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including malignancies<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> and secondary autoimmune disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 62-year-old woman&#44; former smoker of 15 pack-years&#44; with a 10-year history of palindromic rheumatism that progressed to RA with bone erosion&#46; She received treatment with various disease-modifying antirheumatic drugs &#40;DMARD&#41;&#44; such as hydroxychloroquine sulfate&#44; methotrexate&#44; and gold salts&#44; together with NSAIDs &#40;indomethacin and naproxen&#41; and low-dose prednisone&#44; depending on her symptoms&#44; at different disease stages&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Between May 2010 and March 2012&#44; due to a lack of response to DMARDs&#44; she received biological treatment with anti-TNF&#945; &#40;etanercept&#41; for the first time&#44; with improvement of her joint symptoms&#46; In March 2016&#44; when she was receiving treatment with methotrexate &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#41; for a new flare&#44; etanercept was reintroduced &#40;50<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#41;&#44; again resulting in clinical improvement&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In a radiological follow-up of the disease&#44; when the patient was asymptomatic&#44; a chest X-ray and computed tomography &#40;CT&#41; were obtained&#44; showing 2 solid cavitating nodules&#44; one measuring 15<span class="elsevierStyleHsp" style=""></span>mm in the apicoposterior segment of the left upper lobe &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41; and the other 24<span class="elsevierStyleHsp" style=""></span>mm in the upper segment of the lingula &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Laboratory tests&#44; including complete blood count&#44; coagulation&#44; blood biochemistry&#44; and tumor markers&#44; were normal&#46; CRP and ESR were 0&#46;42<span class="elsevierStyleHsp" style=""></span>ng&#47;dl and 27<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#44; respectively&#46; Autoimmune tests showed elevated cyclic citrullinated peptide antibodies &#40;381<span class="elsevierStyleHsp" style=""></span>IU&#41; and rheumatoid factor &#40;200<span class="elsevierStyleHsp" style=""></span>IU&#41;&#44; with values similar to previous determinations&#46; Basic urine profile showed no significant changes&#46; Serum anti-neutrophil cytoplasmic antibodies determined by immunofluorescence were negative&#44; as was ELISPOT-TB&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Fiberoptic bronchoscopy was performed&#44; showing no endobronchial abnormalities&#44; and microbiological and cytological studies of the bronchial aspirate and bronchoalveolar lavage were negative&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Positron emission tomography was also performed&#44; showing annular&#44; irregular 18F-fluorodeoxyglucose uptake limited to the pulmonary nodules&#44; with a SUVmax of 2&#46;9 in the lesion located in the left upper lobe and 3&#46;1 in the lesion located in the lingula&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A pulmonary biopsy was obtained from the lingular lesion using CT-guided Tru-Cut&#46; Histopathological study showed a granulomatous inflammatory lesion associated with vasculitis consistent with granulomatosis with polyangiitis &#40;formerly known as Wegener&#39;s granulomatosis&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of the diagnostic suspicion of granulomatosis with polyangiitis associated with the administration of etanercept&#44; this drug was discontinued and treatment began with prednisone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day in a tapering regimen&#44; and the background biological treatment was replaced by tocilizumab &#40;8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;month&#41;&#46; Chest CT 3 months later showed resolution of the lesions&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The exclusion of other pulmonary complications&#44; the temporal association with the administration of etanercept&#44; and the rapid and complete resolution of the pulmonary lesions after its withdrawal and subsequent treatment with corticosteroids confirm the diagnosis of vasculitis associated with etanercept&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The spectrum of pulmonary manifestations of RA is wide and includes involvement of the parenchyma &#40;interstitial lung disease&#44; pulmonary nodules&#41;&#44; airway &#40;bronchiolitis obliterans&#44; bronchiectasis&#41;&#44; pleura &#40;effusion&#44; bronchopleural fistula&#44; pneumothorax&#41;&#44; and the pulmonary vasculature &#40;pulmonary hypertension&#44; thromboembolic disease&#41;&#44; that may precede joint symptoms in 10&#37;&#8211;20&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> This case shows that the differential diagnosis must also include side effects of immunomodulatory therapy &#40;toxicity&#44; infection&#41; used in the treatment of these patients&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The mechanisms causing anti-TNF&#945; to trigger antibody formation and autoimmune processes are not fully clarified&#46; There is evidence that treatment with anti-TNF&#945; is associated with a higher production of antinuclear antibodies&#44; depending on the type of anti-TNF&#945; used&#46; In the case of etanercept&#44; antinuclear antibody levels range from 11&#37; to 54&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">7&#8211;9</span></a> and this has also been associated with the development of other autoimmune diseases&#44; such as leukocytoclastic vasculitis&#44; accelerated rheumatoid nodulosis&#44; and vasculitis associated with anti-neutrophil cytoplasmic antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> Clinical manifestations are variable&#44; and patients&#44; like ours&#44; often have no associated systemic symptoms&#46; Vasculitis associated with anti-TNF&#945; therapy is a rare complication&#44; and in most cases the presentation is exclusively cutaneous<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a>&#59; pulmonary involvement in these patients is unusual&#46; Ramos-Casals et al&#46; reported a series of 233 patients with anti-TNF&#945;-induced autoimmune diseases&#44; including 133 cases of vasculitis&#46; Of these&#44; only 3 were pulmonary &#40;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a> Treatment consisted of discontinuing the drug and administering corticosteroids&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion&#44; while anti-TNF&#945; offers clear advantages in the management of RA&#44; these biologics should be used with caution and under close monitoring&#44; particularly in patients with pre-existing lung disease&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> If lesions and&#47;or pulmonary infiltrates develop during treatment with anti-TNF&#945; the first step is to rule out infectious processes&#46; If results are inconclusive&#44; infiltrates are persistent&#44; and the index of suspicion is high&#44; invasive tests such as transbronchial biopsy&#44; cryobiopsy&#44; CT-guided biopsy&#44; or even surgical biopsy are recommended in order to obtain a definitive diagnosis and to indicate the correct treatment&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mart&#237;n-de Le&#243;n R&#44; Mois&#233;s J&#44; Peris P&#44; Agust&#237; C&#44; Marrades RM&#46; N&#243;dulos pulmonares cavitados en paciente tratada con anti-TNF&#46; Arch Bronconeumol&#46; 2018&#59;54&#58;431&#8211;432&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Chest CT showing a cavitating nodular lesion in the left upper lobe and &#40;B&#41; another in the upper segment of the lingula&#46; &#40;C&#41; Staining of elastic fibers to highlight the irregular destruction of the arterial wall by the inflammatory process&#46; Necrosis is seen in the upper right corner&#46; Orcein 200&#215;&#46;</p>"
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