Medical management of bronchial endometriosis: Case report and literature review

We are presenting 29 year old female complaining of catamina l haemoptysis 3 months post -delivery of her second child. She had no previous history of endometriosis or chronic pelvic pain. She was investigated thoroughly by re spiratory and immunology teams for all possible diagnosis and clinically the final diagnosis was bronchial endometriosis. This case showed that combined oral contraceptive pills has successful role of management of lung endometriosis.

bronchial endometriosis, post-delivery, respiratory, immunology

Endometriosis is the presence of functional endometrial-like tissue outside of the uterus It is most commonly in the ovaries, uterosacral ligaments, and pelvic peritone um the condition was first reported in 1860 [1]. Endometr iosis is reported in 5% to 15% of females worldwide during t heir reproductive life [2]. In some rare cases ectopic endometrial tissue has been found in distant sites, such as the umbilicus, abdominal scars, breasts, the extremities, pleural cavity and lung parenchyma [3, 4] . The symptoms of extra -pelvic endometriosis are not always synchronous with the menstrual cycle, and diagnosis can be particularly difficult. Bronchial endometriosis is an uncommon condition, a nd usually associated with cyclical haemoptysis and chest pain. Diagnosis mainly depends on clinical suspicion base d on presenting symptoms and history, with confirmation by histopathological assessment [5]. Clinical examination often reveals only occult signs and symptoms. Reported cases that had cyclical pain and haemoptysis often have severe decidual adhesions and distortion of tissue around the decidua [6]. Additionally, the pathologist’s role is made difficult by the atypical histopathological feature s, from typical endometrial glands to an abundance of fibrous tissue, on a background of lunch parenchyma and bronchial tissue. The major modality of treatment for bronchial endometriosis is surgical excision through bronchos copy, which usually provides a positive outcome [7]. Medical management such as use of contraceptive progestogen s, gonadotropin-releasing hormone agonists, androgens, and non-steroidal anti-inflammatory drugs have been used with mixed effect, and often only have benefits for limi ted time periods, and the long term side effects of chronic use [8]. Case Report A 27 year old female, Para 2+0 presented to a terti ary university hospital complaining of several episodes of cyclical cataminal haemoptysis (coughing blood duri ng menstruation). The patient had a prior uncomplicate d spontaneous normal vaginal delivery of her second child 3 months previously, with a routine postnatal course. Her menses resumed eight weeks post -delivery. Despite having no pre-existing respiratory problems, she developed severe new onset pulmonary bleeding post-partum, coinciding with menstruation. Each episode of haemoptysis was estimated at 15ml volume with each period, and she presented to acutely to the hospital emergency department and required i npatient admission each time. The patient never reported any cyclical pelvic pain, or abnormal gynaecological symptoms. She was initially assessed by the respiratory physicians, a s each episode accompanied with significant dyspnoea. On physical examination, right -sided coarse crepitations with decreased air entry was noted on auscultation. PA Chest radiography demonstrated an opacity and regular mar kings in the right lower lung lobe. All haematological an d biochemical investigations, including full blood co unt, c - reactive protein, liver function tests and renal fu nction tests, were normal. To further assess, a CT pulmonary angi ogram (CTPA) was arranged. This identified a focal area o f “ground glass” changes within the superior segment of the right lower lobe, and was deemed to likely be eithe r infectious or inflammatory by the reporting radiologist. No pulmonary embolus, plural effusion, thoracic lymphadenopathy or osseous abnormality were seen. S he was started on broad spectrum antibiotics (pending microbiological analysis of sputum culture) with th e recommendation to r epeat the CT thorax in 4 -6 weeks, and discharged home for outpatient follow up with the report. A month after the initial presentation she re -attended the emergency room with heavy respiratory bleeding and shortness of breath, again with menstruation. A re peat CTPA was performed, and interestingly this showed a n increase in the previously identified “ground -glass” changes with new extension into the anterior aspect of the apical segment of the right lower lobe. No evidence of pul monary haemorrhage or nodule s were seen. During this repeat CTPA the patient had active haemoptysis. Following review and discussion at the regional respiratory multi -disciplinary meeting a bronchoscopy was recommend, and subsequen tly completed during this emergency admission. Bronchoalviolar lavage (BAL) (it is a diagnostic method of the lower respiratory system in which a bronchoscop e is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amount of fluid intro duced and then collected for examination) was performed, and histology revealed an abundant alveolar presence. International Journal of Reproduction, Gynaecology and Obstetrics www.gynecologyjournal.in 11 Eosinophils were not identified on May Grünewald-Giemsa (MGG) Stain (MGG is stain used for staining of blood, bone marrow smears and clinical cytological specimens), and no malignant cells were seen. A full immunology screen was then completed including: Anti -neutrophil cytoplasm antibodies (ANCA) and DNA by crithidia luciliae (it is a flagellate parasite that uses the housefly, Musca domestica, as a host) [20]. As part of the fa mily of Trypanosomatidae, it is characterised by the presence of a kinetoplast, a complex network of interlocking circular double-stranded DNA (ds DNA) molecules, which were negative. Complement C3 and C4 levels were within normal range. The respiratory team at this stage noted that the haemoptysis was cataminal – as it occurred recurrently during the days when the patient was actively menstruating. A gynae cology consultation was then sought. She had no previous gynaecological history of note. A recommendation to commence the patient on a course of triptorelin pam oate (Decapeptyl) 11.25mg injection for 3 months to achi eve ovarian and menstrual suppression was made by the attending consultant. Due to the possibility of hypoestrogenic vasomotor symptoms, and po tential osteopenia if longer term use was needed, the abili ty to incorporate add -back hormone replacement therapy (HRT) for symptom control and bone-protection was discussed. An ultrasound pelvis was performed to assess for struc tural abnormalities, but wa s unremarkable. A provisional working diagnosis of pulmonary endometriosis was no w made, and an MRI Thorax was arranged to further investigate. Unusually this showed no T1 hyper -intensities within the lung parenchyma or plural or diaphragm t o suggest endometriosis deposits (figure 3, 4). No episodes of cataminal haemoptysis occurred in th e 3 months followed the triptorelin pamoate injection. A subsequent CT thorax showed complete resolution of “ground-glass” opacification, with appearance suspicious for prior pulmonary haemorrhage in the anterior basal low er lobe, but with no acute findings suspicious for cur rent pulmonary haemorrhage (figure 1, 2). She had minimal hormonal side effects from the ovarian suppression, with only mild but tolerable episodes of warm flushing and minor mood change. For long term management a patient centred discussi on was had outlining risks and benefits of the treatment o ptions. With no personal contraindications for combined ora l contraceptive pill use, the patient was commenced on Yasmin (0.03mg Ethinylestradiol/3mg Drospirenone) f or three months continuously, avoiding the pill-free weeks. She again suffered no episodes of cataminal haemoptysis throughout, however did reported ongoing light head aches. She was switched Microlite (100mcg Levonorgestrel/20mcg Ethinylestradiol) for 6 months, again “back -to-back”, with no break. She reported no adverse side effects for three months, but at this point had a small break -through bleed, together with some mild chest pain, but no haemopty sis. Since then for the last she has been maintained on the Levonorgestrel/Ethinylestradiol combination, taking pill free period every six months for one week, without complaints or further episodes. Fig 1 Fig 2 Fig 3 Fig 4 International Journal of Reproduction, Gynaecology and Obstetrics www.gynecologyjournal.in 12

Bronchial endometriosis is a rare condition of non -pelvic endometriosis [9] . Approximately 60% of cases also have true co-existing pelvic endometriosis [9, 10, 11] . Simultaneous extra-pelvis endometriosis of the diaphragm and the visceral pleura are found in 38.8% and 29.6% of cases respec tively [10]. Endometriosis of the lung parenchyma is much less common [9, 11]. The pathophysiology of cyclical haemoptysis remains unclear, though three existing predominant theories dominate the literature [12]. The leading hypothesis, proposed by Schron and Ruysh [13], is a variant of Sampson’s theory of retrograde menstruation. This m odel suggests that endometrial -like cells enter the peritoneal cavity then pass to pleural space by lymphatic chan nels. An alternative second hypothesis considers that high l evels of prostaglandin F2 at the time of ovulation may resul t in vasospasm and associated ischemia in the lung paren chyma. A combination of prostaglandin -induced bronchospasm, may cause the alveoli to rupture resulting in haemo ptysis, and also explain the associated risk of pneumothora x with thoracic endometriosis [13]. Thirdly, an anatomical theory is that the loss of t he cervical mucus plug during menses

in communication between the environment, peritoneal cavity, and subsequently the pleural spa ce [14]. As many women will have retrograde menstruation with t heir monthly periods, yet thoracic endometriosis is rar e, none of these proposed models can completely explain this phenomenon. More recent theories in molecular and cellular pathophysiology have looked at a spread of endometr ial micro RNAs through exosomal trafficking [15], though this is a novel theory for e xtra-pelvic endometriosis spread and as of yet has not been demonstrated in bronchial endometriosis. Diagnosis of bronchial endometriosis is almost alwa ys grounded initially on clinical suspicion [11]. The majority of patients present to hospital with a combination of cataminal haemoptysis, shortness of breath, cough, and pleuri sy. Investigations including chest radiography, CT thor ax, MRI thorax and bronchoscopy can also give help to suppo rt the clinical suspicion for a diagnosis of bronchial endometriosis. However, in the majority of cases reported, diagnosis is usually made, and treatment performed, with the use of video -assisted thoracoscopic surgery (VATS) [14]. This allows direct visualisation of any pathology, and targeted biopsy of any suspected endo metriotic lesion [14]. The initial management is often symptom control thr ough medical treatment; which brings side -effect profiles, recurrence risks and long -term high cost to the patients without definite treatment of the lesion. Surgical interventions s uch as chemical pleurodesis, pleurectomy, resection and lobectomy have proven successful management options [14]. While in this case no evidence of pelvic endometrio sis or gynaecological disease was found on radiological im ages; the CT findings for pulmona ry endometriosis may include well-defined opacities, nodular lesions, thin-wall cavities, or bullous formations, but in cases with haemoptysis t hey have transient radiologic densities in the part of the l ung [16]. In this case, the CT revealed an opacity a t the anterior part of the lower right lobe, histopathology of bronchial l avage samples did not indicate ectopic endometrial pathol ogy. Generally, diagnostic requirements for bronchial endometriosis is the presentation of periodic haemo ptysis that is synch ronous with menstruation. Most previously reported cases were diagnosed based on the clinical history of the patient; and a histological confirmation of ectopic endometriosis is not always completed and reported. Unfortunately, though bronchoscopic attempt s at tissue sampling were made, we were unable to get positive histological samples. However, the presence of cata minal haemoptysis, synchronous to menses combined with a response to ovulation suppression confirmed the diagnosis. Recently, VATS for surgica l resection to treat cyclical haemoptysis was reported to be safer and less invas ive than lobectomy [17, 18, 19] . Most of the time management of cases of endometriosis treated with hormonal therapy, typ ically gonadotrophic-releasing hormone analogs, or pro stogenic drugs, but these remain controversial. We report he re that a light dose of combined oral contraceptive pill cont inuous use for one year gave excellent symptomatic relief for our patient with this benign thoracic lesion.

We present the use of the combined oral contraceptive pill for symptomatic treatment of bronchial endometriosis, as an effective option for medical management.

Thanks to Dr. Conor Harrity for his contribution as the lead of the gynaecology service in B eaumont Hospital and Dr. Elkharouf and Dr. Amy Worrall for their contributio n to the manuscript.

1. Fleishman SJ, Davidson JF. Vicarious menstruation, a likely case of pulmonary endometriosis. Lancet. 195 9; 2(7093):88-89. 2. Schuld J, Justinger C, Wa gner M, Bo hle RM, Kollmar O, Schilling MK et al. Bronchobiliary fistula: a rare complication of hepatic endometriosis. Fertil Steri l. 2011; 95(2):804-808. 3. Hilaris GE, Payne CK, Osias J, Cannon W, Nezhat CR. Synchronous rectovaginal, urinary bladder, and pulmonary endometriosis. JSLS. 2005; 9(1):78-82. 4. Simoglou C, Zarogoulidis P, Machairiotis N, Por podis K, Simoglou L, Mitrakas A. et al . Abdominal wall endometrioma mimicking an incarcerated hernia: a case report. Int J Gen Med. 2012; 5:569-571. 5. Giudice LC, Kao LC. Endometriosis. Lancet. 2004 ; 364(9447):1789-1799. Doi: 10.1016 /S0140-6736(04) 17403-5. 6. Suginami H, Hamada K, Yano K. A case of endometriosis of the lung treated with danazol. Obs tet Gynecol. 1985; 66(3 Suppl):68S-71S. 7. Park YB, Heo GM, M oon HK, Cho SJ, Shin YC, Eom KS. Et al. Pulmonary endometriosis resected by video - assisted thoracoscopic surgery. Respirology. 2006 ; 11(2):221-223. Doi:10.1111/j.1440-1843.2006.00829.x. 8. Shiota Y, Umemura S, Arikita H, Ho rita N, Hiyama J, Tetsuya Ono T et al. A case of parenchymal pulmonary endometriosis, diagnosed by cytologic examination o f bronchial washing. Respiration. 2001 ; 68 (4):439. Doi: 10.1159/000050545. 9. Schwarz O. Endometriosis of the Lung. Am J Obstet Gynecol. 1938; 36:887-889. 10. Veeraswamy A, Lewis M, Mann A , Koti kela S, Hajhosseini B, Nezhat C et al . Extragenital endometriosis. Clin Obstet Gynecol. 2010; 53 (2):449- International Journal of Reproduction, Gynaecology and Obstetrics www.gynecologyjournal.in 13 466. 11. Rousset-Jablonski C, Alifano M, Plu -Bureau G et al . Cata- menial pneumothorax and endometriosis -related pneumothorax: clinical features an d risk factors. Hum Reprod, 2011. 12. Peikert T, Gillespie DJ, Cassivi SD. Catamenial pneumothorax. Mayo Clin Proc. 2005; 80(5):677-680. 13. Nezhat C. Pelvic pain, Infertility, Pregnancy and Endometriosis: Ancient Conditions, Ancient Correlations and their Ancient Treatments. Fertil Steril accepted for publication, 2012. 14. Cowl CT, Dunn WF, Deschamps C. Visualization of diaphragmatic fenestration associated with catameni al pneumothorax. Ann Thorac Surg . 1999; 68 (4):1413- 1414. 15. Klemmt PA, Starzinski -Powitz A. Molec ular and cellular pathogenesis of endometriosis. Current women's health reviews. 2018; 14(2):106-16. 16. Orriols R, Munoz X, Alvarez A, Sampol G: Chest CT scanning: utility in lung endometriosis. Respir Med . 1998; 92(6):876-877. 17. Park YB, Heo GM, M oon HK, Cho S J, Shin YC, Eom KS. Et al. Pulmonary endometriosis resected by video - assisted thoracoscopic surgery. Respirology. 2006; 11(2):221-223. 18. De Z iegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and managem ent. Lancet. 2010; 376(9742):730-738. 19. Lee CH, Huang YC, Huang SF, Wu YK, Kuo KT. Thoracic endometriosis: rare presentation as a soli tary pulmonary nodule with ecc entric cavitations. Thorax. 2009; 64(10):919-920. 20. Jenkins DW. "Pathogens, Parasites and Predators of Medically Import ant Arthropods. Annotated List and Bibliography". Bull. World Health Organ . 1964; (30suppl):1-150.