Recurrent catamenial hemoptysis: diagnostic challenges and management strategies—a case report

Catamenial hemoptysis (CH) is a rare, known disease for which diagnosis is crucial and treatment is indefinite. In this case report, CH was identified 2 years ago while taking medical history of the patient. It has disclosed hemop- tysis at night with breathlessness that was concurrent with her menses every month for the past 6 months. A series of radiological tests followed by a bronchoscopic examination during menses confirmed the diagnosis. A complex fluid-filled cystic lesion with few air foci in the right lower lobe superior segment with ground glass opacity was seen by a CT scan test. Subsequent bronchoscopy examination showed an active bleeding site at the right lower lobe superior segment. The bronchial wash tests were negative for microbial infections as well as for malignancies. Bron- chial artery embolization (BAE) was done and it ceased the hemoptysis. However, it recurred after 2 years of the BAE procedure. The symptoms and amount of hemoptysis were milder; hence, repeated BAE was not required. Earlier, the patient refused hormonal therapy (HT) owing to its side effects, but this time, she accepted HT. After 2 months of HT, hemoptysis gradually ceased. If complications arise in the future, then surgical treatment along with HT (combi- nation therapy) would be the course of treatment. The diagnosis of CH is challenging, and treatment procedures vary from patient to patient; hence, they are customised. Hormones regulate the CH recurrence even though the symp- toms have ceased after treatment. Therefore, regular follow-up and close vigilance are crucial requirements.

Catamenial hemoptysis, Bronchial artery embolization (BAE), Endometriosis, Menstruation, Case report

Endometriosis of the thorax or lung is a rare disease, and the associated CH disorder is even rarer [1]. Because of CH in patients, it results in bleeding from the lung endo - metrial site during menstruation. Endometrial tissue is the source of bleeding which is implanted either in the lung parenchyma, pleura, or airways and is triggered by the circulating sex hormones [2]. CH is a thoracic endo - metriosis which is either pleural (83%) or pulmonary (17%). CH is reported in around 15% of reproductive-age women, which is further complicated by cases of infer - tility (32%), and chronic pelvic pain (48%). In 1% of cases, endometriosis could also be transformed into malignancy  [3]. Pulmonary endometriosis (PE) could be caused by multifactorial reasons; hence, its patho - physiology is still not clear. Theories suggested are coe - lomic metaplasia, retrograde menstruation, stem cell, and microembolisation theory. Mostly, PE is considered to be caused by peritoneal implants or by invasion of the endometrium into the interstitium of the lung by lym - phatic or hematogenous metastasis during delivery or during pelvic surgeries. All these theories failed to estab - lish a clear mechanism of PE [4]. PE is usually character - ised by CH and it starts and stops with the menstruation cycle of the patient. Symptoms are variable and indefi - nite, too. Because of missing diagnoses and also because *Correspondence: Ashok P . Arbat [email protected] 1 Pulmonary Department, Ketki Research Institute of Medical Sciences, 275, Central Bazar Road, Ramdaspeth, Nagpur, Maharashtra State, India Page 2 of 8Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 of differences of opinion related to the selected line of treatment, optimal management of CH is challenging [5]. Hormonal therapy, conservative treatment, and sur - gical removal of the lesion are the three main treatment plans for CH. Here, we describe a case of CH in a young, unmarried female patient who was treated with bronchial artery embolisation (BAE), but the disease recured after 2  years of treatment. It is to be noted that she had not taken any adjuvant pharmacological treatment during the post-treatment period till the recurrence of the disease, and during this time interval, she was asymptomatic too. Here, in this case report, we are focusing on identifica - tion, diagnosis, and treatment strategies for CH custom - ised in accordance with the patient’s requirements. Case presentation Two years ago, a 19-year-old unmarried female of Asian ethnicity consulted our hospital’s out-patient department (OPD) for complaints of hemoptysis with breathlessness continuously for 8 days with cough and white expectora - tion in the last 7  days. The total amount of hemoptysis was approximately 150–180  ml. A mild cold on and off in the morning was observed. She also complained of abdominal pain for the last 3 days. While taking history, it was revealed that she had suffered from this complex - ity for the past 6 months. Hemoptysis specifically starts at night along with breathlessness and cough, which ceases spontaneously or after taking medications. Cystic airway disease, or cystoid adenoma, was suspected (pro - visional diagnosis) owing to her symptoms. CH was also suspected, as she later mentioned that these conditions occur, especially 2 days before or at the time of menstrua- tion. She denied a history of pelvic endometriosis, uter - ine diseases, bleeding diathesis, or smoking. There was no family history of CH. She was therefore admitted dur - ing menstruation for further treatment and management. At the time of admission, she was afebrile with a temper - ature of 97 °F; blood pressure was 120 mmHg/70 mmHg; pulse rate was 58/min; SPO2 was 98%; respiratory rate was 18/min; and the abdomen was soft. She was con - scious and oriented. The general condition was moderate, and cardiovascular symptoms (CVS) S1 and S2 were nor - mal. She was investigated hematologically, clinically, and radiologically. Her blood investigation result was normal, with haemoglobin (HB) = 13.5, platelets = 341,000, and a negative HIV/HBSAG test result. The chest X-ray showed a thin-walled (with a wall thickness of 2.8 mm) cavitatory lesion of size 3.4 × 3.5 cm seen in the right lower zone, with radiopacity noted in the lower part of the cavity (Fig.  1). A plain and contrast- enhanced multidetector computed tomography (MDCT) chest with pulmonary angiography by a 128-slice MDCT scanner was done (Fig.  2). There was no evidence of a pulmonary embolism. A well-defined cavitary lesion (38 × 32 × 24 mm) was showing air-fluid level with high- density content in the superior segment of the right lower lobe, with increased peripheral vascularity showing supply through the branch of the right bronchial artery. Multiple ill-defined areas of ground glass opacities were noted diffusely and randomly in the right lower lobe, pre- dominantly surrounding the cavitatory lesion, suggesting the possibility of intracavitary haemorrhage with associ - ated adjacent consolidation and alveolar haemorrhages. Well-defined adjacent lung parenchyma showed multiple cysts measuring approximately 6.5 × 5 cm, and emphyse - matous changes in the right lower lobe superior segment may represent congenital cystic adenomatoid malforma - tion (CPAM). A visualised abdominal section showed multiple ill-defined concretions in the bilateral renal pel - vicalyceal system. Her erythrocyte sedimentation rate (ESR) was 10  mm, echo was normal, ejection fraction (EF) was 64%, left ventricular systolic (LV sys) function was good, and tricuspid valve regurgitation was trivial. Her coagulation profile result showed prothrombin time (Pt) -14.5, control (MNPT) -14, and INR-1.04. Bronchos - copy (Olympus ® BF-P240 Flexible Bronchoscope) was performed during menstruation. Bronchoscopy was done when her menses were ongoing under local anaesthesia (lignocaine 4%) to identify and locate the bleeding site of CH. The bronchoscope was entered through the nasal Fig. 1 Chest X-ray of the patient showed thin-walled (thickness 2.8 mm) cavitatory lesion (3.4 × 3.5 cm) right lower zone with radio-opacity lower part of the cavity Page 3 of 8 Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 passage. Pharynx, vocal cord, trachea, and carina were normal. However, active bleeding was seen (Fig.  3, video) at the right superior segment (B6a segment). The bleed - ing lesion of CH was thus identified. Bronchoscopy went uneventful; hence, no intervention was required. Bron - cho alveolar lavage (BAL) was collected and subjected to acid-fast bacillus (AFB), fungal, and gram staining. BAL was also tested for tuberculosis and malignancy. In all three staining results, tuberculosis plus malignancy tests were negative. AFB, bacterial, and fungal cultures of BAL were also done, which were also found to be nega - tive. Cystic airway disease, or cystoid adenoma, was thus ruled out, and diagnosis of CH was confirmed. Counsel - ling for the patient and her relatives was done. Hormonal therapy was not acceptable to the patient; hence, bronchial artery embolisation (BAE) was chosen as a treatment regime (Fig.  4). After BAE, hemoptysis stopped, and her health was stable. She was discharged with prescribed drugs, that is, antacids, antifibrinolytics, haemostatic agent, and antibiotics. There was no episode of CH till 2 years post-procedure. Recently, hemoptysis recured after a gap of 2  years. The severity of hemoptysis was milder as compared to previous episodes before BAE. The amount of bleeding was reduced to one-fourth (20–40  ml) of that in earlier times. A gynaecologist at our hospital was consulted for examining the abdominal and pelvic regions to check for concurrent pelvic endometriosis, which could be developed or was already developed. Her sonography report showed a normal uterus and endometrium. Both the ovaries and abdomen were normal too. Cyproter - one (2  mg) + ethinyl estradiol (0.035  mg) combination pill along with tranexamic acid (500 mg) tablet was pre - scribed for controlling hemoptysis episodes. After taking medicine for 2  months, catamenial hemoptysis gradu - ally ceased.  Side effects related to HT were reported by her which included swelling and pain in both legs with elevated ESR (52) and CRP (11.83) level which subsided with medications.

Hemoptysis is a dreadful and distressing symptom that is associated with several respiratory ailments. It is com - monly found in the cases of tuberculosis (TB), pneu - monia, bronchitis, lung cancer, bronchiectasis due to cystic fibrosis, COPD, etc. Hemoptysis also occurs due to pulmonary endometriosis (PE). PE can result in cata - menial pneumothorax (73%), catamenial hemothorax Fig. 2 Plain and contrast-enhanced MDCT chest with pulmonary angiography with 128-slice MDCT scanner showed well-defined cavitary lesion showing air-fluid level with high-density content in the superior segment of right lower lobe with increased peripheral vascularity showing supply through the branch of right bronchial artery. Multiple ill-defined areas of ground glass opacities are noted diffusely and randomly in right lower lobe predominately surrounding the cavitatory lesion Fig. 3 Active bleeding is seen through bronchoscopy in the right lower lobe superior segment (B6a) of the patient’s lung Page 4 of 8Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 (14%), catamenial hemoptysis (7%), and pulmonary nodules (6%) [6]. CH is a rare form of lung disease that is difficult to diagnose (refer to Table  1 for diagnostic approaches applied to CH by various medical fraterni - ties). It is usually suspected when no other underlying cause of recurrent hemoptysis is noted. In order to dif - ferentiate CH from other forms of hemoptysis, a clini - cal correlation concurrent with the menstrual cycle is needed. The diagnosis of such cases could be done by CT scans synchronised with the menstrual cycle during hemoptysis, which in turn helps in detecting the lesion and also ruling out any other reason for hemoptysis [7]. As reported by Kim et al. [5], the ground glass opacities predominantly appear on thorax CT during CH. Other findings that could be included are nodular lesions, well- defined opacities, bullous formations, and thin-walled cavities [6]. In our patient, the chest CT scan images have shown complex fluid-filled cystic lesions with few air foci in the superior segment of the right lower lobe and mul - tiple other small cystic areas with ground glass opacity in the right lower lobe. Our observation correlates with the other reported findings, which confirm that usually lung lesions are confined to the lower lobes of the right lung [5]. There are possibilities of misdiagnosis when CT and chest X-Ray manifestations are not done during menstruations and due to non-specificity of image find - ings. The bronchoscopy examination utilised in this case was fruitful, as the causative lesion was identified during hemoptysis, and BAL was efficiently collected too to test and discard other causes of hemoptysis. At times, there is a limitation in the utility of bronchoscopy for CH. It shows normal findings mainly when the location of the lesion is not known, when it is not performed during menstruation and hemoptysis, or when the lesion is situ - ated in the distal parenchyma [8]. Chest X-Ray, CT scan, and bronchoscopy were utilised efficiently during menses to conform CH diagnosis. There are no specific guidelines for the treatment of CH. The summarisation of treatment regimens for CH is represented in Table  2. Treatment modalities that are tested and prescribed include hormonal therapy, medi - cal conservative management, and surgical treatment [12]. Rarely used treatment strategies include bilateral oophorectomies, clomiphene citrate therapy, elexacaftor/ tezacaftor/ivacaftor therapy, photodynamic therapy (PDT), indocyanine green-assisted targeting for minimal invasive surgery, hysterectomy, bilateral salpingoopho - rectomy, and, in rare cases, lung transplantation. Hor - monal therapy includes gonadotropin-releasing hormone agonists, progestational drugs, oral contraceptives, and danazol, which work by suppressing the endometrium. These drugs are effective yet come with heavy side effects [17]. High cost of the drug further adds financial burden to the patients. Moreover, its effect ends when the dose is discontinued and leads to a recurrence of the symptoms [5]. It is also not advisable for patients who are planning Fig. 4 Bronchial artery embolisation (BAE) procedure done in the catamenial hemoptysis patient. A Active lesion was seen before BAE. Bronchial artery angiogram showing blush from the lesion. B Right bronchial artery cannulated for embolisation. C Right pulmonary artery angiogram to look for feeding vessel (if any). D. Post embolisation image. BAE was successfully performed Page 5 of 8 Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 Table 1 Tabular representation of diagnostic procedures for catamenial hemoptysis and related observational content and associated limitations Sr. no Diagnostic tools Observe for Limitations Remarks Reference 1 Clinical characteristics - Hemoptysis during menstruation - Woman of reproductive age - Presence of endobronchial ectopic or intrathoracic endometrial tissue - Other causes of hemoptysis should be ruled out - Check for pelvic endometriosis - History of gynaecological or obstet- ric procedures like any pelvic surgery or abortion procedure - Test for increased cancer antigen (CA 125) - Heightened suspicion is required for CH diagnosis - Non-specific physical examination - Unremarkable auscultation - History of gynaecological or obstetric procedures like induced abortion could lead to CH - Smokers have more chances for CH Kim CJ et al. [5] Jang HI et al. [9] Kim JH et al. [10] 2 Chest CT scan - Ground glass opacities - Consolidation - Nodule - Ill- or well-defined opacities - Thin-walled cavities - Bullous formations - The size of the active lesion either reduces or disappears between menses -Located mostly in right lung field - If done on non-menses day, then lesion site and other specifications would be non- or less-visible - Non-specific imaging and laboratory findings - Chest CT should be performed during the first 2 days of menstrua- tion to discover pulmonary haemor- rhage, and with volumetric acquisition technique and thin (1–2 mm) sections, because the lesions can be very small - Comparison of serial CT scans helps in detection and determination of CH- causing factor - To avoid excessive radiation expo- sure in young women, CT should be performed using a low-tube current adjusted to the patient’s body size, without intravenous contrast administra- tion, and limited to the region of interest on follow-up Suwatanapongched T et al. [11] Shin SP et al. [12] Kim CJ et al. [5] Kim JH et al. [10] 3 Bronchoscopic examination - Help in localisation of bleeding lung segment or lobe - Beneficial if lesion is present in mucosa of large bronchi - Beneficial if bleeding site is superficial – Beneficial if done during menstruation - Bronchial wash could be used for ruling out microbial infection and malignancies - Distal parenchymal lesion could not be detected - Non-experienced examiner/clinician could not recognise the suspicious mucosal lesion Shin SP et al. [12] Azizad-Pinto P et al. [13] 4 Invasive tools (VATS) - Direct visualisation of the diaphrag- matic section and lung - Shows larger masses - Shows violet and brown endometrial deposits - Higher diagnostic accuracy - Can show perforation on the surface of the diaphragm - Invasive resection could lead to com- plications - Selection of ‘fit-for-surgery’ patients should be done carefully - Localisation of lesion is important for the success of the surgery Kim JH et al. [10] Nezhat C et al. [14] Cassina PC et al. [15] 5 MRI - Less radiation exposure than CT - Can differentiate parenchymal from pleural implants - Limited to the study of diaphrag- matic localizations of endometriosis and related hernias - MR imaging typically demonstrates a hyperintense lesion on fat-sup- pressed T1- and T2-weighted images at the pleura or diaphragm, signifying haemorrhage coinciding with menses - MR imaging lacks spatial resolution Cassina PC et al. [15] Azizad-Pinto P et al. [13] Marchiori E et al. [16] Page 6 of 8Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 Table 2 Tabulation of treatment procedures for catamenial hemoptysis and associated advantages and disadvantages Sr. No Treatment type Methodology Advantage Disadvantage References 1 Medical treatments Hormonal suppression of endometrium - Complete remission of endome- triomas and effusions can be achieved with 6 months of therapy, - Less invasive - Can preserve fertility - Hemoptysis in CH recurs in 50% (approx.) patients - Menopausal symptoms may develop - Symptoms recur when medication is stopped -Could not be used for young females seeking pregnancy - Costly drugs - Associated side effects like osteoporo- sis, depression, and hot flashes - The optimal dosage and duration of hormonal treatment remains unde- termined Kim CJ et al. [5], Jang HI et al. [9] Kim JH et al. [10] Shin SP et al. [12] 2 Surgery Video-assisted VATS -Safer - Reduces postoperative analgesic requirements -Shortened hospital-stay - Surgical treatment is considered when: (a) a single TE lesion is identified; (b) the patient wishes to become preg- nant; (c) the patient cannot tolerate the side effects of hormonal therapy; (d) medication fails; or (e) symptoms recur after hormonal cessation - Could not be performed in unfit patients -Could not be done for extensive lesions - Invasive, hence complication could arise - Would be failed if exact location of lesion is missed Kim JH et al. [10] Nezhat C et al. [14] Cassina PC et al. [15] 3 Alternative treatment choice Bronchial artery embolisation - Opted for large amount of hemoptysis - Minimal invasive Possible rare complications are spinal cord injury, esophageal ulceration, stroke, bronchial infarction, and transient chest pain - Chances of recurrence Shin SP et al. [12] Page 7 of 8 Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 a pregnancy. Surgical treatment could be applied in cases where medical treatment either failed or stopped due to associated complications. For example, video-assisted thoracoscopic surgery (VATS), lobectomy, wedge resec - tion, open surgery, and endoscopic laser treatment are such surgical techniques [18]. There are few reports about conservative management techniques as a treat - ment modality, mostly among women of reproductive age [19]. In general, the BAE procedure is mostly used to cure hemoptysis caused by lung cancer, TB, bronchi - ectasis, aspergillosis, or chest trauma for large volume of hemoptysis [12]. Only a few side effects are associated with BAE; otherwise, it is a lifesaving, minimally inva - sive procedure that provides long-term relief and a better life ahead. It is also considered a better option than con - servative management techniques [20]. Moreover, as the patient was reluctant for HT and surgical removal of the lesion, BAE was decided as a treatment regime. CH is a rare disease, and only a few have tried BAE as a treatment option [12]. Usually, follow-up of 3 to 5 months post-pro- cedure was observed in other studies, and if there were negative hemoptysis episodes during menstruation, then it was considered a successful procedure. In our case, the patient did not complain of hemoptysis subsequently for 2  years post-procedure; however, it recurred with the same symptoms but with milder intensity. Hence, follow- up should be done over a longer period of time rather than only for the shorter term. Hormone therapy is necessary for treatment even when surgical removal of the CH lesion is adopted because CH is a hormone-stimulated disorder and therefore could be triggered repeatedly. Since our patient was young, she was reluctant to undergo hor - monal therapy out of fear of associated side effects that might erupt, like menopausal symptoms, and could affect her reproductivity. HT could be used as a preven - tive measure for CH patients if the patient is not plan - ning a pregnancy and if HT suits the patient without complications. Hence, BAE was opted for, but without hormonal therapy. That is why it might be the rea - son for CH recurrence after 2  years. As reported by Channabasavaiah AD et  al., up to 50% of CH patients complained of recurrent hemoptysis when only medi - cal therapy was given [21]. Recently, clinicians have been stressing combined surgical and medical treat - ment strategies as there were better and more effective outcomes. Combining hormonal therapy with surgi - cal treatment (removing endometrial tissue to inhibit estrogen stimulation) ensures the complete therapeutic remedy for CH [13, 22– 24]. For the next phase of CH treatment, BAE could not be performed as the amount of hemoptysis was less. Surgical treatment was deferred as symptoms were milder and the patient was young too. Hence, HT was preferred. The patient had reported subsided CH in the first menstruation episode that gradually stopped in the second-month cycle. Patient’s perspective for CH treatment at our centre states that the patient was satisfied with the BAE as it ceased hem - optysis for 2 years and when it re-erupted the volume of hemoptysis, coughing and degree of breathless - ness was significantly lowered than pre-BAE episodes. Thus, mental and physical disturbances caused by CH subsided simultaneously. Depending on the hormonal treatment and its long-term effect, surgical removal of the lesion combined with hormonal therapy might be planned for a complete recovery from CH. In conclusion, in young female patients, episodes of hemoptysis should be closely monitored, especially during the menstrual cycle, as it could be a case of CH. Radiological techniques used for diagnosis play a cru - cial role in the identification of CH when conducted during menstruation. Similarly, bronchoscopy helps in locating the bleeding site and in collection of BAL to check for any microbial infection and malignancies that rule out other causes of hemoptysis. This case suggests that, in the long term, CH can recur after BAE. Regular, long-term follow-up and vigilance for related symptoms are necessary to be tracked. Failed early medical intervention often directs patients to opt for surgical removal of the active lesion responsible for CH through pulmonary surgical procedures com - bined with medical therapy for an effective outcome. However, hormonal therapy alone could be beneficial too. The selection of treatment procedures should be done according to the clinical symptoms and patients’ necessity to maintain fertility. Abbreviations CH Catamenial hemoptysis CT Chest tomography BAE Bronchial artery embolisation HT Hormonal therapy OPD Out-patient department CVS Cardiovascular symptoms HB Haemoglobin HIV Human immunodeficiency virus HBsAg Hepatitis B surface antigen MDCT Multidetector computed tomography CPAM Congenital cystic adenomatoid malformation ESR Erythrocyte sedimentation rate EF Ejection fraction LV sys Left ventricular systolic Pt Prothrombin time MNPT Mean normal prothrombin type INR International normalised ratio AFB Acid-fast bacillus CRP C-reactive protein TB Tuberculosis COPD Chronic obstructive pulmonary disease PE Pulmonary endometriosis PDT Photodynamic therapy VATS Video-assisted thoracoscopic surgery BAL Bronchoalveolar lavage Page 8 of 8Arbat et al. The Egyptian Journal of Bronchology (2024) 18:50 Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s43168- 024- 00298-7. Additional file 1. Video of the procedure.

We are thankful to Mr. Hemant Balapure for assisting in bronchoscopy and for taking a video of the procedure. We acknowledge Dr. Sandeep Chude (radiologist) for providing the bronchial artery embolization (BAE) procedure images. Authors’ contributions SC wrote the initial draft of the manuscript, editing and literature search. AA, GG, SB, and PD managed the diagnosis and treatment. GG, editing, reviewing, and methodology; AA, review, editing, supervision, and final approval of the manuscript; SB and PD, visualisation investigation, and reviewing. All authors approve the final version of the manuscript. Funding This study received no external funding. Availability of data and material Data and material are available on request from the corresponding author. Declarations Ethics approval and consent to participate This study is ethically approved and due course of consent was taken by our hospital’s ethics committee. Consent for publication Consent for publication has been taken from the patient and will be made available on demand. Competing interests The authors declare that they have no competing interests. Received: 21 May 2024 Accepted: 22 June 2024

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