Talc-induced pericardial granulomatosis after recurrent pleurodesis: a rare cause of incessant pericarditis-case report.

A 41-year-old woman was diagnosed with catamenial pneumothorax. She presented recurrent episodes of right pleuritic chest pain and dyspnoea after the onset of menstruation, followed by spontaneous resolution within days. For achieving definitive symptom control, she received hormonal therapy in combination with surgical approach via video-assisted thoracoscopy surgery (VATS). Six months after initial diagnosis, she underwent first surgical procedure in which repair of diaphragmatic defects and talc pleurodesis were performed. Subsequent recurrences of pneumothorax prompted a second VATS for mechanical and talc pleurodesis along with partial parietal pleurectomy. Six months later, a third VATS was performed, involving paraseptal emphysema resection and talc pleurodesis. One month after last surgical procedure, our patient presented with oppressive central thoracic pain, spreading to neck and jaw, with no fever or abnormalities detected in laboratory tests or electrocardiogram. Physical examination was normal, with no pericardial friction rub. A transthoracic echocardiography revealed hyperrefringent, thickened pericardium and mild pericardial effusion located predominantly in the anterior wall of the right ventricle (RV) and apex (see Supplementary material online , Video S1 ), accompanied by hyperechoic images suggestive of fibrinous strands; no data of haemodynamic compromise were identified. Acute pericarditis was diagnosed, and she commenced anti-inflammatory therapy with colchicine (0.5 mg/day) and acetylsalicylic acid (500 mg every 8 h) for three months. Although there was a partial clinical improvement, a small residual pericardial effusion persisted. Autoimmune and infectious causes of pericarditis were also ruled out. During the following 24 months, the patient continued to have episodes of oppressive central thoracic pain radiating to the neck, along with dyspnoea during medium exertion. Symptoms worsened in relation to physical activity or emotional stress. Dyspnoea of a respiratory cause was ruled out. Cardiac magnetic resonance ( Figure 1 ) and computed tomography ( Figure 2 ) were performed ruling out effusive–constrictive and pericardial endometriosis, revealing right pleural nodular thickening and mild pericardial effusion. No significant echocardiographic changes were detected. Ineffective therapeutic attempts to control pain were made with amitriptyline, gabapentin, carbamazepine, right stellate ganglion, and thoracic epidural blocks. Thirty-one months after first episode of AP, after undertaking moderate physical exertion, our patient experienced sudden clinical deterioration characterized by intense pericardial pain. This was accompanied by an increase in pericardial effusion with fibrinous strands, up to 15 mm in the anterior and lateral walls of the RV (see Supplementary material online , Video S2 ), and up to 20 mm in aortic recess (see Supplementary material online , Video S3 ). These findings suggested new episode of AP ( Figure 3 ). Blood analysis and electrocardiogram showed, again, no pathological findings. During following four months, step medical therapy was initiated with colchicine (1.5 mg/day), indomethacin (150 mg/day), anakinra (200 μg/day), and prednisone (50 mg/day). As adjuvant therapy for pain control, two left stellate ganglion blocks were performed, resulting in an effective but temporary response. Cardiac magnetic resonance (CMR) phase contrast imaging (on month 30 th of the timeline disease). ( A ) Cine (steady-state free precession sequence) CMR of four-chamber view. Mild pericardial effusion in apex (arrow). ( B ) Late gadolinium enhancement CMR image. Mild pericardial effusion with no delayed enhancement of the pericardium (asterisks indicate layers of the pericardium). Cardiac computed tomography (on month 44 th of the timeline disease). ( A ) Axial-oblique view. Pericardial effusion in the superior aortic recess (red asterisk). Nodular pleural thickening of the right hemithorax (red arrow), due to previous talc-induced pleuritis. ( B ) Sagittal view. Retrosternal linear calcification (blue arrow). Two-dimensional transthoracic echocardiography that shows pericardial effusion (blue arrows) with fibrinous strands (red arrows). ( A ) Parasternal short axis. ( B ) Four-chamber view. ( C and D ) Modified parasternal long axis focused on ventricular apex and ascending aorta, respectively. Due to persistent clinical symptoms and pericardial effusion, surgery was indicated. An anterior inter-phrenic pericardiectomy was performed. The intraoperative findings only revealed clear pericardial effusion and normal pericardium appearance. However, the anatomopathological examination findings confirmed the presence of talc-induced pericardial foreign body granulomas in both the pericardium and mediastinal fat samples ( Figure 4 ). The patient experienced progressive improvement in her clinical condition, returning painless to normal daily activities six months after intervention. Echocardiographic assessment at the three-month and six-month follow-up showed no residual pericardial effusion. Haematoxylin–eosin stain of the biopsy sample. ( A ) Pericardium and mediastinal fat showing foreign body granuloma (giant-cell reaction). ( B ) 20× magnification. Talc crystal (arrows) surrounded by multinucleated giant cells.

Dr Ana Coca-Perez (MD, PhD) is a paediatric intensivist with more than 15 years of medical experience, actually working in the PICU at Ramón y Cajal University Hospital (Madrid, Spain), where daily work involves management of paediatric patients with medical and surgical conditions, including patients with complex congenital heart diseases (main area of her interest apart from point-of-care ultrasonography). Over the last 14 years, she has actively participated in projects of international cooperation for the development of sustainable paediatric cardiac surgery programmes in low-resource countries, with both medical support and on-site training.

The most frequent complication after an episode of acute pericarditis (AP) is recurrent or incessant pericarditis, reported in ∼15–30% patients. 1 Management of relapsing pericarditis still represents a challenge for clinicians. According to the 2015 European Society of Cardiology Guidelines for diagnosis and management of pericardial diseases, primary treatment includes colchicine and non-steroidal anti-inflammatory drugs, with low-dose prednisone considered a secondary option due to its potential to promote recurrences. Several drugs, such as immunoglobulin, aziatropine, or anakinra, have been employed as a third-line treatment, eventually reducing the corticosteroid doses. 1 However, there is still a group of patients who remains unresponsive to conventional treatment, significantly compromising their quality of life. Although pericardiectomy remains controversial due to perceived risks of mortality and morbidity associated with this extensive surgery, as well as the limited data on the recurrence rates, some studies have suggested that is safe and effective in reducing subsequent relapses for this subset of patients. 2

Timeline of the disease course in months. CP, catamenial pneumothorax; GnRh, gonadotropin-releasing hormone agonist; VATS, video-assisted thoracoscopy surgery; AP, acute pericarditis; ASA, acetylsalicylic acid.

Talc-induced pericardial granulomatosis after pleurodesis is a rare entity that has, so far, only been described in experimental animal models. 4 , 7 Onset of pericardial symptoms after a procedure of chemical pleurodesis should make us suspect this entity. Due to the local and chronic inflammation nature of the disease, conventional medical treatment, according to current guidelines for pericardial diseases management, may not be appropriate, 1 and early surgery should be considered.

This rare case of incessant pericarditis was a diagnostic and therapeutic challenge. The finding of talc-induced pericardial granulomas in the anatomopathological examination played a key role in the aetiological diagnosis. The absence of previously described cases, the non-specific clinical presentation with no associated abnormalities detected in laboratory tests (due to the local and non-systemic nature of the inflammation), were the main limitations in our approach to this case, with a definitive diagnostic delay of several months which led to the inappropriate use of medication and invasive procedures in order to manage the patient’s chronic chest pain. Despite long evolution of symptoms, it was not until the development of incessant pericarditis that pericardiectomy was indicated. Talc is the cheapest and most effective sclerosing agent for pleurodesis, as shown in human and animal studies. 3 Talc induces an intense chemical pleuritis that effectively obliterates the pleural space. 4 It has been used effectively in the treatment of recurrent spontaneous pneumothorax, showing good tolerance with no long-term sequelae. The most common side effects are usually mild and self-limiting, such as pain, fever, or air leaks. 3 , 5 While more severe complications, such as respiratory failure and acute respiratory distress syndrome are infrequent, fatal cases have been published. 6 Besides, talc can be absorbed through the lymphatic vessels of the parietal pleura entering systemic lymphatic circulation, or can migrate through leaks in the pleural cavity, with talc deposition into the lungs or other extrapleural organs. 4 , 7 This latter pathway appeared to be the underlying mechanism of disease in our patient. Similarly to lung talc-related granulomatosis, which has been described after instillation of intrapleural talc, or after intravenously injected talc-containing drugs in parenteral drug abusers (PDA), 8 the deposition of talc in the pericardium causes the same giant-cellular reaction. Although there are anecdotal cases of talc-induced myopericarditis described in PDA, due to intravenous injection of crushed tablets containing talc, 9 extrapleural talc dissemination to mediastinum and pericardium following pleurodesis, until now, has only been described in autopsies and experimental animal models. 4 , 7 Catamenial pneumothorax is a relatively rare clinical entity with a high recurrence rate despite a combination of surgical and hormonal approach. 10 In our patient, the past medical history of multiple intrapleural procedures and pleural thickening from previous talc-induced pleuritis contributed to pleural leakage and talc migration to pericardium, leading to chronic inflammation. The presentation of pericarditis as foreign body giant-cell reaction explains the partial medical response achieved with conventional pharmacological treatment. Although pericardiectomy remains controversial, its ‘off-label’ indication was pivotal in our approach to this case. It not only enabled definitive diagnosis but also provided symptomatic relief and a marked improvement in the quality of life of our patient.