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Risk Factors and Treatment of Pneumothorax Secondary to Granulomatosis with Polyangiitis: a Clinical Analysis of 25 Cases Xuhua Shi, Yongfeng Zhang and Yuewu Lu*

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Risk Factors and Treatment of Pneumothorax Secondary to Granulomatosis with Polyangiitis: a Clinical Analysis of 25 Cases Xuhua Shi, Yongfeng Zhang and Yuewu Lu* Shi et al. Journal of Cardiothoracic Surgery (2018) 13:7 DOI 10.1186/s13019-018-0695-8 REVIEW Open Access Risk factors and treatment of pneumothorax secondary to granulomatosis with polyangiitis: a clinical analysis of 25 cases Xuhua Shi, Yongfeng Zhang and Yuewu Lu* Abstract Objectives: To investigate the risk factors and treatment strategies for pneumothorax secondary to granulomatosis with polyangiitis (GPA). Method: Retrospective analysis of cases with pneumothorax secondary to GPA from our own practice and published on literature. Results: A total of 25 patients, 18 males and 7 females, mean age 44 ± 15.7 years, were analyzed. Diagnosis included pneumothorax (11 cases), hydropneumothorax (n = 5), empyema (n = 8) and hemopneumothorax (n = 1). 88% (22/25) patients showed single/multiple pulmonary/ subpleural nodules with/without cavitation on chest imaging. Erythrocyte sedimentation rate and C-reactive protein were both elevated. Corticosteroids and immunosuppressive agents were used in 16 cases. Five cases received steroid pulse therapy, of which 4 patients survived. Pleural drainage was effective in some patients. Seven patients underwent surgical operations. In the 10 fatal cases, infection and respiratory failure were the most common cause. Lung biopsy/ autopsy showed lung/pleural necrotizing granulomatous vasculitis, breaking into the chest cavity, pleural fibrosis, bronchial pleural fistula, etc. The mean age in the death group was greater than the survival group (53 ± 12.9 years vs 40.1 ± 14.7 years, p = 0.05), the ineffective pleural drainage was also higher in the death group (5/5 vs 0/7, p =0.01). Conclusions: Pneumothorax was seen in the active GPA, due to a variety of reasons, and gave rise to high fatality rate. Aggressive treatment of GPA can improve the prognosis. Older and lack of response for pleural drainage indicates poor prognosis. Keywords: Granulomatosis with Polyangiitis, Wegener’s granulomatosis, Pneumothorax Background complication, when occurred, can be categorized into Granulomatosis with polyangiitis (GPA), also known as pneumothorax, hydropneumothorax, empyema, hemop- Wegener’s granulomatosis, is a necrotizing granulomatous neumothorax, etc [3, 4]. So far there were only 20 cases of vasculitis, most commonly involving lung (Fig. 1), upper pneumothorax reported and the clinical presentation var- respiratory tract, and kidney [1]. When the respiratory sys- ied. Also, the cause and risk factors of GPA associated tem is involved, lung imaging study usually shows nod- pneumothorax are unclear, and there is no consensus on ules, infiltrates, alveolar hemorrhage [2]. When pleural is important aspects of treatment strategy, such as, when the involved, the patient can present with pleurisy, pleural ef- pneumothorax or infection is developed, how should fusion and thickening. Pneumothorax is a rare but serious treatment for the primary disease be adjusted? How to ap- propriately apply the pleural drainage and other surgical interventions? We encountered one case of GPA associ- * Correspondence: [email protected]; [email protected] Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, ated hydropneumothorax in our clinic who recovered Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, after undergone active treatment of the primary disease Beijing 100020, China © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. Shi et al. Journal of Cardiothoracic Surgery (2018) 13:7 Page 2 of 7 granulomatosis confirmed by clinical and pathology exam- ination, but only had 1 case complicated by pneumo- thorax. We carefully reviewed and collected information on each patient’s clinical diagnoses, gender, age, time from disease onset to the development of pneumo- thorax, diagnosis of pneumothorax, the type of pneumo- thorax (pneumothorax, hydropneumothorax, empyema, hemopneumothorax), clinical presentations, laboratory test results (including anti-neutrophil cytoplasmic antibodies, anti-PR3 antibody, erythrocyte sedimentation rate, C- reactive protein), lung imaging findings (X ray / CT), corti- costeroids and immunosuppressants treatment, pleural drainage, surgery, infection (infection site, pathogens, etc.), biopsy / autopsy pathology results. Four cases were re- ported from non-English literature, for which the informa- Fig. 1 The microscopic features of pulmonary nodule obtained by percutaneous lung biopsy in a patient with granulomatous vasculitis tion was gathered from the abstract written in English. (GPA). There are more infiltrating lymphocytes, neutrophils and Case analysis included general patient characteristics eosinophils in fibrous tissues. Granulomas composed of tissue cells (gender, age, duration of disease, type of pneumothorax, and inflammatory cells are also visible. There are prominent lung imaging findings, extrapulmonary manifestations, inflammatory cell infiltration and granuloma in the wall of small laboratory results, treatment and prognosis), infection vessels. HE staining, 100× (infection site, pathogens, etc.), biopsy / autopsy pathology results (lungs and other organs), as well as comparison be- and pleural drainage. The incidence of GPA associated tween death and survived patients. This analysis included pneumothorax is low. However, if not treated properly the patients who met the 1990 American College of Rheuma- fatality rate can be quite high. Currently there is still no tology (ACR) classification criteria for Wegener’sgranulo- cohort-based research. Therefore, we conducted a retro- matosis [1, 25] defined as follows: 1) Nasal or oral spective analysis of our case and all cases reported in the inflammation: development of painful or painless oral ul- literature [4–24], aiming to identify the risk factors of cers or purulent or bloody nasal discharge; 2) Abnormal GPA associated pneumothorax and explore the important chest radiograph: chest radiograph showing the presence principles of its clinical management once occurred, to of nodules, fixed infiltrates, or cavities; 3) Urinary sedi- guide the optimal treatment of the patients. ment: microhematuria (>5 red blood cells per high power field) or red cell casts in urine sediment; 4) Granuloma- Materials and methods tous inflammation on biopsy: histologic changes showing Because it is a retrospective research, the period of observa- granulomatous inflammation within the wall of an artery tion spans from 1978 (the first case) to 2015 (the last case). or in the perivascular or extravascular area (artery or ar- The patients came from two sources. The first was the case teriole). Patients need to meet at least 2 criteria to be diag- diagnosed and treated in our clinic. The second source in- nosed as Wegener’s granulomatosis. The cases diagnosed cluded cases reported in the literature identified from the before 1990 were confirmed with biopsy showing necro- search of major databases, including: Chinese Biomedical tizing granulomatous vasculitis. Literature Database (CBM), Pubmed, EMBASE, and BIO- SIS Preview. The searching key words were “pneumo- Statistical analysis thorax”, “multi-vessel granulomatous inflammation” and The general characteristics of the patients were summa- “Wegener’sgranulomatosis.” Full text articles were re- rized with descriptive statistics. Age, duration, anti-PR3, trieved for review. All procedures performed in studies in- erythrocyte sedimentation rate (ESR) and C-reactive volving human participants were in accordance with the protein (CRP) were expressed as mean ± standard devi- ethical standards of the institutional and/or national re- ation, and were compared between death group and search committee and with the 1964 Helsinki declaration survival group using independent t-test. Categorical vari- and its later amendments or comparable ethical standards. ables, including sex, types of pneumothorax, chest imaging Given the small number of reported cases and wide (nodules, cavity, pulmonary hemorrhage), extrapulmonary time span covered by the search, we went over the manifestations (fever, skin lesions, nasal and sinus involve- papers carefully, excluded the cases of pneumothorax ment, oral ulcers, renal involvement, nervous system in- unrelated to GPA (for example, pneumothorax caused volvement, arthralgia / arthritis, parotid swelling), positived by lung biopsy during the disease diagnosis). One ANCA, pleural drainage, surgery, spontaneous absorption, lung imaging study included 31 cases of Wegener’s death, infection site, pathogens, biopsy site and pathology, Shi et al. Journal of Cardiothoracic Surgery (2018) 13:7 Page 3 of 7 therapy and interruption of treatment, risk factors for Table 1 General characteristics of patients with pneumothorax pneumothorax secondary to GPA, were summarized as secondary to GPA percentage, and were analyzed between death group and Clinical features Results survival group using chi-square test. Male/Female (case) 18(72%)/7(28%) Age(year) 44 ± 15.7(16~70) Results Duration (weeks) 26 ± 51.0(0.83~216)
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