Case Report
Chronic Eosinophilic Pneumonia: Autoimmune Phenomenon or Immunoallergic Disease? Case Report and Literature Review
Neumonía eosinofílica crónica; ¿fenómeno autoinmune o enfermedad inmunoalérgica? Reporte de un caso y revisión de literatura
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"apellidos" => "Meléndez-Mercado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Pablo" "apellidos" => "Aranda-Pereira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "División de Medicina Interna, Servicio de Reumatología, Centro Médico ISSEMYM, Toluca, Mexico" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Reumatología, Centro Médico ISSEMYM, Toluca, Estado de México, Mexico" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonía eosinofílica crónica; ¿fenómeno autoinmune o enfermedad inmunoalérgica? Reporte de un caso y revisión de literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 584 "Ancho" => 853 "Tamanyo" => 56052 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">High-resolution CT scan with lung window, which after 3 months of follow-up shows complete resolution of pneumonic inflammation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Eosinophilic pneumonias are a group of diseases extensively studied and described in the literature, which have been classified by their presentation in acute or chronic eosinophilic pneumonia (CEP), and the distinctive features of its presentation are based on the presence of cough, dyspnea, fever and pulmonary infiltrates due to the presence of inflammatory cell accumulation, with predominant eosinophils.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Acute eosinophilic pneumonia, as its name implies, has a sudden onset, usually associated with moderate to severe hypoxia, which may jeopardize the patients’ life,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> unlike CEP, is a benign form, with an insidious presentation with less respiratory impact.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In both cases, once the diagnosis is defined, there is a favorable response to glucocorticoids, the basis of its treatment, apparently based on an immunoallergic link underlying diseases such as allergic rhinitis, sinusitis, asthma and atopy.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The association of eosinophilia and rheumatologic diseases has been widely described in literature, and we can highlight as an example and mention some of them as eosinophilic fasciitis syndrome and Churg-Strauss,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> but there are other autoimmune diseases such as arthritis own (RA)<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and systemic lupus erythematosus, which described the presence of concomitant phenomena such as eosinophilic vasculitis, panniculitis, enteritis or eosinophillic pneumonia.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The pathophysiology of this association has not been well elucidated, as the eosinophil is a cell that has been very involved in the phenomena of autoinmunidad.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report a woman with symptoms of RA associated with clinical symptoms of chronic eosinophilic pneumonia, in which it is necessary to emphasize the production of autoantibodies and spontaneous remission.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Description of the Case</span><p id="par0020" class="elsevierStylePara elsevierViewall">The case was a 47-year-old woman, born in the State of Mexico. She had a history of being a smoker since age 16, with a consumption of 3–4 cigarettes a day until age 30 when she stopped. In 1999 she was treated for allergic rhinitis with antihistamines and nasal glucocorticoid drugs and, intermittently, parenteral glucocorticoids (every 6 or 8 months). The patient reported that her illness began early in 2008, with malaise, fever and the presence of joint pain. In later days dyspnea, fatigue and fever were added. She was seen by the family physician, who found the following laboratory results: positive rheumatoid factor (RF) 1:1.280 and eosinophilia of 15% (1605<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span>), for which she was referred to our hospital.</p><p id="par0025" class="elsevierStylePara elsevierViewall">On admission, the patient had rales in the upper third of both lungs, predominantly on the left hemithorax. The musculoskeletal examination showed no inflammatory data or functional limitation. The chest X-ray revealed bilateral pneumonia mainly on the left lung, and computed tomography data found a bilateral pneumonia mainly on the left lung (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). The sinus CT scan was normal. Pulmonary function tests were within normal limits, with an oxygen saturation of 95%.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">We began a study protocol for eosinophilia, and cytology confirmed eosinophils of 54.3% (4.487<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span>), with positive RF by nephelometry 204.5<span class="elsevierStyleHsp" style=""></span>IU/mL, and negative anti-citrullinated peptide antibodies 14.7<span class="elsevierStyleHsp" style=""></span>IU/mL (normal <25), elevated erythrocyte sedimentation rate 81<span class="elsevierStyleHsp" style=""></span>mm/h (Westergren), CRP 40.7<0.8<span class="elsevierStyleHsp" style=""></span>mg/dL, IgE 1596<span class="elsevierStyleHsp" style=""></span>IU/mL (normal <100), c-ANCA 1:80, 1:20 x-ANCA, with ELISA antibodies against proteinase-3 being 0.7<span class="elsevierStyleHsp" style=""></span>U/mL (normal <3.5), and myeloperoxidase 0.7<span class="elsevierStyleHsp" style=""></span>U/mL (normal <9.0), both negative. Human histocompatibility antigen, HLA-DR, was also determined as being DRB1*04. The PPD test was nonreactive. The presence of intestinal parasites was also ruled out by conventional tests.</p><p id="par0035" class="elsevierStylePara elsevierViewall">An assessment by the Service of Pneumology suggested a bronchoscopy, and broncho-alveolar lavage (BAL) showed acute and chronic inflammation of the right upper lobe and left upper lobe with non-specific inflammatory reactive changes, where there were lymphocytes, neutrophils and hemosiderin-laden macrophages. Because we failed to establish a definite diagnosis, the patient underwent an endoscopic thoracotomy biopsy of the lingula and posterior left lower lobe, with results compatible with eosinophilic pneumonia (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), ruling out the diagnosis of Churg-Strauss syndrome and Wegener's granulomatosis.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The patient's general condition was stable with no evidence of respiratory failure, cough or fever, so it was decided to treat her only with NSAIDs until the follow-up appointment a month later (diclofenac 100<span class="elsevierStyleHsp" style=""></span>mg/day).</p><p id="par0045" class="elsevierStylePara elsevierViewall">The progression of the patient was satisfactory and after 3 months of follow-up, control studies were performed, showing radiological and tomographic resolution of pneumonia (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Peripheral eosinophilia and immunological studies showed negativity for both the RF 9.13<span class="elsevierStyleHsp" style=""></span>IU/mL (normal <20), and for ANCA, which were undetectable. The patient did not require treatment with corticosteroids or immunosuppressants, and so far, after 3 years of follow-up, the patient remains asymptomatic and serologically negative for autoantibodies.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">CEP was described by Carrington et al. in 1969<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> in a patient with a history of rhinitis and asthma, with dyspnea, fever, peripheral eosinophilia and BAL eosinophils. The patient responded favorably to treatment with glucocorticoids. Series and isolated cases point to immunoallergic disorder as a potential cause since, as mentioned previously, most patients have a history of allergies such as asthma, rhinitis and atopy.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The presence of eosinophilia has been described by several authors in association with some autoimmune diseases such as RA, where this phenomenon has been implicated as a response to inflammatory activity.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Now recognized as being due to the release of cytokines generated in acute inflammatory processes, these proinflammatory cytokines have been identified as interleukin (IL)-6, IL-10, but mainly as IL-5, which, in addition to inducing the production of eosinophilic cells, participates in the inhibition of apoptosis in eosinophils infiltrating the tissue, which explains the greater damage to the target organ.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A number of other cytokines called chemokines have also been identified, mainly eotaxin, which has a greater power for eosinophil chemotaxis and exotaxin-1 and -2, produced by macrophages, monocytes, fibroblasts and T cells (Th2), which are also a major stimulus in the recruitment of eosinophils, and are responsible for their migration and extended stay at the site of the infiltrated tissue inflammation.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Interestingly, we have described elevated levels of eotaxin-1 in patients with RA of recent onset upon analyzing role of proinflammatory cytokines present in this pathology. Syversen et al. described this finding, which could correspond to the original description of the association of eosinophilia to RA.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The presence of eosinophilia is particularly important in some rheumatologic disorders such as Churg-Strauss vasculitis and Wegener's granulomatosis, where its role is crucial in generating the acute inflammatory process in lung<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> tissue. Differential diagnosis with eosinophilic granulomatous vasculitis or Churg-Strauss syndrome is complex, as both share similar clinical and serological manifestations, such as the presence of ANCA in up to 40% of cases and RF.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> According to the description of the disease, 3 clinical stages can be recognized. Our case could be in stage 2, having gone through the prodromal phase of allergic disease (rhinitis), and in the second phase show eosinophilic infiltration in different tissues such as the lung (eosinophilic pneumonia), skin and gastrointestinal system.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> However, the difference is in the histopathological data showing necrotizing vasculitis and extravascular granulomas, absent in CEP.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Payne et al. first described the coexistence of CEP and RA in 1980. They reported the case of a 54-year-old male patient of Indian origin with a diagnosis of RA of 17 years, who developed a picture of CEP.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Other reports have described similar cases with established RA, prior to the presence of clinical symptoms of CEP. Norman et al. described a case with the simultaneous appearance of manifestations of RA and CEP in a 39-year-old whose first manifestation was a dry cough, fever, sweating, fatigue and joint pain, progressing to polyarthritis, establishing the diagnosis of CEP on the basis of clinical criteria and the LBA image but without the presence of peripheral eosinophilia. RF was positive 1:1.280, establishing the diagnosis of RA. Glucocorticoid treatment was administered based on methotrexate and hydroxychloroquine and associated with favorable response, but eventually required treatment with etanercept for control of arthritis. At one year follow-up there was no evidence of pneumonia recurrence.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A second case of simultaneous presentation, referred by Kwaket al., was in an Asian woman, 55, who started with polyarthritis involving small joints of hands, elevated acute phase reactants and a total eosinophils count of 730/mm<span class="elsevierStyleSup">3</span>, in addition to positive RF 243<span class="elsevierStyleHsp" style=""></span>IU/mL. She was treated with parenteral glucocorticoids and treatment for the pneumonia, with improvement of the manifestations of arthritis, subsequently adding methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg/week, descending the dose of oral prednisone. Her progression was favorable, with no recurrence of pneumonia after 18 months of follow-up; however, the authors did not comment on whether the presence of RF persisted over time.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">We described the criteria met to establish a clinical and pathological diagnosis of CEP<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>; however, despite having joint manifestations, we never managed to show objective evidence of acute synovitis, which is essential for the diagnosis of suspected RA, and despite having tested positive for RF and in addition to the DRB1*04 allele, identification of citrullinated peptide antibodies was negative, which together with the absence of arthritis, impeded her classification as RA.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> An important fact is the low titer for c-ANCA autoantigens and x-ANCA, all becoming negative over time as in the case of RF after 3 years of clinical follow-up, persisting undetectable.</p><p id="par0080" class="elsevierStylePara elsevierViewall">We cannot conclude whether there is a link or just a phenomenon of association between patients with established RA and CEP, as in the case of Kwak et al., There is a question of whether over time the patient remained seropositive for RF, or could have had a similar progression to the patient presented here.</p><p id="par0085" class="elsevierStylePara elsevierViewall">A relationship may exist between the two conditions and is probably determined by proinflammatory cytokine production by T cells, which in turn stimulates the production of other cytokines that induce autoantibody production and release eosinophils into the bloodstream, apart from the systemic inflammatory response in the case of RA, and cellular hypersensitivity response in CEP, but we have been unable to clearly establish the link between autoimmune and allergic diseases.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0090" class="elsevierStylePara elsevierViewall">CEP is a clinical condition with an apparently immunoallergic basis, which due to an extensive network of cytokine stimulation and the possible pathogenic role of eosinophils, could be confused with Churg-Strauss syndrome in its eosinophilic clinical phase. The benign course of CEP evidences the difference between the immunoallergic process and autoimmune vasculitis which usually requires chronic treatment with corticosteroids and immunosuppressive agents for control and remission of the disease.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The physician should be aware of the clinical, serological and pathological differences used to establish a correct diagnosis for each of these entities, and thus indicate a specific treatment that allows for the resolution of these pathologies.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres125772" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec113059" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres125771" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec113058" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Description of the Case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of Interests" ] 9 => array:2 [ "identificador" => "xack38110" "titulo" => "Acknowledgment" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-06-21" "fechaAceptado" => "2011-09-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec113059" "palabras" => array:3 [ 0 => "Eosinophillic pneumonia" 1 => "Rheumatoid arthritis" 2 => "Churg Strauss syndrome" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec113058" "palabras" => array:3 [ 0 => "Neumonía eosinofílica" 1 => "Artritis reumatoide" 2 => "Síndrome de Churg-Strauss" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Eosinophilic pneumonia is classified by its acute or chronic presentation, the distinguishing characteristics of which are based on the presence of cough, dyspnea, fever and pulmonary infiltrates with accumulation of inflammatory cells, predominantly eosinophils. The association of eosinophilia and rheumatologic disorders is well known, as in the case of eosinophilic fasciitis and the Churg-Strauss syndrome. The coexistence of chronic eosinophilic pneumonia and rheumatoid arthritis has been reported, either early rheumatoid arthritis of definitive disease. The pathophysiological role of eosinophils in autoimmune diseases is not well defined; however, it has been shown that the production of pro-inflammatory cytokines stimulates and activates different cell groups, and can simultaneously induce autoantibodies and/or increased infiltration of eosinophils in various tissues, without an underlying autoimmune disease. The case of a young woman, with rheumatic chronic eosinophilic pneumonia manifestations and the presence of autoantibodies, which resolved spontaneously, is presented here.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las neumonía eosinofílica se clasifica por su presentación en aguda o crónica; las características distintivas se basan en la presencia de tos, disnea, fiebre e infiltrados pulmonares con acumulación de células inflamatorias, predominante de eosinófilos. La asociación de eosinofilia y padecimientos reumatológicos es bien conocida, como en el caso de la fascitis eosinofílica y el síndrome de Churg-Strauss. La coexistencia de neumonía eosinofílica crónica y artritis reumatoide ha sido reportada, ya sea de inicio coincidente o en artritis reumatoide establecida. El papel fisiopatológico de los eosinófilos en las enfermedades autoinmunes no está bien definido, sin embargo se ha demostrado que la producción de citocinas proinflamatorias estimulan y activan diferentes grupos celulares, pudiendo en forma simultánea inducir autoanticuerpos e incremento y/o infiltración de eosinófilos en diversos tejidos, sin tener una enfermedad autoinmune subyacente. Presentamos el caso de una mujer joven con neumonía eosinofílica crónica con manifestaciones clínicas reumatológicas y presencia de autoanticuerpos, que se resolvió en forma espontánea.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Jaimes-Hernández J, et al. Neumonía eosinofílica crónica: ¿fenómeno autoinmune o enfermedad inmunoalérgica? Reporte de un caso y revisión de literatura. Reumatol Clin. 2012;<span class="elsevierStyleBold">8</span>:145–8.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 497 "Ancho" => 1301 "Tamanyo" => 87116 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Chest radiograph showing a pulmonary consolidation area in the left upper hemithorax. (B) Axial CT at the level of the tracheal carina showing peripheral areas of consolidation in both hemithorax.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 831 "Ancho" => 1002 "Tamanyo" => 143647 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Endoscopic biopsy of lung showing interstitial expansion, edema, accompanied by mixed lymphoid infiltrate composed of lymphocytes, neutrophils and eosinophils (arrow). Hematoxylin and eosin 40×.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 584 "Ancho" => 853 "Tamanyo" => 56052 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">High-resolution CT scan with lung window, which after 3 months of follow-up shows complete resolution of pneumonic inflammation.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic eosinophilic pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.B. Carrington" 1 => "W.W. 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Carrillo-Ponce, of the Pathology Department of ISSEMYM, who kindly collaborated in the description of the histological studies.</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000000800000003/v1_201305061639/S2173574312000111/v1_201305061639/en/main.assets" "Apartado" => array:4 [ "identificador" => "17376" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Case Report" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000800000003/v1_201305061639/S2173574312000111/v1_201305061639/en/main.pdf?idApp=UINPBA00004M&text.app=https://www.reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312000111?idApp=UINPBA00004M" ]
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| 2024 June | 118 | 37 | 155 |
| 2024 May | 110 | 65 | 175 |
| 2024 April | 111 | 38 | 149 |
| 2024 March | 117 | 64 | 181 |
| 2024 February | 82 | 37 | 119 |
| 2024 January | 90 | 40 | 130 |
| 2023 December | 81 | 45 | 126 |
| 2023 November | 91 | 51 | 142 |
| 2023 October | 99 | 43 | 142 |
| 2023 September | 144 | 41 | 185 |
| 2023 August | 97 | 27 | 124 |
| 2023 July | 85 | 28 | 113 |
| 2023 June | 89 | 37 | 126 |
| 2023 May | 82 | 27 | 109 |
| 2023 April | 96 | 18 | 114 |
| 2023 March | 95 | 36 | 131 |
| 2023 February | 120 | 34 | 154 |
| 2023 January | 87 | 20 | 107 |
| 2022 December | 108 | 39 | 147 |
| 2022 November | 129 | 40 | 169 |
| 2022 October | 102 | 38 | 140 |
| 2022 September | 77 | 33 | 110 |
| 2022 August | 98 | 45 | 143 |
| 2022 July | 90 | 50 | 140 |
| 2022 June | 119 | 39 | 158 |
| 2022 May | 136 | 51 | 187 |
| 2022 April | 155 | 68 | 223 |
| 2022 March | 129 | 69 | 198 |
| 2022 February | 135 | 37 | 172 |
| 2022 January | 127 | 49 | 176 |
| 2021 December | 119 | 45 | 164 |
| 2021 November | 126 | 55 | 181 |
| 2021 October | 114 | 67 | 181 |
| 2021 September | 86 | 54 | 140 |
| 2021 August | 84 | 46 | 130 |
| 2021 July | 77 | 38 | 115 |
| 2021 June | 127 | 50 | 177 |
| 2021 May | 140 | 65 | 205 |
| 2021 April | 240 | 107 | 347 |
| 2021 March | 182 | 51 | 233 |
| 2021 February | 91 | 29 | 120 |
| 2021 January | 95 | 27 | 122 |
| 2020 December | 96 | 28 | 124 |
| 2020 November | 173 | 35 | 208 |
| 2020 October | 139 | 23 | 162 |
| 2020 September | 93 | 46 | 139 |
| 2020 August | 61 | 21 | 82 |
| 2020 July | 69 | 38 | 107 |
| 2020 June | 65 | 20 | 85 |
| 2020 May | 70 | 13 | 83 |
| 2020 April | 50 | 19 | 69 |
| 2020 March | 26 | 11 | 37 |
| 2020 February | 1 | 0 | 1 |
| 2019 May | 1 | 0 | 1 |
| 2019 January | 1 | 0 | 1 |
| 2018 May | 8 | 1 | 9 |
| 2018 April | 127 | 19 | 146 |
| 2018 March | 138 | 20 | 158 |
| 2018 February | 75 | 10 | 85 |
| 2018 January | 88 | 13 | 101 |
| 2017 December | 85 | 19 | 104 |
| 2017 November | 103 | 11 | 114 |
| 2017 October | 100 | 13 | 113 |
| 2017 September | 115 | 10 | 125 |
| 2017 August | 85 | 26 | 111 |
| 2017 July | 100 | 12 | 112 |
| 2017 June | 129 | 30 | 159 |
| 2017 May | 152 | 23 | 175 |
| 2017 April | 96 | 23 | 119 |
| 2017 March | 144 | 26 | 170 |
| 2017 February | 315 | 21 | 336 |
| 2017 January | 138 | 21 | 159 |
| 2016 December | 171 | 25 | 196 |
| 2016 November | 191 | 16 | 207 |
| 2016 October | 237 | 13 | 250 |
| 2016 September | 300 | 22 | 322 |
| 2016 August | 266 | 19 | 285 |
| 2016 July | 109 | 13 | 122 |
| 2016 May | 1 | 0 | 1 |
| 2016 April | 1 | 0 | 1 |
| 2016 January | 1 | 0 | 1 |
| 2015 December | 2 | 0 | 2 |
| 2015 September | 1 | 0 | 1 |
| 2015 August | 2 | 0 | 2 |
| 2015 July | 80 | 5 | 85 |
| 2015 June | 111 | 13 | 124 |
| 2015 May | 180 | 23 | 203 |
| 2015 April | 111 | 22 | 133 |
| 2015 March | 168 | 10 | 178 |
| 2015 February | 208 | 17 | 225 |
| 2015 January | 154 | 19 | 173 |
| 2014 December | 154 | 13 | 167 |
| 2014 November | 162 | 13 | 175 |
| 2014 October | 166 | 26 | 192 |
| 2014 September | 105 | 14 | 119 |
| 2014 August | 87 | 17 | 104 |
| 2014 July | 91 | 23 | 114 |
| 2014 June | 130 | 22 | 152 |
| 2014 May | 105 | 22 | 127 |
| 2014 April | 92 | 17 | 109 |
| 2014 March | 101 | 27 | 128 |
| 2014 February | 101 | 30 | 131 |
| 2014 January | 117 | 31 | 148 |
| 2013 December | 94 | 18 | 112 |
| 2013 November | 72 | 27 | 99 |
| 2013 October | 88 | 22 | 110 |
| 2013 September | 86 | 29 | 115 |
| 2013 August | 81 | 40 | 121 |
| 2013 July | 80 | 38 | 118 |
| 2013 June | 84 | 33 | 117 |
| 2013 May | 96 | 47 | 143 |
| 2013 April | 80 | 54 | 134 |
| 2013 March | 76 | 51 | 127 |
| 2013 February | 65 | 28 | 93 |
| 2013 January | 69 | 25 | 94 |
| 2012 December | 74 | 46 | 120 |
| 2012 November | 66 | 46 | 112 |
| 2012 October | 55 | 32 | 87 |
| 2012 September | 14 | 2 | 16 |
| 2012 July | 6 | 0 | 6 |
| 2012 June | 13 | 0 | 13 |
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