{"paper_id":"8478bf8a-eeac-4feb-82e4-1945e5b1d0f1","body_text":"International Journal of\nRespiratory and Pulmonary Medicine\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\nVolume 5 | Issue 2\nDOI: 10.23937/2378-3516/1410082\n• Page 1 of 5 •\nISSN: 2378-3516\nOpen Access\nCitation: Bataduwaarachchi VR, Jayawardhana J, Weerasinghe C, Sadikeen A, Constantine R, et al. \n(2018) An Asymptomatic Haemorrhagic Pleural Effusion Mimicking Extra-Pulmonary Tuberculosis in \na Young Woman with Thoracic Endometriosis Syndrome: A Case Report. Int J Respir Pulm Med 5:082. \ndoi.org/10.23937/2378-3516/1410082\nAccepted: July 12, 2018; Published: July 14, 2018\nCopyright: © 2018 Bataduwaarachchi VR, et al. This is an open-access article distributed under the \nterms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and \nreproduction in any medium, provided the original author and source are credited\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\nAn Asymptomatic Haemorrhagic Pleural Effusion Mimicking \nExtra-Pulmonary Tuberculosis in a Young Woman with Thoracic \nEndometriosis Syndrome: A Case Report\nVipula R Bataduwaarachchi 1,2*, Jayani Jayawardhana 2, Champa Weerasinghe 2, Aflah Sadikeen2, \nRoshana Constantine3 and Kirthi Gunasekara2\n1Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka\n2Respiratory Medicine Unit, National Hospital of Sri Lanka, Sri Lanka\n3Department of Pathology, National Hospital of Sri Lanka, Sri Lanka\n*Corresponding author: Vipula R Bataduwaarachchi, Department of Pharmacology, Faculty of Medicine, University of Colom-\nbo, PO Box 271, Kinsey Road, Colombo 8, Sri Lanka, Tel: 0094-112697483, Fax: 0094-112697483, E-mail: vipbat7@yahoo.com\nAbstract\nBackground: This case discusses the importance of thor-\noughly investigating a haemorrhagic effusion in a setting \nwhere the tuberculosis is endemic.\nCase report: A young woman presented with an asymp-\ntomatic recurrent right sided pleural effusion. Pleural fluid full \nreport showed neutrophilic and haemorrhagic effusion. Ade-\nnosine deaminase level in the pleural fluid was elevated and \nthe Mantoux test was positive. Microbiological diagnosis was \nnegative, and she was started on anti-tuberculous therapy on \nclinical grounds for extrapulmonary tuberculosis. Diagnostic \nThoracoscopy revealed characteristic appearance suggestive \nof thoracic endometriosis which was confirmed by histology.\nConclusions: Thoracoscopy is valuable in rapid diagnosis \nof pleural based diseases such as thoracic endometriosis. \nIt also provides option to drain tuberculous and other com-\nplicated effusions completely minimising the chance of later \ncomplications. This case discusses the importance of thor-\noughly investigating a haemorrhagic effusion in a setting \nwhere the tuberculosis is endemic.\nKeywords\nHaemorrhagic effusion, Catamenial haemothorax, Tubercu-\nlosis, Thoracic endometriosis syndrome\nList of Abbreviations\nTB: Tuberculosis; TES: Thoracic Endometriosis Syndrome; \nBMI: Body Mass Index; CECT: Contract Enhanced Com-\nputed Tomography; ESR: Erythrocyte Sedimentation Rate; \nCRP: C-Reactive Protein; LDH: Lactase Dehydrogenase;\nANA: Antinuclear Antibody; RF: Rheumatoid Factor; HIV: \nHuman Immune Deficiency Virus; USS: Ultra-Sound Scan; \nRBC: Red Blood Cells; AFB: Acid- Fast Bacilli; ADA: Ade-\nnosine Deaminase; GeneXpert MTB/RIF: Mycobacterium \nTuberculosis and Resistance to Rifampicin; BCG: Bacillus \nCalmette-Guérin; ATT: Anti-tuberculous Therapy; VATS: Vid-\neo Assisted Thoracoscopic Surgery; SLE: Systemic Lupus \nErythematosus; GnRH: Gonadotropin-Releasing Hormone\nBackground\nHaemorrhagic pleural effusion is defined as pleural \nfluid hematocrit greater than 50% of the patient’s blood \nhematocrit. Spontaneous haemorrhagic effusions have \na broad differential diagnosis which includes TB, malig -\nnancy, connective tissue disorders, pancreatic fistulas, \nleaking aortic aneurysms and other vascular malforma-\ntions, TES, ovarian hyperstimulation syndrome etc [1-4]. \nCo-existing aetiologies can lead to diagnostic and man-\nagement dilemma among physicians. TB remains one of \nthe most frequent causes of pleural effusions globally, \nhence always is high up in the list of differential diag -\nnoses [5].\nEndometriosis is characterised by the presence of \nhormone sensitive endometrial tissue outside the uter-\nine cavity. It is more commonly encountered in the de-\npendent parts of the pelvis such as ovaries, fallopian \ntubes, uterine ligaments, pelvic peritoneum, cervix, la-\nCASe RepoRt\nCheck for\nupdates\n\nISSN: 2378-3516\nDOI: 10.23937/2378-3516/1410082\n• Page 2 of 5 •\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\nThe CECT scan of the thorax showed moderate to se-\nvere right sided pleural effusion extending into the right \nmajor fissure with associated basal collapse of the right \nlower lobe and mild volume loss with elevated right \nhemidiaphragm. Fibrotic parenchymal bands were seen \nin the right middle lobe with fibrous septa attached to \nthe diaphragm. There were no intra-parenchymal le-\nsions present (Figure 2).\nInflammatory markers were not elevated with the \nESR of 07 mm and the CRP level below 3.0 mg/dL. Clot -\nting profile and liver function tests were within normal \nranges. Serum LDH level was 437 U/L (140 - 280 U/L). \nAutoimmune marker panel including ANA and RF was \nnegative. HIV, hepatitis and syphilis serological screen -\nings were also negative. The USS of abdomen was nor-\nmal and there was no clinical or radiographic evidence \nof pelvic endometriosis.\nbia, and the vagina [6]. TES is a distinct category with the \npresence of functional endometrial tissue in or around \nthe lung. TES has four main clinical subtypes: catamenial \npneumothorax, catamenial haemorrhagic effusion, hae-\nmoptysis and pulmonary nodules.\nThis case discusses the importance of thoroughly in-\nvestigating a haemorrhagic effusion in a setting where \nthe prevalence of TB is high and the dilemma in diagno-\nsis and management in the presence of TES.\nCare Report\nA 43-year-old unmarried Sri Lankan woman working \nin Maldives was referred to the Respiratory Medicine \nunit of the National Hospital of Sri Lanka. She was di -\nagnosed with a right sided pleural effusion in the chest \nX-ray performed during her annual medical screening. \nshe had been asymptomatic preceding this incident and \nthereafter. An abnormality was detected in her chest \nX-ray one year prior to this incident but she had not \nbeen further evaluated. Her previous chest X-ray was \nnot available but according to her, it was also a right \nsided abnormality. She had never smoked, and her fam-\nily history was not significant for any specific medical \nillness. There were no clinical clues to suspect an immu-\nnocompromised status.\nOn examination, she was apparently healthy with a \nBMI of 22 Kg/m\n2. Respiratory examination was compati-\nble with a moderate right sided pleural effusion. Repeat \nchest X-ray confirmed the persistence of an encysted ef-\nfusion (Figure 1). Based on the clinical picture it was de-\ncided to continue with ATT on empirical basis which had \nalready been started in Maldives. She was on isoniazid \n(10 mg/kg), rifampicin (15 mg/kg), pyrazinamide (35 mg/\nkg) and ethambutol (20 mg/kg) and we converted it to \nmultidrug combination tablets. Further diagnostic inves-\ntigations were planned to explore the definite diagnosis.\n         \nFigure 1: Postero-anteror (a) and lateral (b) chest X-rays of the patient shows the pleural effusion.  Lateral chest X-ray \nshowed ‘rock of Gibraltar sign’(arrow) which is characteristic of subpulmonic effusions. \n         \nFigure 2: Contrast CT of the thorax (single section is \nshown) shows a right sided pleural effusion.\n\nISSN: 2378-3516\nDOI: 10.23937/2378-3516/1410082\n• Page 3 of 5 •\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\nand microbiological analysis. Cytology revealed reac -\ntive mesothelial cells. Histology confirmed endometrial \ntissue with abundant well-formed glandular structures \nconfirming the diagnosis of TES (Figure 4). Microbio -\nlogical testing was negative for TB in the Thoracoscopy \nsamples.\nThe patient was referred to a Gynaecologist for fur-\nther treatment for TES and ATT was continued as a case \nof latent TB after discussing at the multidisciplinary \nmeeting. Currently, she is on hormonal treatment with \nmonthly intra-muscular medroxy progesterone acetate \n150 mg injections and so far, six doses have been given. \nHer most recent chest X-ray shows no progression of the \neffusion. The ATT course is finished with two months of \nintensive phase (with 4 drugs) and four months of con -\ntinuation phase (with 2 drugs). She will be followed up \nThe pleural fluid analysis was exudative in type with \nabundant RBCs and predominant neutrophils (Table 1). \nIt also showed undefined cells in significant amounts. \nThe direct smears of pleural fluid were negative for AFB. \nADA level in the pleural fluid was marginally elevated. \nHowever, the GeneXpert MTB/RIF test of the pleural \nfluid was negative.\nSputum examination was negative for AFB. Her \nMantoux reading was 14 mm which is significant in the \ncontext of previous BCG vaccination. She underwent \nfibro-optic bronchoscopy which did not reveal any en-\ndobronchial lesions followed by diagnostic thoracosco -\npy. Haemorrhagic fluid was noted in the right pleural \ncavity. There was abundant adhesion formation at the \nright costo-diaphragmatic angle suggestive of a chron -\nic inflammatory process. Characteristic blueberry spots \nwere noticed on the diaphragmatic pleura (Figure 3).\nWe suspected TES at this point but were not confi -\ndent enough to exclude tuberculosis. Brush, wash and \nbiopsy samples were sent for cytological, histological \n         \nFigure 3: Thoracoscopic view of the diaphragmatic and parietal pleura. Islands of vascular areas interspersed with haemor-\nrhagic spots (a) on the parietal surface of the pleura along with multiple soft cyst-like nodules (b) on the diaphragmatic and \nvisceral pleural surfaces.\n         \nFigure 4: Histology of the pleural biopsy shows well-formed \nendometrial type glands lined by a columnar epithelium bear-\ning regular nuclei, surrounded by endometrial type stroma. \nThe glands and stroma show bland nuclear features. Findings \nare compatible with endometriosis of the pleura.\nTable 1: Pleural fluid analysis results from pleural aspiration. \nParameter Result \nAppearance Blood stained\npH 8.0\nGlucose 99.3 mg/dL\nProtein 48.1 g/L\nLDH 954.4 U/L\nCholesterol 129.4 mg/dL\nPleural fluid haematocrit \nBlood haematocrit \n25.5\n40.1\nADA 56 U/L\nLeucocytes 568 per cu mm\nPolymorphs 50%\nLymphocytes 20%\nUndefined cells 30%\n\nISSN: 2378-3516\nDOI: 10.23937/2378-3516/1410082\n• Page 4 of 5 •\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\nco-exist with other pulmonary pathologies. Therefore, \ninvasive investigations are justified early in the course \nof management.\nDiagnostic thoracoscopy and sampling is the best \napproach in an undiagnosed effusion with controversial \nfindings. This case highlights the importance of Thora -\ncoscopy for the rapid diagnosis of TES presenting as an \neffusion due to its characteristic macroscopic appear-\nances such as red lesions, and endometriotic spots [16]. \nEarly Thoracoscopy has an additional advantage of pro-\nviding the option for draining pleural fluid completely \nwithout leaving any radiological stigmata such as pleu -\nral thickenings. It will also provide the option to perform \nsurgical interventions such as curettage or pleurodesis \nfor endometriosis following a timely histology report. \nHowever, this is debatable as it has not been properly \nassessed in controlled clinical trials but is an area which \nneeds further investigations.\nReasons for the silent nature of the TES in this case \nwere not very clear which usually presents with month-\nly cyclical symptoms in conjunction with menstruation \n[19]. Probably minor bleeding may have concealed with-\nin a fibrotic pocket under the subpulmonic area with -\nout irritating the pain sensitive parietal pleura. Release \nof chemical substances from the endometrial glands \nthemselves to suppress pain is a theoretical possibility. \nInfrequent thoracic endometriosis without monthly re -\ncrudescence could be a reason for silent presentations. \nChronic cyclical inflammation leads to serious compli -\ncations if left unattended such as trapped lung due to \npleural thickenings. Permanent stigmata on the chest \nX-ray can also cause problems in circumstances such as \nvisa and job applications.\nManagement of TES include medical and surgical \ntreatment modalities. Suppression of the ectopic en-\ndometrium by inhibiting ovarian oestrogen secretion \nby hormonal treatment such as oral contraceptive pills, \nprogestins, danazol or GnRH analogues has been widely \nused [9,20]. It is recommended to try hormonal therapy \nas the first choice in mild to moderate disease. However, \nif the response is poor surgical intervention is required. \nPneumothorax and haemothorax recur in greater than \n50% of the patients despite hormonal treatment, sug-\ngesting that regression of the pathological process is \nnot complete and or that recurrent embolisation from \npelvic foci [21]. Surgical ablation, pleurodesis or pleu -\nrectomy can be tried if the medical treatment is failed. \nOccasionally, patients can be refractory to all of the \nabove treatment modalities. These patients respond \nto hysterectomy with bilateral salpingoophorectomy \n[22]. However, hormonal therapy should be continued \nto prevent recurrences following surgical treatment \n[23,24]. More evidence-based guidelines are required \nin future regarding the diagnosis and treatment of TES \nand multidisciplinary decision making will greatly help \nwhen managing complicated patients.\nby the Gynaecologist monthly and by the respiratory \nteam six monthly. If there is any symptomatic or radio -\nlogical progression plan is to evaluate further with a \nCECT scan of the thorax to decide on VATS and ablation \nor pleurodesis.\nDiscussion\nEndometriosis can affect up to 15% of women in their \nreproductive years [7,8]. The mean age at presentation \nof TES is 35 years. Peak incidence for TES is reported \nbetween 30 and 34 years. Pneumothorax was the most \ncommon presentation (73%), followed by hemothorax \n(14%), hemoptysis (7%), and lung nodules in (6%) in a \nlarge case series of 110 patients. The right hemithorax \nwas involved in more than 90% of all manifestations \nwhich is compatible with our patients’ presentation. \nHemothorax was more often associated with the pres-\nence of pleural and pelvic endometriosis compared with \nother manifestations (P < 0.003, P < 0.02) [9]. Although \npelvic endometriosis was not present in our patient \nshe need to be followed up for future occurrence. In a \nsetting where pulmonary tuberculosis is endemic, TES \ncauses diagnostic confusion in the absence of positive \nmicrobiological evidenced for TB. Therefore, timely clin-\nical judgement and selecting the correct line of investi-\ngations are mandatory.\nOur patient had a neutrophil predominant effusion. \nAlthough, lymphocyte predominant pleural effusions \nare more common with pleural TB, neutrophil predom-\ninance does occur in tuberculous effusions [10]. Mar-\nginally high ADA levels in the pleural fluid can cause \ndiagnostic difficulties in the absence of microbiological \nconfirmation for TB. ADA levels can be elevated in any \nchronic inflammatory process [11]. ADA levels > 50 IU/L \nsupport the diagnosis of TB in high prevalence areas, \nbut do not exclude or differentiate tuberculosis from \nother diagnoses. Pleural fluid ADA has a high sensitivity \n(99%) but a lower diagnostic accuracy (75%) especial-\nly in the presence of chronic inflammatory disorders of \nthe pleura [12,13]. On the other hand, the presence of \nreactive mesothelial cells in the pleural fluid in our case \nis against the diagnosis of pleural tuberculosis [14]. Her \nMantoux reading was 14 mm and it was just below the \ncutoff for a patient with previous BCG vaccination (cut \noff - 15 mm). Mantoux test is a sensitive but non-spe -\ncific test in the diagnosis of active tuberculosis [15]. \nEffusions in the subpulmonic space are less evident in \nclinical examination and in chest radiography. CECT tho-\nrax is a very useful investigation in this context. Thoracic \nimaging seems less useful as a definitive diagnostic tool \nin the diagnosis of TES as it does not have a characteris-\ntic radiological pattern [16]. In an endemic area where \nlatent tuberculosis is common, it is mandatory to ex-\nclude active tuberculosis by other investigations in the \npresence of a significantly positive Mantoux reading. \nEmpirical ATT is an acceptable practice in this context \nfor patients in endemic areas [17, 18]. Tuberculosis can \n\nISSN: 2378-3516\nDOI: 10.23937/2378-3516/1410082\n• Page 5 of 5 •\nBataduwaarachchi et al. Int J Respir Pulm Med 2018, 5:082\n5. Vorster MJ, Allwood BW, Diacon AH, Koegelenberg CF \n(2015) Tuberculous pleural effusions: advances and con-\ntroversies. J Thorac Dis 7: 981-991.\n6. Taylor RN, Lebovic DI (2009) Endometriosis. In: Strauss \nJF, Barbieri R, Yen and Jaffe’s reproductive endocrinology: \nphysiology and clinical management. (6\nth edn), New York: \nElsevier, 577-595. \n7. Alifano M, Trisolini R, Cancellieri A, Regnard JF (2006) \nThoracic endometriosis: current knowledge. Ann Thorac \nSurg 81: 761-769.\n8. Vinatier D, Orazi G, Cosson M, Dufour P (2001) Theories of \nendometriosis. Eur J Obstet Gynecol Reprod Biol 96: 21-34.\n9. Joseph J, Sahn SA (1996) Thoracic endometriosis syn-\ndrome: new observations from an analysis of 110 cases. \nAm J Med 100: 164-170.\n10. Choi H, Chon HR, Kim K, Kim S, Oh K-J, et al. (2016) Clin-\nical and Laboratory Differences between Lymphocyte- and \nNeutrophil-Predominant Pleural Tuberculosis. PLoS One \n11: e0165428. \n11. Piras MA, Gakis C, Budroni M, Andreoni G (1978) Adenos-\nine deaminase activity in pleural effusions: an aid to differ-\nential diagnosis. Br Med J 2: 1751-1752.\n12. Karkhanis VS, Joshi JM (2012) Pleural effusion: diagnosis, \ntreatment, and management. Open Access Emerg Med 4: \n31-52.\n13. Ramadan SM, Laz NI, Eissa SAL, Elbatanouny MM, Mo-\nhammed MF (2017) Diagnostic dilemma in tuberculous \npleural effusion. Egypt J Chest Dis Tuberc 66: 327-330. \n14. Hurwitz S, Leiman G, Shapiro C (1980) Mesothelial cells in \npleural fluid: TB or not TB? S Afr Med J 57: 937-939.\n15. Loh K (2011) Role of mantoux test in the diagnosis of tuber-\nculosis. Malays Fam Physician 6: 85-86.\n16. Hwang SM, Lee CW, Lee BS, Park JH (2015) Clinical fea-\ntures of thoracic endometriosis: A single center analysis. \nObstet Gynecol Sci 58: 223-231. \n17. National Manual for Tuberculosis Control [Internet] (2016) \nNational Programme for Tuberculosis Control and Chest \nDiseases.  \n18. Loh LC, Abdul Samah SZ, Zainudin A, Wong GLS, Gan \nWH, et al. (2005) Pulmonary disease empirically treated as \ntuberculosis-a retrospective study of 107 cases. Med J Ma-\nlaysia 60: 62-70. \n19. Nair SS, Nayar J (2016) Thoracic Endometriosis Syndrome: \nA Veritable Pandora’s Box. J Clin Diagn Res 10: 04-08.\n20. Marshall MB, Ahmed Z, Kucharczuk JC, Kaiser LR, Shrager \nJB (2005) Catamenial pneumothorax: optimal hormonal and \nsurgical management. Eur J Cardiothorac Surg 27: 662-666. \n21. Alifano M, Roth T, Broët SC, Schussler O, Magdeleinat \nP, et al. (2003) Catamenial pneumothorax: a prospective \nstudy. Chest 124: 1004-1008.\n22. Rivas de Andrés JJ, Jiménez López MF, Molins López-\nRodó L, Pérez Trullén A, Torres Lanzas J, et al. (2008)  \n[Guidelines for the diagnosis and treatment of spontaneous \npneumothorax]. Arch Bronconeumol 44: 437-448.\n23. Joseph Vempilly J (2017) Clinical features, diagnostic ap-\nproach, and treatment of adults with thoracic endometriosis \n- [Internet]. \n24. Moffatt SD, Mitchell JD (2002) Massive pleural endometrio-\nsis. Eur J Cardiothorac Surg 22: 321-323.\nConclusions\nTES should always be suspected in a woman of re -\nproductive age group presenting with prolong or recur-\nrent haemorrhagic effusion especially on the right side. \nTB is an important diagnostic consideration in any pleu-\nral effusion in endemic areas which can cause diagnostic \nand treatment dilemma in the absence of microbiolog -\nical confirmation in the presence of other overlapping \npulmonary pathologies. Early thoracoscopy is a useful \ndiagnostic and treatment option in pleural TB as well as \nTES.\nEthics Approval and Consent to Participate\nWritten consent was obtained from the patient use \nclinical data and images for research purposes.\nConsent for Publication\nWritten consent was obtained from the patient for \npublication.\nCompeting Interests\nThe authors declare that they have no competing in-\nterests.\nAcknowledgements\nThe authors acknowledge the staff at the Depart-\nment of Pathology, National Hospital of Sri Lanka for \ntheir help for histological analysis and the staff of the \nRadiology Department of the National Hospital of Sri \nLanka for help in radiological studies.\nAuthors Contributions\nVRB conceived the report and wrote the manuscript; \nCW coordinated patient management and presented \nthe case in the multidisciplinary meeting; JJ helped in \nthe management and follow up of the patient; AS per-\nformed bronchoscopy and Thoracoscopy in the patient; \nRC analysed the histological material and critically read \nthe manuscript; KG took management decisions. All the \nauthors have read and approved the final manuscript.\nFunding\nNot applicable.\nReferences\n1. Patrini D, Panagiotopoulos N, Pararajasingham J, Gvinian-\nidze L, Iqbal Y, et al. (2015) Etiology and management of \nspontaneous haemothorax. J Thorac Dis 7: 520-526.\n2. Dixit R, Sharma S, Dave L (2008) Massive haemothorax in \nasymptomatic pseudocyst pancreas. Lung India 25: 126-\n128.\n3. Tristano AG, Tairouz Y (2005) Painless right hemorrhagic \npleural effusions as presentation sign of aortic dissecting \naneurysm. Am J Med 118: 794-795. \n4. Alaraj A (2013) Symptomatic hemorrhagic pleural effusion: \nA rare presentation of ovarian hyperstimulation syndrome: \nA Case Report. Int J Health Sci 7: 347-350.","source_license":"CC0","license_restricted":false}