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      Progressive dyspnea and diffuse ground‐glass opacities after treatment for lymphoma with rituximab‐containing chemotherapy: A case report

      case-report

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          Abstract

          A 49‐year‐old man presented to our outpatient clinic complaining of nonproductive cough and exertional dyspnea for two months. He had been diagnosed with large B cell non‐Hodgkin's lymphoma seven months previously, and the tumor had almost disappeared after four cycles of rituximab‐containing chemotherapy. He then developed a severe dry cough, progressive dyspnea and hypoxia two weeks after the fifth cycle. Bilateral diffuse ground‐glass opacities were visible on chest X‐ray. Although the patient's symptoms were ameliorated temporarily after two weeks of methylprednisolone administration and multiple antibiotics, exertional dyspnea had progressed slowly starting one month after discontinuation of the corticosteroid. A repeat chest computed tomography (CT) scan showed diffuse ground‐glass opacities, bronchoalveolar lavage fluid tests for pathogens were negative and the pathological manifestation of the transbronchial lung biopsy showed nonspecific interstitial pneumonia. Rituximab‐induced interstitial lung disease was diagnosed after multidisciplinary discussion. Prednisone was again prescribed and his symptoms and the pulmonary opacities gradually disappeared. Although various pulmonary infections are the most common respiratory complications in patients with non‐Hodgkin's lymphoma undergoing rituximab‐containing chemotherapy, noninfectious diffuse lung disease, eg, drug‐associated interstitial lung disease might be considered as a differential diagnosis of patients treated with rituximab, especially if a patient is nearing the time of administration of a fourth cycle of rituximab.

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          Most cited references8

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          Pneumocystis pneumonia in patients treated with rituximab.

          Pneumocystis pneumonia (PcP) is an opportunistic fungal infection. Although T-cell immunity is classically related to Pneumocystis defense, recent data support roles for B lymphocytes in the development of PcP in animals, and we have observed several cases of PcP in patients receiving rituximab. These observations prompted a systematic review of our experience to define the spectrum of clinical presentations in which PcP has occurred in the setting of rituximab therapy. Using a computer-based search, we reviewed the records of patients who received rituximab and developed PcP at Mayo Clinic Rochester over the years 1998 to 2011 to establish the underlying conditions, clinical course, possible risk factors, and potential association between this drug and the development of PcP. Over this period, 30 patients developed PcP during treatment with rituximab. The underlying diseases included hematologic malignancies in 90% of cases. Glucocorticoids were used in 73% of these patients, under different chemotherapeutic regimens. Three patients (10%) developed PcP in the setting of rituximab without concomitant chemotherapy or significant glucocorticoid exposure. Of these 30 patients, 88% developed acute hypoxemic respiratory failure and 53% required ICU admission. The clinical course was fatal in 30%. PcP can occur in association with rituximab, with the majority of cases having also received cytotoxic chemotherapy or significant doses of glucocorticoids. The clinical course of cases of PcP in patients treated with rituximab can be quite fulminant, with significant mortality. Primary prophylaxis should be considered in patients at risk, and secondary prophylaxis provided unless immune reconstitution is well assured.
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            Rituximab-induced lung disease: A systematic literature review.

            The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab. A systematic literature review was performed on English-language reports in PubMed until September 2008. Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease. Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.
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              Non-infectious pulmonary toxicity of rituximab: a systematic review.

              Rituximab (RTX), a B-cell depleting mAb, has been reported to cause pulmonary toxicity in many patients. As the use of this biologic is increasing, we have undertaken a systematic review of the literature to gauge the nature and extent of non-infection-related RTX-induced lung disease. A systematic literature review was undertaken to document all reported cases of RTX-associated interstitial lung disease (RTX-ILD), evaluating the epidemiological, clinical, radiological, histopathological, laboratory and management data from the available primary sources. The search was conducted using PubMed, the Cochrane Library and EMBASE up to June 2010 using the terms RTX in the advanced search option without limitations and all relevant publications reviewed manually. In addition, unpublished data from the Food and Drug Administration, the European Medicines Agency and the manufacturer (Roche) were evaluated to complement this search. Identified articles were included if they displayed a potential relationship between the administration of RTX and ILD following exclusion of other likely causes. A total of 121 cases of potential RTX-ILD were identified from 21 clinical studies/trials, 30 case reports and 10 case series. The most common indication for RTX was diffuse large B-cell lymphoma. RTX-ILD occurred more frequently in male patients and was most common during the fifth and sixth decades of life. In most cases, RTX was part of combination chemotherapy, but in 30 (24.7%) cases it was given as monotherapy. The mean and median number of cycles of RTX before disease onset was four, but cases following the first cycle or as late as the 12th cycle were also identified. The mean time of onset, from the last RTX infusion until symptom development or relevant abnormal radiological change was 30 days (range 0-158 days). Abnormal radiological findings were similar in all patients, with diffuse bilateral lung infiltrates apparent on chest radiographs and/or thoracic CT. Hypoxaemia was seen in all cases and pulmonary function tests were uniformly abnormal with a characteristic diffusion capacity deficit and restrictive ventilatory pattern. RTX-ILD was fatal in 18 cases. ILD is a rare but potentially fatal complication of RTX therapy. This diagnosis should be considered in any patient who develops respiratory symptoms or new radiographic changes while receiving this biologic agent.
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                Author and article information

                Contributors
                pumchhh@126.com
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                06 May 2020
                July 2020
                : 11
                : 7 ( doiID: 10.1111/tca.v11.7 )
                : 2040-2043
                Affiliations
                [ 1 ] Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 2 ] Radiological Department Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 3 ] Pathological Department Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 4 ] International Medical Service Department Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 5 ] Medical Research Center, Central Laboratory Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                Author notes
                [*] [* ] Correspondence

                Hui Huang, Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, Beijing, China, 100730.

                Tel: 86‐10‐69155039.

                Fax: 86‐10‐69155039.

                Email: pumchhh@ 123456126.com

                Author information
                https://orcid.org/0000-0001-7184-0005
                https://orcid.org/0000-0002-1609-9901
                Article
                TCA13473
                10.1111/1759-7714.13473
                7327694
                32374517
                f89702aa-301c-4474-9975-f63bdedecd30
                © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 March 2020
                : 18 April 2020
                : 19 April 2020
                Page count
                Figures: 2, Tables: 0, Pages: 4, Words: 2429
                Funding
                Funded by: Chinese Academy of Medical Sciences Clinical and Transitional Research Fund
                Award ID: 2019XK320037
                Funded by: Chinese National Natural Science Fund Youth Fund project
                Award ID: 81600050
                Funded by: National Key Research and Development Program of China , open-funder-registry 10.13039/501100012166;
                Award ID: 2016YFC0901500
                Categories
                Case Report
                Case Reports
                Custom metadata
                2.0
                July, 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:01.07.2020

                drug associated lung disease,ground‐glass opacities,lymphoma,rituximab

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