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      IgG4-related pleural disease in a patient with pulmonary adenocarcinoma under durvalumab treatment: a case report

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          Abstract

          Background

          Immune checkpoint inhibitors (ICIs) are the standard treatment for non-small cell lung cancer. The unique adverse events that can arise after treatment with ICIs are known as immune-related adverse events (irAE). As the number of cases under treatment with ICIs increases, new types of characteristics of irAE have emerged. This case report suggests that IgG4-related pleural disease could occur as an irAE.

          Case presentation

          A 64-year-old man was diagnosed with pulmonary adenocarcinoma stage IIIB. Following concurrent chemoradiotherapy, durvalumab was administered every two weeks. The patient complained of dyspnea on effort 4 months after the initiation of durvalumab therapy. Chest CT scans showed mild bilateral pleural effusion 4 months after the initiation of durvalumab therapy, and the amount of pleural effusion increased further at 7 months. Durvalumab was thought to be a potential cause of pleural effusion and was withdrawn after 13 courses of administration over 7 months. The level of serum IgG4 was 2750 mg/dL. The levels of IgG4 of the pleural fluids were 2790 mg/dL on the right side and 2890 mg/dL on the left side at 7 months. Microscopic examination of the pleural biopsy revealed lymphoplasmacytic infiltration with storiform fibrosis. Immunohistochemical examinations showed that the number of IgG4-positive cells was > 20/high power field and the percentage of IgG4-positive to IgG-positive plasma cells was > 50%. Oral prednisolone at a dose of 30 mg/day was initiated, and remarkable clinical improvements were achieved. After 4 months of prednisolone therapy, the level of serum IgG4 decreased to 370 mg/dL and chest CT revealed the disappearance of bilateral pleural effusion.

          Conclusion

          This was a case of IgG4-related pleural disease in a patient with pulmonary adenocarcinoma under durvalumab treatment. To our knowledge, this is the first case report of IgG4-related pleural disease as an irAE. It is important to consider the possibility of IgG4-related pleural disease in cases of pleural effusion during the treatment with ICIs.

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          Most cited references11

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          IgG4-related disease.

          Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear.
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            A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

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              IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases.

              Immunoglobulin G4 (IgG4)-related disorders can occur in the respiratory system. However, the clinicopathologic characteristics have not been well clarified. In this study, we examined clinical and pathologic features of, and follow-up data on, IgG4-related lung and pleural lesions. The patients group consisted of 17 males and 4 females with an average age of 69 years (range: 42 to 76). Pulmonary lesions in 16 patients and pleural lesions in 5 patients were examined. Histologically, all lesions showed diffuse lymphoplasmacytic infiltration. Irregular fibrosis and obliterative vascular changes were more common in solid areas. Nine cases (43%) had eosinophilic infiltration with more than 5 cells per high-power field. Immunostaining revealed numerous IgG4-positive plasma cells in inflamed areas. Sclerosing inflammation was distributed with intrapulmonary connective tissue. Pulmonary lesions showed a variety of morphologic changes according to the predominant area of inflammation. Serum IgG4 concentrations were elevated in 9 of 11 patients tested (average 6.9 g/L; range 0.3 to 18.0 g/L; normal range <1.35 g/L). Extra-pulmonary and extra-pleural IgG4-related lesions were identified in 9 patients (43%), and developed simultaneously or asynchronously during follow up. All patients treated with steroids responded, but some radiologic abnormalities remained in 3 patients. Interestingly, 1 patient was found to have a primary adenocarcinoma against a background of IgG4-related lung disease during follow up. In conclusion, IgG4-related diseases show a greater variety of pulmonary and pleural lesions than previously thought. It is important, therefore, to know the morphologic variety and clinicopathologic characteristics of this disorder.
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                Author and article information

                Contributors
                terasima@tdc.ac.jp
                okavango33et@gmail.com
                tkssmd.z7@gmail.com
                aoik02aoik02@gmail.com
                tmatsuzaki@tdc.ac.jp
                tnakajima@tdc.ac.jp
                sasakiaya@tdc.ac.jp
                keguchi@tdc.ac.jp
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                25 April 2020
                25 April 2020
                2020
                : 20
                : 104
                Affiliations
                [1 ]ISNI 0000 0004 0640 4858, GRID grid.417073.6, Department of Respiratory Medicine, , Tokyo Dental College Ichikawa General Hospital, ; 5-11-13 Sugano, Ichikawa, Chiba, 272-0824 Japan
                [2 ]ISNI 0000 0004 0640 4858, GRID grid.417073.6, Department of Pathology and Laboratory Medicine, , Tokyo Dental College Ichikawa General Hospital, ; 5-11-13 Sugano, Ichikawa, Chiba, 272-0824 Japan
                [3 ]ISNI 0000 0004 0640 4858, GRID grid.417073.6, Department of Surgery, , Tokyo Dental College Ichikawa General Hospital, ; 5-11-13 Sugano, Ichikawa, Chiba, 272-0824 Japan
                Author information
                http://orcid.org/0000-0002-4353-7647
                Article
                1150
                10.1186/s12890-020-1150-x
                7183131
                32334571
                4eecb1fd-c209-4d81-9363-9f6bb0687e50
                © The Author(s). 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 13 November 2019
                : 15 April 2020
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                durvalumab,igg4-related pleural disease,immune checkpoint inhibitors,immune-related adverse events,lung cancer

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