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 (combination 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 symptoms have ceased after treatment. Therefore, regular follow-up and close vigilance are crucial requirements.


Background
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 endometrial 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 endometriosis 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 infertility (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 pathophysiology is still not clear.Theories suggested are coelomic 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 lymphatic or hematogenous metastasis during delivery or during pelvic surgeries.All these theories failed to establish a clear mechanism of PE [4].PE is usually characterised by CH and it starts and stops with the menstruation cycle of the patient.Symptoms are variable and indefinite, too.Because of missing diagnoses and also because of differences of opinion related to the selected line of treatment, optimal management of CH is challenging [5].Hormonal therapy, conservative treatment, and surgical 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 identification, diagnosis, and treatment strategies for CH customised 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 expectoration 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 complexity 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 (provisional 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 menstruation.She denied a history of pelvic endometriosis, uterine diseases, bleeding diathesis, or smoking.There was no family history of CH.She was therefore admitted during menstruation for further treatment and management.At the time of admission, she was afebrile with a temperature 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 conscious and oriented.The general condition was moderate, and cardiovascular symptoms (CVS) S1 and S2 were normal.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 contrastenhanced 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 highdensity 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, predominantly surrounding the cavitatory lesion, suggesting the possibility of intracavitary haemorrhage with associated adjacent consolidation and alveolar haemorrhages.Well-defined adjacent lung parenchyma showed multiple cysts measuring approximately 6.5 × 5 cm, and emphysematous changes in the right lower lobe superior segment may represent congenital cystic adenomatoid malformation (CPAM).A visualised abdominal section showed multiple ill-defined concretions in the bilateral renal pelvicalyceal 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.Bronchoscopy (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 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 bleeding lesion of CH was thus identified.Bronchoscopy went uneventful; hence, no intervention was required.Broncho 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 negative.Cystic airway disease, or cystoid adenoma, was thus ruled out, and diagnosis of CH was confirmed.Counselling 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.Cyproterone (2 mg) + ethinyl estradiol (0.035 mg) combination pill along with tranexamic acid (500 mg) tablet was prescribed for controlling hemoptysis episodes.After taking medicine for 2 months, catamenial hemoptysis gradually 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.

Discussion
Hemoptysis is a dreadful and distressing symptom that is associated with several respiratory ailments.It is commonly found in the cases of tuberculosis (TB), pneumonia, bronchitis, lung cancer, bronchiectasis due to cystic fibrosis, COPD, etc. Hemoptysis also occurs due to pulmonary endometriosis (PE).PE can result in catamenial pneumothorax (73%), catamenial hemothorax (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 fraternities).It is usually suspected when no other underlying cause of recurrent hemoptysis is noted.In order to differentiate CH from other forms of hemoptysis, a clinical 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, welldefined 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 multiple 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 findings.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 situated 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, medical 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 salpingoophorectomy, and, in rare cases, lung transplantation.Hormonal 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  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 resection, open surgery, and endoscopic laser treatment are such surgical techniques [18].There are few reports about conservative management techniques as a treatment modality, mostly among women of reproductive age [19].In general, the BAE procedure is mostly used to cure hemoptysis caused by lung cancer, TB, bronchiectasis, 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 invasive procedure that provides long-term relief and a better life ahead.It is also considered a better option than conservative 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-procedure 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, followup 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 hormonal 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 preventive measure for CH patients if the patient is not planning 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 reason 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 medical therapy was given [21].Recently, clinicians have been stressing combined surgical and medical treatment strategies as there were better and more effective outcomes.Combining hormonal therapy with surgical treatment (removing endometrial tissue to inhibit estrogen stimulation) ensures the complete therapeutic remedy for CH [13,[22][23][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 hemoptysis for 2 years and when it re-erupted the volume of hemoptysis, coughing and degree of breathlessness 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 crucial 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 combined 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.

Fig. 1
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

Fig. 2 Fig. 3
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. 4
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

Table 1
Tabular representation of diagnostic procedures for catamenial hemoptysis and related observational content and associated limitations

Table 2
Tabulation of treatment procedures for catamenial hemoptysis and associated advantages and disadvantages