Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report

Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report Chun-Ying Chou, Min-Shu Hsieh, Ping-Hung Kuo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4014771/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. To our knowledge, only three cases of combined MG and DPB have been reported. Case presentation: A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. The patient had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Physical examination revealed coarse breathing sounds with inspiratory crackles. Chest computed tomography scan revealed progressive diffuse bronchitis and bronchiolitis. DPB was confirmed on video-assisted thoracoscopic surgery lung biopsy, and sputum culture showed the presence of Pseudomonas aeruginosa . The patient’s respiratory symptoms improved after treatment with oral azithromycin, levofloxacin, and the transient use of inhaled amikacin. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia, with an arterial partial pressure of carbon dioxide measuring 78.6 mmHg, requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Muscle weakness responded to pyridostigmine and corticosteroids. However, she was readmitted after several months because of another episode of P. aeruginosa-related respiratory infection. Currently, she is in stable condition with long-term maintenance therapies comprising pyridostigmine, corticosteroid, azithromycin, and inhaled amikacin. Conclusions To best of our knowledge, this might be the first case of sequential development of DPB followed by PTMG. The coexistence of DPB and PTMG poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapy for MG. Diffuse panbronchiolitis Myasthenia gravis Thymoma Thymic neoplasm Case report Figures Figure 1 Figure 2 Figure 3 Background Thymomas and thymic carcinomas are rare primary tumors located in the mediastinum, and derived from the thymic epithelium. Myasthenia gravis (MG) is the most prevalent type of paraneoplastic syndrome associated with these tumors.[ 1 ] Approximately 30% of patients with thymoma either present with or develop MG.[ 2 , 3 ] Thymectomy should be performed as an oncological intervention if a thymoma is identified or strongly suspected to prevent local compression and possible spread to the thoracic cavity.[ 4 ] Nevertheless, after thymectomy, patients can develop post-thymectomy myasthenia gravis (PTMG). PTMG refers to the subsequent development of MG after radical surgical resection in patients with thymoma who did not exhibit any signs of MG before surgery. PTMG might be misdiagnosed not only because of its rare incidence, which has been reported to be between 0.97% and 13.39% in previous studies, but also due to the uncertain interval between the removal of thymoma and the new onset of PTMG, which can range from 3 days to over 14 years.[ 5 ] Bronchiectasis has been recognized as a potential complication associated with thymic neoplasms, and there have been reports of diffuse panbronchiolitis (DPB) occurring in conjunction with these neoplasms as well. Both bronchiectasis and DPB are potentially raised from an aberrant immune response involving lymphocytes.[ 6 ] Based on what we know, there have been only three reported cases of concurrent MG and DPB. Notably, MG was diagnosed simultaneously with thymoma in all three cases. Herein, we present a patient who developed DPB and PTMG sequentially several years after thymectomy. Case presentation A 45-year-old Taiwanese woman who had a productive cough for 1.5 years, presented at our hospital. The patient also complained of symptoms such as rhinorrhea, anosmia, intermittent ear fullness, shortness of breath, and an 18% weight loss within half a year. She had no fever, chest pain, hemoptysis, or night sweating. She never smoked. Further, she had undergone robot-assisted thymectomy, along with lymph node dissection, for B2-type thymoma 7 years back. After surgery, she received adjuvant radiotherapy targeting the tumor bed in the anterior mediastinum. The cumulative dose administered was 5,400 cGy divided into 30 fractions. Chest computed tomography (CT) scan was conducted every 6 months after surgery. The anterior mediastinum presented with postoperative changes. Further, the medial aspect of the left upper lobe presented with post-irradiation changes and subpleural fibrosis. However, 6 years after the surgery, subsequent follow-up chest CT scans revealed increased diffuse bronchitis and bronchiolitis over both lungs ( Fig. 1 a, b, c ) , without evidence of recurrent thymoma. The patient also presented with rhinorrhea, anosmia and ear fullness. Thus, she was referred to the otolaryngologist’s outpatient clinic for further evaluation. Sinus CT scan imaging and local findings confirmed the diagnosis of chronic bilateral pansinusitis and chronic left otitis media. She was prescribed with short-course therapy of oral clarithromycin at a dosage of 500 mg/day and nasal irrigation was recommended. However, despite these interventions, the symptoms persisted intermittently and did not completely resolve. The patient was admitted to the ward for further evaluation of the underlying etiology. Physical examination revealed coarse breathing sounds with inspiratory crackles. Chest CT scan revealed diffuse bronchial wall thickening and mild bronchiectasis with multiple centrilobular nodules, ground-glass nodules, and air trapping ( Fig. 1 d, e, f ) . The pulmonary function test showed that the ratio of the forced expiratory volume in 1 s to forced vital capacity was 77.6%. The forced vital capacity (FVC) was 1.61 L, which was 53.1% of the predicted value. This finding indicated mixed obstructive and restrictive ventilatory defect. Anti-neutrophil cytoplasmic antibodies, the level of serum total immunoglobulin-E, and blood eosinophil counts were checked to identify the underlying etiologies of sinopulmonary syndrome and was found to be within the normal range. Serum immunoglobulin tests also showed no signs of hypogammaglobulinemia. Bronchial alveolar lavage showed no evidence of fungal or Mycobacterial infection. To investigate the underlying etiologies, video-assisted thoracoscopic surgery (VATS) lung biopsy was conducted. The pathological biopsy report confirmed the DPB diagnosis ( Fig. 2 ) . After DPB diagnosis, azithromycin at a dose of 500 mg/day was prescribed. In the event of worsening symptoms, the patient received short-term treatment with amikacin inhalation. Moreover, oral levofloxacin was due to the presence of Pseudomonas aeruginosa in the previous sputum culture. The patient presented with significant improvement in symptoms including productive cough. Nevertheless, 3 months after DPB diagnosis, the patient experienced a gradual onset of symptoms, which included facial weakness, head drop, diplopia, and proximal muscle weakness. Subsequently, she had ptosis with diurnal fluctuations and dysphagia. Arterial blood gas analysis revealed hypercapnia with a partial carbon dioxide pressure of 78.6 mmHg, a bicarbonate level of 39.9 mmol/l, and a pH of 7.32. Noninvasive positive pressure ventilation support was administered. The pulmonary function test revealed deteriorated FVC ( Table 1 ) . Due to the aforementioned symptoms, the acetylcholine receptor antibody test was conducted. Results revealed a high level of acetylcholine receptor antibody at 7.616 nmol/l, which is significantly above the normal range (< 0.2 nmol/l). The repetitive stimulation test also showed a decremental change in the resting and postexercise test results. These findings indicated an abnormality at the neuromuscular junction. Thus, the patient was diagnosed with MG ( Fig. 3 ) . Table 1 Diagnostic timeline and serial respiratory function test results. Month (M) VATS biopsy 3 M (MG) 4 M 8 M 10 M FVC (% predicted) 53.1 49.1 68.1 52.5 52.6 PImax/Pemax (cmH 2 O) NA NA −81/+107 −52/+50 −88/+92 Treatment with prednisolone at a daily dose of 0.5 mg/kg and pyridostigmine bromide at a dose of 60 mg four times a day was initiated. Thereafter, ptosis resolved and proximal weakness improved. Consequently, the patient was gradually weaned off noninvasive positive pressure ventilation support. The patient was dependent on prednisolone at a dose of 30 mg on alternate days. She reported worsened weakness at the lower dosage. Azithromycin regimen was administered daily for DPB, and intermittent short-course levofloxacin was administered if purulent sputum was noted. However, after several months later, the patient was readmitted because of another episode of P. aeruginosa -related respiratory infection complicated by desaturation. She received intravenous antibiotics to manage the infection. After successfully controlling the infection, the patient has achieved a stable condition and is receiving long-term maintenance therapies, with pyridostigmine, corticosteroids, azithromycin, and inhaled amikacin. Discussion and Conclusions In this report, we describe a case who develops DPB and PTMG sequentially several years after thymectomy for thymoma. We presented a complex clinical course and diagnostic challenge, and under careful clinical assessment, the patient was diagnosed and treated correctly and appropriately in a timely manner. DPB typically manifests between the ages of 20 and 50, with a higher prevalence in males compared to females. This disease primarily affects individuals in Asian populations. Certain HLA types have been found to be associated with the disease.[ 7 ] Greater than 80% of patients with DPB have a history of chronic paranasal sinusitis, or they continuously present with the condition.[ 7 ] In the current case, the patient was initially diagnosed with sinusitis, which exhibited features consistent with those described in the literature. To assess the association between thymoma and DPB, we evaluated the data of 16 patients from reports published in PubMed, Medline, and Web of Science, using the terms “diffuse panbronchiolitis” and “thymoma” or “thymic carcinoma” ( Table 2 ) . Eight patients concomitantly experienced thymoma and DPB, and the others developed DPB at different time points after thymectomy. Previous studies have presented the possible etiologies of bronchiectasis in thymic neoplasms.[ 2 , 3 ] Immune system irregularities related to thymic neoplasms might be the underlying etiology for DPB development. That is, abnormal immune responses could affect the bronchi and respiratory bronchioles. The other two possible etiologies were recurrent respiratory tract infection in patients with Good syndrome and expectoration difficulties in patients with MG. Of the 16 patients, 3 were diagnosed with MG and DPB. One patient developed concomitant MG and DPB upon thymoma diagnosis. The other two patients developed DPB several years after thymectomy. In the case report of Ogoshi et al., the patient presented with recurrent lower respiratory infections 9 months after the thymectomy where neurological abnormalities were not observed. Considering the patient's negative reaction to cold agglutinin, low globulin levels, and reduced B lymphocytes in the blood, there might be the possibility of Good syndrome with bronchopulmonary lesions resembling DPB. Although the B lymphocyte count in the peripheral blood decreased, B lymphocytes surrounded the terminal bronchioles in this case. This phenomenon could be a contributing factor to DPB development in patients with Good syndrome. [8] In this case, DPB developed after MG was effectively treated. In our case, DPB developed before symptoms of MG were present. Expectoration difficulty may have had minimal contribution to the development of DPB. Consequently, immune dysregulation can be the main underlying factor for DPB in patients with a history of thymic neoplasms. In the previous cases, patients diagnosed with thymoma and DPB ( Table 2 ) commonly received macrolide therapy. Two of five patients with Good syndrome received immunoglobulin replacement. In terms of outcomes, 3 of 16 patients eventually died. One patient died of progressive DPB and severe respiratory infection. Table 2 Reported cases of thymoma complicated with diffuse panbronchiolitis Age/sex Country Time to DPB diagnosis MG Time to MG diagnosis Other complications of thymoma Treatment Outcome Reference 69/M Japan 2.5 years after thymectomy - NA Good syndrome Immunoglobulin replacement Death [ 9 ] 58/F Japan Simultaneous - NA Nil Macrolide Death [ 10 ] 58/M Japan Simultaneous - NA Good syndrome Immunoglobulin replacement NA [ 11 ] 15/M China Simultaneous - NA Nil NA NA [ 12 ] 54/M China Simultaneous - NA Nil NA NA [ 12 ] 22/F China Simultaneous - NA Nil Macrolide Improvement [ 13 ] 54/M China Simultaneous - NA Nil Macrolide Improvement [ 13 ] 65/F Japan Simultaneous - NA Good syndrome, pure red cell aplasia Macrolide Improvement [ 14 ] 41/F China 1 year after thymectomy - NA Nil Macrolide Improvement [ 15 ] 70/M China 5 years after thymectomy - NA Nil Macrolide Improvement [ 16 ] 50/M India 6 months after thymectomy - NA Nil Macrolide Improvement [ 17 ] 67/F China 1 year after thymectomy - NA Good syndrome Macrolide Improvement [ 18 ] 69/M Caucasian 1 year after thymectomy - NA Nil Macrolide Improvement [ 19 ] 27/M China Simultaneous + Simultaneous Nil Macrolide Improvement [ 20 ] 45/M Japan 9 moths after thymectomy + Simultaneous Good syndrome, pure red cell aplasia Corticosteroid, cyclosporine, Macrolide Improvement [ 8 ] 58/M Japan 12 years after thymectomy + Simultaneous Alopecia, dysgeusia, myositis Macrolide, corticosteroid Death due to DPB progression and fatal respiratory infection [ 21 ] The clinical features of PTMG were similar to those of prethymectomy MG[ 22 ], and the long-term overall survival was not significantly affected by MG development after thymectomy.[ 23 ] Pyridostigmine is the preferred choice for patients with symptoms and corticosteroids and azathioprine for those who do not sufficiently respond to symptomatic therapy.[ 4 ] However, the therapeutic approach for both MG and DPB presents complex challenges. Macrolide therapy is essential for DPB, and antibiotic quinolones play a key role in treating respiratory tract infections caused by P. aeruginosa in the outpatient department. However, the use of macrolide and quinolone antibiotics both comes with the potential of worsening MG. Aminoglycosides can also exacerbate MG. Contrary to expectations, our case showed that inhaled amikacin might be a safe therapeutic approach for patients with MG who presented with P. aeruginosa -associated lung infection. The treatment of steroid-dependent patients is another challenge. A reduced steroid dose worsens MG symptoms. Meanwhile, an increased dose may exacerbate DPB. To the best of our knowledge, this is the first case report on the sequential development of DPB followed by PTMG. Our case sheds light on the persistent state of immune dysregulation in patients with thymoma, even after thymectomy, with various temporal onsets. DPB diagnosis should be considered in patients exhibiting respiratory symptoms, recurrent respiratory infections, and radiological indications such as diffuse nodules or bronchiectasis. Further studies should be performed to investigate strategies for preventing or reducing immune dysregulation after thymectomy. Abbreviations MG = myasthenia gravis; PTMG = post-thymectomy myasthenia gravis; DPB = diffuse panbronchiolitis; CT = computed tomography Declarations Ethics approval and consent to participate Written informed consent was obtained from the patient. Ethics approval is not applicable to case reports. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Availability of data and materials The data and material that support this case report are available from the corresponding author on reasonable request. Competing interests The authors have no conflicts of interest to declare. Funding Not applicable. Authors' contributions Chun-Ying Chou contributed to the literature search and drafted the manuscript. Min-Shu Hsieh performed the pathological diagnosis, interpreted the pathology, and prepared figure 2. Ping-Hung Kuo provided patient care and significantly contributed to organizing the report, as well as revising the manuscript. All authors have reviewed and approved the final version of the manuscript. Acknowledgements Not applicable. Authors' information (optional) 1 Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S.Rd., Zhongzheng Dist., Taipei 100, Taiwan 2 Department of Pathology, National Taiwan University Hospital, No. 7, Zhongshan S.Rd., Zhongzheng Dist., Taipei 100, Taiwan References Scorsetti M, Leo F, Trama A, D'Angelillo R, Serpico D, Macerelli M, et al. Thymoma and thymic carcinomas. Crit Rev Oncol Hematol. 2016;99:332–50. Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12(9):875–84. Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis — autoantibody characteristics and their implications for therapy. Nat Reviews Neurol. 2016;12(5):259–68. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023–36. Zhou R-Q, Li L-J, Wu Q-C. Refractory post-thymectomy myasthenia gravis with onset at MGFA stage V: a case report. J Cardiothorac Surg. 2022;17(1):115. Liu Y, Xu Y, Tian X, Huang H, Hou X, Chen M, et al. Thymic neoplasms patients complicated with bronchiectasis: Case series in a Chinese hospital and literature review. Thorac Cancer. 2019;10(4):791–8. Poletti V, Casoni G, Chilosi M, Zompatori M. Diffuse panbronchiolitis. Eur Respir J. 2006;28(4):862–71. Ogoshi T, Ishimoto H, Yatera K, Oda K, Akata K, Yamasaki K, et al. A case of Good syndrome with pulmonary lesions similar to diffuse panbronchiolitis. Intern Med. 2012;51(9):1087–91. Chijimatsu Y, Nakazato Y, Homma H, Mizuguchi K. [A case report of Good syndrome complicated by diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1982;20(7):803–8. Okano A, Sato A, Suda T, Suda I, Yasuda K, Iwata M, et al. [A case of diffuse panbronchiolitis complicated by malignant thymoma and Sjögren's syndrome]. Nihon Kyobu Shikkan Gakkai Zasshi. 1991;29(2):263–8. Akai M, Ishizaki T, Sasaki F, Ameshima S, Shigemori K, Higashi T, et al. [Immunodeficiency with thymoma (Good's syndrome) similar to sino-bronchial syndrome]. Nihon Kyobu Shikkan Gakkai Zasshi. 1996;34(7):829–32. Liu H, Liu T, Ren H. [Clinicopathological analysis of 6 cases of diffuse panbronchiolitis]. Zhonghua Bing Li Xue Za Zhi. 2001;30(5):325–7. Xie G, Li L, Liu H, Xu K, Zhu Y. Diffuse panbronchiolitis complicated with thymoma: a report of 2 cases with literature review. Chin Med J (Engl). 2003;116(11):1723–7. Tsuburai T, Ikehara K, Suzuki S, Shinohara T, Mishima W, Tagawa A, et al. [Hypogammaglobulinemia associated with thymoma (Good syndrome) similar to diffuse panbronchiolitis]. Nihon Kokyuki Gakkai Zasshi. 2003;41(6):421–5. Zhang D, Wang CH, Li Q. [Diffuse panbronchiolitis complicated by thymoma: a case report and a review of literature]. Zhonghua Jie He He Hu Xi Za Zhi. 2004;27(9):608–10. Zhai HFHZ, Jiao YM. Diffuse panbronchiolitis occurred after thymectomy for thymoma: A case report. Chin J Respir Crit Care Med. 2009;18:82–3. Jadhav S, Joshi JM. Diffuse panbronchiolitis associated with malignant thymoma. Indian J Chest Dis Allied Sci. 2010;52(1):41–2. Luo T, Wang L, Fu D, Hu R, Kong C, Chen Y, et al. Good's syndrome with diffuse panbronchiolitis as the prominent manifestation: A case and literature review. Respirol Case Rep. 2021;9(12):e0873. Carnevale A, Lucioni E, Daniele MM, Contoli M, Giganti M, Marku B. Diffuse panbronchiolitis as parathymic syndrome in a Caucasian man previously treated for thymoma. Radiol Case Rep. 2021;16(10):3029–33. Jin ZQC, Chen J. Thymoma with diffuse panbronchiolitis-case report. The 12th National Academic Conference on Respiratory Diseases/Chinese Medical Association Annual Meeting on Respiratory Diseases. 2011. Maekawa R, Shibuya H, Hideyama T, Shiio Y. [A case of myasthenia gravis with invasive thymoma associated with diffuse panbronchiolitis, alopecia, dysgeusia, cholangitis and myositis]. Rinsho Shinkeigaku. 2014;54(9):703–8. Rath J, Taborsky M, Moser B, Zulehner G, Weng R, Krenn M, et al. Short-term and sustained clinical response following thymectomy in patients with myasthenia gravis. Eur J Neurol. 2022;29(8):2453–62. Zhang X, Li B, Zou J, Su C, Zhu H, Chen T, et al. Perioperative risk factors for occurrence of myasthenia gravis after thymectomy in patients with thymoma. Interact Cardiovasc Thorac Surg. 2020;31(4):519–26. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4014771","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":278490878,"identity":"6c8137da-5947-4db9-aec2-d1408b685e10","order_by":0,"name":"Chun-Ying Chou","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chun-Ying","middleName":"","lastName":"Chou","suffix":""},{"id":278490879,"identity":"b2c593ea-e89f-4d87-8174-c8dfe2865f9e","order_by":1,"name":"Min-Shu Hsieh","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Min-Shu","middleName":"","lastName":"Hsieh","suffix":""},{"id":278490880,"identity":"c0f3ec96-f87b-401b-a989-b6df7dc9d88e","order_by":2,"name":"Ping-Hung Kuo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACCQYe9h8JFTZAJg/xWhgkHpxJA1JQLQR1grRIPmw7TIIWydm9BwwS2M7n2UvkHmD8UnGYwV4iAb8WaZlzCQkJPLeLeSTyEphlzgCtI6RFTiLH4ECCxO3EHiCDWbIN6ClpwloMGxIMzpGgRVoix5ghIeEAWAvjxzYbwlok55wxY0g4kJzYc+aNwWGGMzY8PPcf4NcicbvHjPHnP7vE9vYcw4c/KiTk2HsO4NcCjBgEOMxDVBpA1sL4g7D6UTAKRsEoGIEAADXwPc3R0rk4AAAAAElFTkSuQmCC","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ping-Hung","middleName":"","lastName":"Kuo","suffix":""}],"badges":[],"createdAt":"2024-03-05 01:34:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4014771/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4014771/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52623274,"identity":"90192f3b-b68e-4492-8f71-6347650a1ad3","added_by":"auto","created_at":"2024-03-13 17:19:20","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2124088,"visible":true,"origin":"","legend":"\u003cp\u003eAxial and coronal views of chest computed tomography scan. \u003cstrong\u003ea, b, c\u003c/strong\u003e At 15 months before this presentation. \u003cstrong\u003ed, e, f \u003c/strong\u003eAt the time of admission for video-assisted thoracoscopic surgery (VATS) biopsy.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4014771/v1/6709359e280b65743d98c2d4.jpg"},{"id":52623275,"identity":"cdee022c-569f-48c7-9b8d-2ce50663dcd5","added_by":"auto","created_at":"2024-03-13 17:19:20","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":7844983,"visible":true,"origin":"","legend":"\u003cp\u003eVideo-assisted thoracoscopic surgery (VATS) lung biopsy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Bronchiolocentric inflammation involving the bronchioles and respiratory bronchioles. (hematoxylin and eosin stain, ×4). \u003cstrong\u003eb\u003c/strong\u003e Inflammatory infiltrates including lymphocytes, plasma cells, and foamy histiocytes (arrow) in the alveolar spaces and interstitium. (hematoxylin and eosin stain, ×10). \u003cstrong\u003ec\u003c/strong\u003e Aggregation of foamy histiocytes in the alveolar spaces and interstitium. (hematoxylin and eosin stain, ×40)\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4014771/v1/624b80b4fe82e530c5893979.jpg"},{"id":52623273,"identity":"80e3ba40-e425-4fe5-b15f-9f3d5b107f8a","added_by":"auto","created_at":"2024-03-13 17:19:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":24300,"visible":true,"origin":"","legend":"\u003cp\u003eClinical course (AE: acute exacerbation)\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4014771/v1/88126c55e686ce89e570090a.png"},{"id":52624152,"identity":"95d44481-062d-4897-8b99-26b9c8ae2d78","added_by":"auto","created_at":"2024-03-13 17:27:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":822559,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4014771/v1/7120c6a7-793a-4608-9ab3-fcee7243e27a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eThymomas and thymic carcinomas are rare primary tumors located in the mediastinum, and derived from the thymic epithelium. Myasthenia gravis (MG) is the most prevalent type of paraneoplastic syndrome associated with these tumors.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Approximately 30% of patients with thymoma either present with or develop MG.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Thymectomy should be performed as an oncological intervention if a thymoma is identified or strongly suspected to prevent local compression and possible spread to the thoracic cavity.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Nevertheless, after thymectomy, patients can develop post-thymectomy myasthenia gravis (PTMG). PTMG refers to the subsequent development of MG after radical surgical resection in patients with thymoma who did not exhibit any signs of MG before surgery. PTMG might be misdiagnosed not only because of its rare incidence, which has been reported to be between 0.97% and 13.39% in previous studies, but also due to the uncertain interval between the removal of thymoma and the new onset of PTMG, which can range from 3 days to over 14 years.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBronchiectasis has been recognized as a potential complication associated with thymic neoplasms, and there have been reports of diffuse panbronchiolitis (DPB) occurring in conjunction with these neoplasms as well. Both bronchiectasis and DPB are potentially raised from an aberrant immune response involving lymphocytes.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Based on what we know, there have been only three reported cases of concurrent MG and DPB. Notably, MG was diagnosed simultaneously with thymoma in all three cases.\u003c/p\u003e \u003cp\u003eHerein, we present a patient who developed DPB and PTMG sequentially several years after thymectomy.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 45-year-old Taiwanese woman who had a productive cough for 1.5 years, presented at our hospital. The patient also complained of symptoms such as rhinorrhea, anosmia, intermittent ear fullness, shortness of breath, and an 18% weight loss within half a year. She had no fever, chest pain, hemoptysis, or night sweating. She never smoked. Further, she had undergone robot-assisted thymectomy, along with lymph node dissection, for B2-type thymoma 7 years back. After surgery, she received adjuvant radiotherapy targeting the tumor bed in the anterior mediastinum. The cumulative dose administered was 5,400 cGy divided into 30 fractions. Chest computed tomography (CT) scan was conducted every 6 months after surgery. The anterior mediastinum presented with postoperative changes. Further, the medial aspect of the left upper lobe presented with post-irradiation changes and subpleural fibrosis. However, 6 years after the surgery, subsequent follow-up chest CT scans revealed increased diffuse bronchitis and bronchiolitis over both lungs \u003cstrong\u003e(\u003c/strong\u003eFig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea, b, c\u003cstrong\u003e)\u003c/strong\u003e, without evidence of recurrent thymoma. The patient also presented with rhinorrhea, anosmia and ear fullness. Thus, she was referred to the otolaryngologist\u0026rsquo;s outpatient clinic for further evaluation. Sinus CT scan imaging and local findings confirmed the diagnosis of chronic bilateral pansinusitis and chronic left otitis media. She was prescribed with short-course therapy of oral clarithromycin at a dosage of 500 mg/day and nasal irrigation was recommended. However, despite these interventions, the symptoms persisted intermittently and did not completely resolve.\u003c/p\u003e\n\u003cp\u003eThe patient was admitted to the ward for further evaluation of the underlying etiology. Physical examination revealed coarse breathing sounds with inspiratory crackles. Chest CT scan revealed diffuse bronchial wall thickening and mild bronchiectasis with multiple centrilobular nodules, ground-glass nodules, and air trapping \u003cstrong\u003e(\u003c/strong\u003eFig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed, e, f\u003cstrong\u003e)\u003c/strong\u003e. The pulmonary function test showed that the ratio of the forced expiratory volume in 1 s to forced vital capacity was 77.6%. The forced vital capacity (FVC) was 1.61 L, which was 53.1% of the predicted value. This finding indicated mixed obstructive and restrictive ventilatory defect. Anti-neutrophil cytoplasmic antibodies, the level of serum total immunoglobulin-E, and blood eosinophil counts were checked to identify the underlying etiologies of sinopulmonary syndrome and was found to be within the normal range. Serum immunoglobulin tests also showed no signs of hypogammaglobulinemia. Bronchial alveolar lavage showed no evidence of fungal or Mycobacterial infection. To investigate the underlying etiologies, video-assisted thoracoscopic surgery (VATS) lung biopsy was conducted. The pathological biopsy report confirmed the DPB diagnosis \u003cstrong\u003e(\u003c/strong\u003eFig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e. After DPB diagnosis, azithromycin at a dose of 500 mg/day was prescribed. In the event of worsening symptoms, the patient received short-term treatment with amikacin inhalation. Moreover, oral levofloxacin was due to the presence of \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e in the previous sputum culture. The patient presented with significant improvement in symptoms including productive cough.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNevertheless, 3 months after DPB diagnosis, the patient experienced a gradual onset of symptoms, which included facial weakness, head drop, diplopia, and proximal muscle weakness. Subsequently, she had ptosis with diurnal fluctuations and dysphagia. Arterial blood gas analysis revealed hypercapnia with a partial carbon dioxide pressure of 78.6 mmHg, a bicarbonate level of 39.9 mmol/l, and a pH of 7.32. Noninvasive positive pressure ventilation support was administered. The pulmonary function test revealed deteriorated FVC \u003cstrong\u003e(\u003c/strong\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e. Due to the aforementioned symptoms, the acetylcholine receptor antibody test was conducted. Results revealed a high level of acetylcholine receptor antibody at 7.616 nmol/l, which is significantly above the normal range (\u0026lt;\u0026thinsp;0.2 nmol/l). The repetitive stimulation test also showed a decremental change in the resting and postexercise test results. These findings indicated an abnormality at the neuromuscular junction. Thus, the patient was diagnosed with MG \u003cstrong\u003e(\u003c/strong\u003eFig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDiagnostic timeline and serial respiratory function test results.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMonth (M)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVATS biopsy\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e3 M (MG)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e4 M\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e8 M\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e10 M\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFVC (% predicted)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePImax/Pemax (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026minus;81/+107\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026minus;52/+50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026minus;88/+92\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTreatment with prednisolone at a daily dose of 0.5 mg/kg and pyridostigmine bromide at a dose of 60 mg four times a day was initiated. Thereafter, ptosis resolved and proximal weakness improved. Consequently, the patient was gradually weaned off noninvasive positive pressure ventilation support. The patient was dependent on prednisolone at a dose of 30 mg on alternate days. She reported worsened weakness at the lower dosage. Azithromycin regimen was administered daily for DPB, and intermittent short-course levofloxacin was administered if purulent sputum was noted. However, after several months later, the patient was readmitted because of another episode of \u003cem\u003eP. aeruginosa\u003c/em\u003e-related respiratory infection complicated by desaturation. She received intravenous antibiotics to manage the infection. After successfully controlling the infection, the patient has achieved a stable condition and is receiving long-term maintenance therapies, with pyridostigmine, corticosteroids, azithromycin, and inhaled amikacin.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eIn this report, we describe a case who develops DPB and PTMG sequentially several years after thymectomy for thymoma. We presented a complex clinical course and diagnostic challenge, and under careful clinical assessment, the patient was diagnosed and treated correctly and appropriately in a timely manner.\u003c/p\u003e \u003cp\u003eDPB typically manifests between the ages of 20 and 50, with a higher prevalence in males compared to females. This disease primarily affects individuals in Asian populations. Certain HLA types have been found to be associated with the disease.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Greater than 80% of patients with DPB have a history of chronic paranasal sinusitis, or they continuously present with the condition.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] In the current case, the patient was initially diagnosed with sinusitis, which exhibited features consistent with those described in the literature.\u003c/p\u003e \u003cp\u003eTo assess the association between thymoma and DPB, we evaluated the data of 16 patients from reports published in PubMed, Medline, and Web of Science, using the terms \u0026ldquo;diffuse panbronchiolitis\u0026rdquo; and \u0026ldquo;thymoma\u0026rdquo; or \u0026ldquo;thymic carcinoma\u0026rdquo; \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Eight patients concomitantly experienced thymoma and DPB, and the others developed DPB at different time points after thymectomy.\u003c/p\u003e \u003cp\u003ePrevious studies have presented the possible etiologies of bronchiectasis in thymic neoplasms.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Immune system irregularities related to thymic neoplasms might be the underlying etiology for DPB development. That is, abnormal immune responses could affect the bronchi and respiratory bronchioles. The other two possible etiologies were recurrent respiratory tract infection in patients with Good syndrome and expectoration difficulties in patients with MG.\u003c/p\u003e \u003cp\u003eOf the 16 patients, 3 were diagnosed with MG and DPB. One patient developed concomitant MG and DPB upon thymoma diagnosis. The other two patients developed DPB several years after thymectomy. In the case report of Ogoshi et al., the patient presented with recurrent lower respiratory infections 9 months after the thymectomy where neurological abnormalities were not observed. Considering the patient's negative reaction to cold agglutinin, low globulin levels, and reduced B lymphocytes in the blood, there might be the possibility of Good syndrome with bronchopulmonary lesions resembling DPB. Although the B lymphocyte count in the peripheral blood decreased, B lymphocytes surrounded the terminal bronchioles in this case. This phenomenon could be a contributing factor to DPB development in patients with Good syndrome.\u003csup\u003e[8]\u003c/sup\u003e In this case, DPB developed after MG was effectively treated. In our case, DPB developed before symptoms of MG were present. Expectoration difficulty may have had minimal contribution to the development of DPB. Consequently, immune dysregulation can be the main underlying factor for DPB in patients with a history of thymic neoplasms.\u003c/p\u003e \u003cp\u003eIn the previous cases, patients diagnosed with thymoma and DPB \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e commonly received macrolide therapy. Two of five patients with Good syndrome received immunoglobulin replacement. In terms of outcomes, 3 of 16 patients eventually died. One patient died of progressive DPB and severe respiratory infection.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReported cases of thymoma complicated with diffuse panbronchiolitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge/sex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime to DPB diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTime to MG diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOther complications\u003c/p\u003e \u003cp\u003eof thymoma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e69/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5 years after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGood syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImmunoglobulin replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e58/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e58/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGood syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImmunoglobulin replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e54/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e54/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGood syndrome, pure red cell aplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 year after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 years after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 months after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e67/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 year after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGood syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e69/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaucasian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 year after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 moths after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGood syndrome, pure red cell aplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCorticosteroid, cyclosporine, Macrolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eImprovement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e58/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 years after thymectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSimultaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlopecia, dysgeusia, myositis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMacrolide,\u003c/p\u003e \u003cp\u003ecorticosteroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDeath due to DPB progression and fatal respiratory infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe clinical features of PTMG were similar to those of prethymectomy MG[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and the long-term overall survival was not significantly affected by MG development after thymectomy.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Pyridostigmine is the preferred choice for patients with symptoms and corticosteroids and azathioprine for those who do not sufficiently respond to symptomatic therapy.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eHowever, the therapeutic approach for both MG and DPB presents complex challenges. Macrolide therapy is essential for DPB, and antibiotic quinolones play a key role in treating respiratory tract infections caused by \u003cem\u003eP. aeruginosa\u003c/em\u003e in the outpatient department. However, the use of macrolide and quinolone antibiotics both comes with the potential of worsening MG. Aminoglycosides can also exacerbate MG. Contrary to expectations, our case showed that inhaled amikacin might be a safe therapeutic approach for patients with MG who presented with \u003cem\u003eP. aeruginosa\u003c/em\u003e-associated lung infection. The treatment of steroid-dependent patients is another challenge. A reduced steroid dose worsens MG symptoms. Meanwhile, an increased dose may exacerbate DPB.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, this is the first case report on the sequential development of DPB followed by PTMG. Our case sheds light on the persistent state of immune dysregulation in patients with thymoma, even after thymectomy, with various temporal onsets. DPB diagnosis should be considered in patients exhibiting respiratory symptoms, recurrent respiratory infections, and radiological indications such as diffuse nodules or bronchiectasis. Further studies should be performed to investigate strategies for preventing or reducing immune dysregulation after thymectomy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMG = myasthenia gravis; PTMG = post-thymectomy myasthenia gravis; DPB = diffuse panbronchiolitis; CT = computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient. Ethics approval is\u003c/p\u003e\n\u003cp\u003enot applicable to case reports.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of\u003c/p\u003e\n\u003cp\u003ethis case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and material that support this case report are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChun-Ying Chou contributed to the literature search and drafted the manuscript. Min-Shu Hsieh performed the pathological diagnosis, interpreted the pathology, and prepared figure 2. Ping-Hung Kuo provided patient care and significantly contributed to organizing the report, as well as revising the manuscript. All authors have reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S.Rd., Zhongzheng Dist., Taipei 100, Taiwan\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Pathology, National Taiwan University Hospital, No. 7, Zhongshan S.Rd., Zhongzheng Dist., Taipei 100, Taiwan\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eScorsetti M, Leo F, Trama A, D'Angelillo R, Serpico D, Macerelli M, et al. Thymoma and thymic carcinomas. Crit Rev Oncol Hematol. 2016;99:332\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Str\u0026ouml;bel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12(9):875\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis \u0026mdash; autoantibody characteristics and their implications for therapy. Nat Reviews Neurol. 2016;12(5):259\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou R-Q, Li L-J, Wu Q-C. Refractory post-thymectomy myasthenia gravis with onset at MGFA stage V: a case report. J Cardiothorac Surg. 2022;17(1):115.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Xu Y, Tian X, Huang H, Hou X, Chen M, et al. Thymic neoplasms patients complicated with bronchiectasis: Case series in a Chinese hospital and literature review. Thorac Cancer. 2019;10(4):791\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoletti V, Casoni G, Chilosi M, Zompatori M. Diffuse panbronchiolitis. Eur Respir J. 2006;28(4):862\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgoshi T, Ishimoto H, Yatera K, Oda K, Akata K, Yamasaki K, et al. A case of Good syndrome with pulmonary lesions similar to diffuse panbronchiolitis. Intern Med. 2012;51(9):1087\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChijimatsu Y, Nakazato Y, Homma H, Mizuguchi K. [A case report of Good syndrome complicated by diffuse panbronchiolitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1982;20(7):803\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkano A, Sato A, Suda T, Suda I, Yasuda K, Iwata M, et al. [A case of diffuse panbronchiolitis complicated by malignant thymoma and Sj\u0026ouml;gren's syndrome]. Nihon Kyobu Shikkan Gakkai Zasshi. 1991;29(2):263\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkai M, Ishizaki T, Sasaki F, Ameshima S, Shigemori K, Higashi T, et al. [Immunodeficiency with thymoma (Good's syndrome) similar to sino-bronchial syndrome]. Nihon Kyobu Shikkan Gakkai Zasshi. 1996;34(7):829\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu H, Liu T, Ren H. [Clinicopathological analysis of 6 cases of diffuse panbronchiolitis]. Zhonghua Bing Li Xue Za Zhi. 2001;30(5):325\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie G, Li L, Liu H, Xu K, Zhu Y. Diffuse panbronchiolitis complicated with thymoma: a report of 2 cases with literature review. Chin Med J (Engl). 2003;116(11):1723\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsuburai T, Ikehara K, Suzuki S, Shinohara T, Mishima W, Tagawa A, et al. [Hypogammaglobulinemia associated with thymoma (Good syndrome) similar to diffuse panbronchiolitis]. Nihon Kokyuki Gakkai Zasshi. 2003;41(6):421\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang D, Wang CH, Li Q. [Diffuse panbronchiolitis complicated by thymoma: a case report and a review of literature]. Zhonghua Jie He He Hu Xi Za Zhi. 2004;27(9):608\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhai HFHZ, Jiao YM. Diffuse panbronchiolitis occurred after thymectomy for thymoma: A case report. Chin J Respir Crit Care Med. 2009;18:82\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJadhav S, Joshi JM. Diffuse panbronchiolitis associated with malignant thymoma. Indian J Chest Dis Allied Sci. 2010;52(1):41\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo T, Wang L, Fu D, Hu R, Kong C, Chen Y, et al. Good's syndrome with diffuse panbronchiolitis as the prominent manifestation: A case and literature review. Respirol Case Rep. 2021;9(12):e0873.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarnevale A, Lucioni E, Daniele MM, Contoli M, Giganti M, Marku B. Diffuse panbronchiolitis as parathymic syndrome in a Caucasian man previously treated for thymoma. Radiol Case Rep. 2021;16(10):3029\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJin ZQC, Chen J. Thymoma with diffuse panbronchiolitis-case report. The 12th National Academic Conference on Respiratory Diseases/Chinese Medical Association Annual Meeting on Respiratory Diseases. 2011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaekawa R, Shibuya H, Hideyama T, Shiio Y. [A case of myasthenia gravis with invasive thymoma associated with diffuse panbronchiolitis, alopecia, dysgeusia, cholangitis and myositis]. Rinsho Shinkeigaku. 2014;54(9):703\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRath J, Taborsky M, Moser B, Zulehner G, Weng R, Krenn M, et al. Short-term and sustained clinical response following thymectomy in patients with myasthenia gravis. Eur J Neurol. 2022;29(8):2453\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang X, Li B, Zou J, Su C, Zhu H, Chen T, et al. Perioperative risk factors for occurrence of myasthenia gravis after thymectomy in patients with thymoma. Interact Cardiovasc Thorac Surg. 2020;31(4):519\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diffuse panbronchiolitis, Myasthenia gravis, Thymoma, Thymic neoplasm, Case report","lastPublishedDoi":"10.21203/rs.3.rs-4014771/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4014771/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMyasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. To our knowledge, only three cases of combined MG and DPB have been reported.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. The patient had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Physical examination revealed coarse breathing sounds with inspiratory crackles. Chest computed tomography scan revealed progressive diffuse bronchitis and bronchiolitis. DPB was confirmed on video-assisted thoracoscopic surgery lung biopsy, and sputum culture showed the presence of \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. The patient\u0026rsquo;s respiratory symptoms improved after treatment with oral azithromycin, levofloxacin, and the transient use of inhaled amikacin. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia, with an arterial partial pressure of carbon dioxide measuring 78.6 mmHg, requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Muscle weakness responded to pyridostigmine and corticosteroids. However, she was readmitted after several months because of another episode of \u003cem\u003eP. aeruginosa-related\u003c/em\u003e respiratory infection. Currently, she is in stable condition with long-term maintenance therapies comprising pyridostigmine, corticosteroid, azithromycin, and inhaled amikacin.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTo best of our knowledge, this might be the first case of sequential development of DPB followed by PTMG. The coexistence of DPB and PTMG poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapy for MG.\u003c/p\u003e","manuscriptTitle":"Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-13 17:19:15","doi":"10.21203/rs.3.rs-4014771/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-19T14:25:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-17T16:50:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-13T17:08:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7b56dfd9-f241-4831-8399-e1b422c4f8f6","date":"2024-04-09T16:48:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4ae3c871-8ae0-41cd-b588-83028d737d7d","date":"2024-04-09T14:38:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-09T13:07:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-08T18:13:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-11T22:33:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-11T22:30:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2024-03-05T01:21:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b69ba701-c713-4f40-9761-029d0d917be2","owner":[],"postedDate":"March 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-06-26T06:36:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-13 17:19:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4014771","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4014771","identity":"rs-4014771","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}