Recurrent pleural effusion secondary to endometriosis: a rare malady

Thoracic endometriosis is a rare entity, wherein thoracic endometrial tissue deposition occurs. Recurrent pleural effusion is one of its manifestations. Diagnosis and treatment are often challenging, owing to the rarity of the condition and recurrences. We present an interesting case of a young woman of childbearing age who presented with recurrent haemorrhagic pleural effusion. She was referred to our centre after her initial video-assisted thoracoscopic biopsy was inconclusive. She was re-evaluated, and video-assisted thoracoscopic biopsy confirmed thoracic endometriosis. She underwent pleurodesis two times and currently on hormonal treatment, maintaining well.

obstetrics, gynaecology and fertility, respiratory system

Endometriosis is a clinical condition characterised by functional endometrial tissue deposition at various sites outside its site of origin. Different areas include the abdominopelvic cavity, ovaries, uterosacral ligaments, fallopian tubes, the pouch of Douglas, gastrointestinal tract, urinary tract and thorax. Comparatively, thoracic involvement is a rare presentation.1 When endometrial tissue deposits in the thoracic cavity, it is known as thoracic endometriosis (TE). Various manifestations of TE include catamenial pneumothorax, catamenial haemothorax, haemoptysis and lung nodules in decreasing order of frequency.2 Here, we describe a rare case of right-sided recurrent pleural effusion secondary to TE. Case presentation A 30-year-old woman with a history of hyperthyroidism presented with dyspnoea and productive cough with white sputum ongoing for 6 months. A review of symptoms did not reveal any haemoptysis, fever, chest pain, weight loss or chest trauma. She was nulliparous with a background of primary infertility. She was married for 7 years and was trying to conceive without success. There was no history of previous miscarriages or history of undergoing any uterine procedures. Menstrual history was unremarkable other than a history of dysmenorrhoea. Family history was unremarkable. She presented with these reports to a local hospital, diagnosed to have pleural effusion and an intercostal tube was inserted, and the fluid was drained. She underwent a thoracoscopic biopsy, which showed pleurisy with no evidence of granulomas/malignancy. A review of the biopsy from a different centre was inconclusive. She was empirically started on antitubercular drugs, as tuberculosis was endemic in the region. The intercostal tube was removed after a week. However, her symptoms persisted, and she was later referred to the pulmonary medicine department of our centre. On examination, vitals were stable. Respiratory system examination revealed stony dull notes on percussion and absent breath sounds in the right middle and lower lung fields, consistent with right-sided pleural effusion. Investigations Blood workup was unremarkable except for anaemia. Chest X-ray was suggestive of moderate right-sided pleural effusion (figure 1). CT thorax showed collapse consolidation of right middle and lower lobes with air bronchograms in situ, along with right-sided hydropneumothorax, probably secondary to disease process complicated by the previous intervention. There was no significant mediastinal shift or mediastinal lymph nodes. The pleural fluid analysis showed exudative effusion (pleural fluid protein: 3.7 g/dL, serum protein: 6.5 g/dL, lacatate dehydrogenase (LDH)—74.1U/L, haematocrit-1%, total count—86 cells/cu.mm, lymphocyte (78%) predominant). Pleural fluid adenosine deaminase (ADA) was 11 IU/L(laboratory reference limit 0–24 IU/L). Cytology was negative for malignant cells. It was a haemorrhagic pleural effusion, though not a true haemothorax. Video-assisted thoracoscopy was done, which revealed collapsed right lung with multiple adhesions (figure 2) and few parietal pleural nodules with discolouration. Adhesiolysis was done, and biopsy was taken from parietal pleural nodules (figure 3). Histopathology of biopsy from nodules showed pleural endometriosis (figure 4). Treatment Chest tube insertion was done following thoracoscopy, and fluid was found to be haemorrhagic. The patient was started on hormonal therapy with dienogest, a progestin medication. Once the drain fluid amount was <100 mL/day and the lung had expanded, pleurodesis was done with 60 units of bleomycin. Bleomycin was chosen based on availability, favourable cost and local expertise. The intercostal drain was removed after 2 weeks, as the drain amount reduced. She responded well to treatment and was discharged. After 6 months of treatment, dienogest was stopped as the patient wanted to conceive. However, after 2 weeks of stopping dienogest, she returned to the hospital with similar reports, and on examination, she was found to have a recurrent right-sided effusion. An intercostal tube was again inserted and fluid drained. After ruling out secondary causes, she was restarted on hormonal therapy with dienogest. Pleurodesis was repeated with doxycycline, as earlier pleurodesis with bleomycin was not successful. The intercostal tube removed after 4 days, and the patient was discharged. Outcome and follow-up The patient is under regular follow-up monthly for the next 6 months and is doing well.

TE syndrome (TES) is a relatively rare disorder. It is marked by the presence of endometrial stroma and glandular deposits in the thoracic cavity, commonly associated with the visceral or parietal pleura, parenchyma of lungs or airways.2 Various manifestations of TE include catamenial pneumothorax (72%–73%), catamenial haemothorax (12%–14%), haemoptysis (7%–12%) and lung nodules (2%–6%).3 4 The majority of TES cases occur in the right haemithorax (92%), followed by the left haemithorax (5%), and the least common is bilateral (3%) involvement.5 Right preferentiality has been linked to the favoured flow of peritoneal fluids through the right paracolic gutter to the right subphrenic space.6 Our patient fell within the reproductive age group and presented with right-sided involvement multiple times. Clinical symptoms are variable and depend on the site of endometrial tissue deposits. These may include cough, chest pain, shoulder pain and shortness of breath.7 Our patient had presented with cough and shortness of breath, with a background dysmenorrhea history. The exact pathogenesis of TE remains unclear. Proposed theories include translocation of endometrial tissue and its autotransplantation into the thoracic cavity via defects in the diaphragm and fallopian tubes, dissemination through the venous or lymphatic network and mesothelial cell metaplasia of the pleural surface. However, all the TES clinical manifestations cannot be accounted for by the above postulates, and multifaceted aetiology must be considered.7 Diagnosis of TE is arduous and often delayed, leading to recurrent hospitalisations.8 Cyclical recurrence of symptoms in relation to menstruation and right-sided predominance in young women in the reproductive age group may point towards TE.8 Imaging modalities, although not specific, are the first-line methods. Chest X-ray may show pneumothorax, pleural effusion and pulmonary nodules. Contrast-enhanced CT (CECT) is not very specific and is commonly used to rule out other diseases.8 It may reveal suggestive findings like defects in the diaphragm or nodularities on pleural and diaphragmatic surfaces.9 As endometrial deposits tend to lie peripherally in the lungs, bronchoscopy has a limited diagnostic role.8 The gold standard for diagnosis for TE remains video-assisted thoracoscopic surgery (VATS), as it allows direct visualisation of intrathoracic structures and can be therapeutic as well.10 Diaphragmatic defect closure, pleurodesis-mechanical or chemical and resection of the lung can be achieved with VATS.11 Confirmation of the diagnosis is pathological, which is challenging. Glands may be so small that they may not be identified.12 In these cases, immunohistochemistry markers like oestrogen receptor, progesterone receptor and CD10 may be useful.13 Treatment options include medical or hormonal, surgical and combined.1 2 14 Hormonal therapy consists of gonadotropin-releasing hormone (GnRH) analogues, oral contraceptives, aromatase inhibitors, progestogens and androgens. Recently, dienogest or continuous oral contraceptives have been suggested for long-term use as alternatives.15 GnRH antagonists like elagolix are effective by suppressing ovarian hormones.16 Surgical options are pulmonary parenchymal resection, pleural resection and lobectomy.14 These are usually opted when medical therapy fails. Combined therapies have a lower recurrence rate.15 As part of primary emergency management, chest tube placement is done. The index patient had a recurrence of pleural effusion when dienogest was stopped. Since she is nulliparous and wants to conceive a child, treatment is challenging. The hormonal therapy needs to be stopped at some point for her to get ovulation. But this carries the risk of recurrence of pleural effusion. Differentials to be considered in such cases include trauma, coagulopathy, malignancy, pleuritis (like SLE, etc), pulmonary embolism with lung infarct and TE (in young women). Work up to differentiate among these would include eliciting a history of trauma, coagulation parameters, contrast-enhanced CT of the chest, VATS and thoracoscopic biopsy. Immunohistochemistry must be considered in centres wherever available. Patient’s perspective. I am married for 7 years and was trying to have a child. But I started having a cough and difficulty breathing. Initially, doctors told me I have fluid in the chest, and it could be because of tuberculosis. I was started on medicines for the same, but my fluid did not subside. I was referred to the second hospital. After undergoing some more tests and taking a biopsy from my chest, I was told my uterus tissue is deposited in the chest. I came to know; I have a very rare condition. I was started on hormonal treatment, and my fluid subsided. After 6 months, my hormones were stopped as I wanted to try to have a child. Unfortunately for me, I developed breathing difficulty again after 2 weeks, and I consulted the hospital. Again I was told to have fluid in the chest, which was drained. I was restarted on hormones which I am continuing for the last 6 months. I am anxious about what will happen next time hormones are stopped, and will I ever have a child? Learning points. Thoracic endometriosis requires a high degree of suspicion to be diagnosed, especially in geographical areas where other causes of effusion like infections and malignancy are predominant. Diagnosis is challenging and requires biopsy with video-assisted thoracoscopy. Management includes long-term therapy with hormones. Treatment is challenging in a woman planning to conceive, as stopping the hormone can lead to recurrences. Acknowledgments We acknowledge all the doctors, nurses and supporting hospital staff involved directly/indirectly in the care of the index patient. We acknowledge the patient and family members for giving consent for publishing the case report and for providing patient’s perspective. Footnotes Twitter: @nandanbaikunje Contributors: SC participated in writing the manuscript. NB and GBH participated in patient care, literature review and reviewing the manuscript. SB participated in pathological diagnosis and reviewing the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer reviewed.

- 1.Rawala MS, Khaliq MF, Iqbal MA, et al. A rare case of cyclical hemothorax: thoracic endometriosis syndrome. Case Rep Pulmonol 2018;2018:1–4. 10.1155/2018/9830797 [DOI] [PMC free article] [PubMed] [Google Scholar] - 2.Nair SS. Thoracic Endometriosis Syndrome: A Veritable Pandora’s Box. J Clin Diagn Res 2016. 10.7860/JCDR/2016/17668.7700 [DOI] [PMC free article] [PubMed] [Google Scholar] - 3.Joseph J, Sahn SA. Thoracic endometriosis syndrome: new observations from an analysis of 110 cases. Am J Med 1996;100:164–70. 10.1016/S0002-9343(97)89454-5 [DOI] [PubMed] [Google Scholar] - 4.Channabasavaiah AD, Joseph JV. Thoracic endometriosis: revisiting the association between clinical presentation and thoracic pathology based on thoracoscopic findings in 110 patients. Medicine 2010;89:183–8. 10.1097/MD.0b013e3181df67d5 [DOI] [PubMed] [Google Scholar] - 5.Korom S, Canyurt H, Missbach A, et al. Catamenial pneumothorax revisited: clinical approach and systematic review of the literature. J Thorac Cardiovasc Surg 2004;128:502–8. 10.1016/j.jtcvs.2004.04.039 [DOI] [PubMed] [Google Scholar] - 6.Alifano M, Jablonski C, Kadiri H, et al. Catamenial and noncatamenial, endometriosis-related or nonendometriosis-related pneumothorax referred for surgery. Am J Respir Crit Care Med 2007;176:1048–53. 10.1164/rccm.200704-587OC [DOI] [PubMed] [Google Scholar] - 7.Nezhat C, Lindheim SR, Backhus L, et al. Thoracic endometriosis syndrome: a review of diagnosis and management. JSLS 2019;23:e2019.00029. 10.4293/JSLS.2019.00029 [DOI] [PMC free article] [PubMed] [Google Scholar] - 8.Hirata T, Koga K, Osuga Y. Extra-pelvic endometriosis: a review. Reprod Med Biol 2020;19:323–33. 10.1002/rmb2.12340 [DOI] [PMC free article] [PubMed] [Google Scholar] - 9.Sharma N, Todhe P, Ochieng P, et al. Refractory thoracic endometriosis. BMJ Case Rep 2020;13:e235965. 10.1136/bcr-2020-235965 [DOI] [PMC free article] [PubMed] [Google Scholar] - 10.Parasar P, Ozcan P, Terry KL. Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep 2017;6:34–41. 10.1007/s13669-017-0187-1 [DOI] [PMC free article] [PubMed] [Google Scholar] - 11.Marshall MB, Ahmed Z, Kucharczuk JC, et al. Catamenial pneumothorax: optimal hormonal and surgical management. Eur J Cardiothorac Surg 2005;27:662–6. 10.1016/j.ejcts.2004.12.047 [DOI] [PubMed] [Google Scholar] - 12.Haga T, Kataoka H, Ebana H, et al. Thoracic endometriosis-related pneumothorax distinguished from primary spontaneous pneumothorax in females. Lung 2014;192:583–7. 10.1007/s00408-014-9598-1 [DOI] [PubMed] [Google Scholar] - 13.Kawaguchi Y, Hanaoka J, Ohshio Y, et al. Diagnosis of thoracic endometriosis with immunohistochemistry. J Thorac Dis 2018;10:3468–72. 10.21037/jtd.2018.05.121 [DOI] [PMC free article] [PubMed] [Google Scholar] - 14.Andres MP, Arcoverde FVL, Souza CCC, et al. Extrapelvic endometriosis: a systematic review. J Minim Invasive Gynecol 2020;27:373–89. 10.1016/j.jmig.2019.10.004 [DOI] [PubMed] [Google Scholar] - 15.Fukuda S, Hirata T, Neriishi K, et al. Thoracic endometriosis syndrome: comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis. Eur J Obstet Gynecol Reprod Biol 2018;225:118–23. 10.1016/j.ejogrb.2018.04.021 [DOI] [PubMed] [Google Scholar] - 16.Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 2017;377:28–40. 10.1056/NEJMoa1700089 [DOI] [PubMed] [Google Scholar]