/160 homogeneous nuclear (AC-1) and fine speckled (AC-4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mitotic pattern — mitotic spindle (AC-25) and intercellular bridge (AC-27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ENA (extractable nuclear antigen) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myositis-specific panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OJ (+) borderline, Ku (+) borderline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-HMGCR (NV: <20 U) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>200 U \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">181.7 U \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>200 U \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MRI myositis protocol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muscular, fascial, and subcutaneous plane edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muscular, fascial, and subcutaneous plane edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muscular, fascial, and subcutaneous edema. Mild-to-moderate diffuse fatty infiltration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EMG and NCV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute proximal myopathy (deltoid and iliopsoas) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N/P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proximal myopathy of 4 extremities and neck (shoulder and pelvic girdle) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muscle biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N/P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphohistocytic myositis with focal myonecrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated neoplasm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(–) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Breast cancer \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IVIG, cyclophosphamide + cyclosporine + corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IVIG + cyclophosphamide + corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methotrexate + corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3714343.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Characterization and treatment of patients with anti-HMGCR IMNM.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune-mediated necrotizing myopathy: clinical features and pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y. 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Werner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/kew470" "Revista" => array:6 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2017" "volumen" => "56" "paginaInicial" => "787" "paginaFinal" => "794" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28096458" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack786662" "titulo" => "Acknowledgments" "texto" => "<p id="par0055" class="elsevierStylePara elsevierViewall">We thank the immunology laboratory team for their support in the autoimmunity studies, the rheumatology team for their guidance in diagnosis and treatment, and the radiology team for their interpretation and analysis of the images.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000022400000009/v1_202411040629/S2254887424001140/v1_202411040629/en/main.assets" "Apartado" => array:4 [ "identificador" => "71813" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Correspondence" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000022400000009/v1_202411040629/S2254887424001140/v1_202411040629/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887424001140?idApp=WRCEE" ]
