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Scientific Letter
Counterintuitive Pulmonary Nodules in Rheumatoid Arthritis
Nódulos pulmonares contraintuitivos en artritis reumatoide
Felix Daniel Zamoraa,
Corresponding author
zamo0038@umn.edu

Corresponding author.
, Eitan Podgaetzb, H. Erhan Dincera
a Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, MN, United States
b Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN, United States
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a significant cause of morbidity and mortality in developed countries&#44; with a prevalence of 0&#46;5&#37;&#8211;1&#37; and an incidence of 5&#8211;50 per 100<span class="elsevierStyleHsp" style=""></span>000&#46; Nodulosis is the most common extra-articular manifestation and occurs in 25&#37; of RA patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Pulmonary manifestations are broad and include necrobiotic nodules&#44; infections&#44; drug induced lung injury&#44; obliterative bronchiolitis&#44; interstitial lung disease&#44; bronchiectasis&#44; and malignancy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Tumor necrosis factor &#40;TNF&#41; is an overexpressed pro-inflammatory cytokine in RA patients&#44; and the American College of Rheumatology has formal recommendations on the use of anti-TNF biologic agents in RA patients with poor prognostic factors&#46; We report a case of a 50-year-old female developing multifocal nodular consolidations&#44; with and without cavitation &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and C&#41;&#44; one month after initiation of etanercept&#46; Immunosuppressive drugs were suspended and a bronchoalveolar lavage of the left upper lobe and lingula were negative for an infectious etiology&#46; Devoid of a confirmed infection&#44; her RA medications were restarted&#44; except for etanercept&#46; Serial CT imaging demonstrated interval regression of the nodules&#46; Radiographic changes were seen at the two-month follow up CT&#44; and have remained unchanged at nine months &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and D&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Etanercept-associated nodular disease case reports have varied from new pulmonary nodules with histopathology typical of pulmonary RA nodules&#44; histopathology consistent with sarcoidosis&#44; and histopathology of lymphohistiocytic infiltrates not typical of either&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;4</span></a> Treatments for etanercept-associated PN have varied&#44; but typically involve corticosteroids and drug withdrawal&#46; There have also been two case reports highlighting the evolution of the nodules with continued etanercept therapy&#44; illustrating the regression of nodules as well as stability of nodules without progression despite continued etanercept therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This case exemplifies that a recombinant human TNF receptor fusion protein may contribute to the counterintuitive formation of granulomatous disease and pulmonary nodulosis&#46; Many mechanisms have been proposed&#44; but the exact mechanism leading to pulmonary nodulosis is not currently known&#46; It has been proposed that the increased size or formation of pulmonary nodules may be related to the increased size of necrotic centers&#44; a result of the reduction of soluble TNF leading to an exaggerated or altered effect on other inflammatory pathways&#44; or even directly related to the RA progression and not directly related to the therapeutic agent&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; we appreciate that PN is not uncommon in RA patients&#44; but recommend that etanercept-related PN be considered as part of the differential diagnosis&#46; Bronchoalveolar lavage should remain integral to the evaluation&#44; but if unrevealing it would be reasonable to withhold etanercept followed by repeat imaging in 6&#8211;8 weeks&#46; If the nodules are stable or regress&#44; than serial imaging would be a reasonable approach&#46; Progressive disease should be further investigated&#46; Consideration of etanercept as the etiology of new pulmonary nodules may decrease morbidity associated with unnecessary invasive diagnostic procedures associated with nodule work up&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Zamora FD&#44; Podgaetz E&#44; Dincer HE&#46; N&#243;dulos pulmonares contraintuitivos en artritis reumatoide&#46; Arch Bronconeumol&#46; 2016&#59;52&#58;334&#8211;335&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">CT of chest &#40;A&#41;&#44; initial CT demonstrating left upper lobe nodule with cavitation &#40;B&#41;&#44; nine month follow-up CT with resolution of left upper lobe nodule&#44; &#40;C&#41; initial CT demonstrating peripheral nodule in the lingual and &#40;D&#41; nine month follow-up CT with resolution of peripheral nodule in the lingual&#46;</p>"
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