Incessant pericarditis due to lung cancer and obstructive pneumonia

Abstract

An 83-year-old man was admitted to our hospital with chest and back pain accompanied by a high fever. His electrocardiogram showed ST elevation in the inferior leads, and transthoracic echocardiography revealed a moderate amount of pericardial effusion. Contrast-enhanced computed tomography revealed lung cancer adjacent to the pericardial sac and obstructive pneumonia. Emergent cardiac catheterization was performed; however, no coronary artery occlusion was detected. Based on these findings, a diagnosis of acute pericarditis was made. The patient was treated with colchicine, ibuprofen, and antibiotics. By the third day of hospitalization, his fever, chest pain, pericardial effusion, and ST elevation had improved. However, on the sixth day, his chest pain recurred, ST elevation reappeared, and the pericardial effusion increased. These findings gradually improved with conservative management. Our final diagnosis was incessant pericarditis. As the patient and his family declined invasive treatment, he was discharged on the 28th day of hospitalization under a policy of best supportive care. Incessant pericarditis with rapid alternation between improvement and exacerbation within a short period is considered uncommon. In the present case, the fluctuations in pericarditis were thought to be associated with obstructive pneumonia and pericardial invasion by lung cancer.

Learning objective

• ✓Incessant pericarditis is rare, but some cases of acute pericarditis may follow an incessant inflammatory course.
• ✓In addition to common viral infections, other causes of pericarditis such as obstructive pneumonia and lung cancer should also be considered and investigated.

Introduction

In some cases of acute pericarditis, patients exhibit a persistent inflammatory course, referred to as incessant pericarditis [1]. Acute pericarditis is commonly caused by viruses such as coxsackievirus group B, echoviruses, and adenoviruses, which are also frequent causes of upper respiratory tract infections [2]. Incessant pericarditis is usually attributed to the same viral etiologies, while non-viral causes such as malignancy or other inflammatory conditions are considered rare.

Herein, we report a rare case of incessant pericarditis caused by lung cancer and obstructive pneumonia, in which ST elevation and pericardial effusion showed fluctuation corresponding to the progression and resolution of inflammation.

Case report

An 83-year-old man had been experiencing back pain since early February. Two days after symptom onset, his pain worsened during the night, accompanied by the development of a fever. The back pain worsened when lying down or coughing and was relieved when sitting and leaning forward. He was transported to our hospital by ambulance. His medical history included angina pectoris, hypertension, chronic kidney disease, prostatic hypertrophy, right internal carotid artery occlusion, and cerebral infarction. He had no family history of cardiovascular disease. He had a 58-year history of heavy smoking but no history of alcohol consumption. There was no documented history of autoimmune disease.

On arrival, his body temperature was 39.8 °C. Blood pressure was stable at 133/70 mmHg, and physical examination revealed no signs of shock or low cardiac output. A chest X-ray showed a cardiothoracic ratio of 60 % and bilateral pleural effusions. A twelve‑lead electrocardiogram revealed widespread ST-segment elevations, most prominent in leads II, III, and aVF. And in addition, PR-segment depression was noted in leads II, III, aVF, and V4–V6, which is a classical electrocardiographic feature of acute pericarditis. (Fig. 1A). Laboratory tests showed elevated white blood cell count (13,600 /μL, neutrophil, 82 %; lymphocyte, 11 %) and C-reactive protein (CRP) level (11.56 mg/dL), as well as elevated D-dimer (4.0 μg/mL), but high-sensitivity troponin I was within normal limits (9 pg/mL). The baseline estimated glomerular filtration rate was 26 mL/min/1.73m², corresponding to chronic kidney disease stage G3b (Kidney Disease Improving Global Outcomes). Transthoracic echocardiography demonstrated preserved left ventricular systolic function and circumferential pericardial effusion, with a maximum thickness of 10 mm along the posterior left ventricle. To investigate the causes of those findings, contrast-enhanced chest computed tomography (CT) was performed, which showed pericardial fluid accumulation of approximately 10 mm and no evidence of aortic dissection. A 50-mm mass in the right lower lung lobe in direct contact with the epicardium and obstructed pneumonia were also noted (Fig. 2). A faint pericardial friction rub and jugular venous distension were observed. To rule out acute myocardial infarction or left ventricular rupture, emergency coronary angiography was performed. Moderate to severe three-vessel coronary artery disease was observed, but no coronary occlusion or flow delay indicative of acute myocardial infarction was detected. Based on these findings, acute pericarditis secondary to direct pericardial invasion by lung cancer was suspected.

Fig. 1.

Serial changes in 12‑lead electrocardiogram (ECG). (A) Full 12‑lead ECG at presentation. (B and C) Limb lead ECGs on hospital day 3 and day 6, respectively. (A) Widespread ST-segment elevation is observed, particularly prominent in the inferior leads (red arrows). PR deviation was observed in leads II, III, aVF, and aVR (blue arrows). In (B), this ST elevation has nearly normalized; however, in (C), re-elevation of the ST segment is noted. ST elevation is indicated with red arrows.

Fig. 2.

Contrast-enhanced computed tomography findings at presentation. The left image shows circumferential pericardial effusion with a maximum thickness of 10 mm (red arrows). The right image reveals a 55 mm mass in contact with the pericardium in the left lower lobe, along with distal atelectasis and consolidation suggestive of pneumonia (blue arrow). No signs of dissection are observed in the ascending aorta.

The procedure of pericardiocentesis was not performed because the amount of pericardial effusion was relatively small, and the risk was considered to be high. Treatment was initiated with ibuprofen (600 mg/day), colchicine (0.5 mg/day), and intravenous ampicillin-sulbactam (3 g twice daily). Serum levels of creatine kinase (CK), CK-MB, and troponin I subsequently increased to 783 pg/mL and peaked on hospital day 2. On hospital day 3, CRP levels had decreased to 10.41 mg/dL, ST-segment elevation had almost normalized (Fig. 1B), and the posterior left ventricular pericardial effusion had reduced to 6 mm. However, on day 6, chest pain recurred, ST elevation reappeared in leads II, III, and aVF (Fig. 1C), CRP increased again (35.32 mg/dL), and the pericardial effusion worsened to 13 mm (Fig. 3). These findings suggested a diagnosis of incessant pericarditis rather than typical acute pericarditis. The underlying cause was suspected to be direct pericardial invasion by lung cancer, and the fluctuations in pericardial inflammation were presumed to be related to the course of obstructive pneumonia. It should be noted that this dose was below the European Society of Cardiology (ESC) 2015 guideline recommendation of 800 mg every 8 h (2,400 mg/day). This reduced dose—necessitated by advanced age and renal impairment—may have contributed to insufficient suppression of pericardial inflammation and the development of an incessant course.

Fig. 3.

Serial changes in the acute phase of pericarditis (on admission, hospital day 3, and day 6). The upper panel shows C-reactive protein (CRP) levels, the middle panel shows ST-segment elevation on electrocardiogram (ECG), and the lower panel shows changes in pericardial effusion. The initially elevated CRP, ST-segment elevation, and pericardial effusion observed at presentation improved by day 3 following treatment with colchicine, ibuprofen, and antibiotics, but worsened again on day 6.

LV, left ventricular.

Based on sputum cytology and elevated tumor markers (squamous cell carcinoma: 3.5 ng/mL, CYFRA: 54 ng/mL), the lung cancer was diagnosed as squamous cell carcinoma. Contrast-enhanced CT suggested possible invasion into the right main bronchus, and the clinical stage was considered to be at least stage IIIA. Curative surgery in a single stage was deemed difficult, and a treatment plan aiming to reduce the tumor size with initial chemotherapy and radiotherapy was proposed by the multidisciplinary medical team. However, the patient's performance status was between 2 and 3 on the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) scale, and there was concern that these treatments could further worsen the PS. Finally, the patient and his family declined these options. Following advanced care planning discussions, a policy of best supportive care was adopted. Low-grade fever, elevated CRP levels, and ST-segment elevation on the electrocardiogram persisted, and the CRP level on the 23rd day of hospitalization was 11.04 mg/dL. He was discharged on foot 28 days after admission. Those findings were gradually improved, and at three months post-discharge, CRP was 1.79 mg/dL; chest CT revealed progression of the lung mass but resolution of the pneumonia. He died six months after discharge due to lung cancer. During hospitalization and at three-month follow-up, echocardiography did not reveal findings suggestive of constrictive physiology (e.g. interventricular septal shift, hepatic vein flow reversal, or exaggerated respiratory variation). Clinically, there was no persistent jugular venous distension or hepatomegaly. Thus, no evidence of constrictive pericarditis was observed during the observation period.

Discussion

Although pericarditis was originally classified as “acute,” “relapsing,” or “chronic,” more and more cases that do not respond to standard treatment [non-steroidal anti-inflammatory drugs (NSAIDs) + colchicine] have been reported [2]. Dependence on steroids and immunosuppressive drugs, and a pattern of immediate relapse upon steroid reduction have been observed, and they are now required to be classified as “incessant” (not cured all the time) rather than “relapsing” [1,2]. Clearly defined in guidelines published in 2015 by the ESC, incessant pericarditis is defined as pericarditis that persists without a symptom-free period of 4–6 weeks despite treatment [2]. The etiology of the incessant pericarditis is frequently viral, with pathogens such as coxsackievirus, echovirus, and adenovirus implicated in many cases. However, other causes such as autoimmune diseases, neoplasms, and post-pericardiotomy syndromes can also be involved [2]. Persistent inflammation is believed to result from a combination of immune dysregulation and inadequate suppression of the initial inflammatory response.

Pericardial effusion due to cancerous infiltration of the pericardium is commonly observed; however, reports of cases showing ST-segment elevation caused by malignant pericarditis (without invasion to myocardium) are rare. Kasim et al. reported esophageal cancer induced acute pericarditis and ST elevation without invasion to myocardium [3]. Bijay reported a similar case of ST elevation and lung cancer, and the authors advocated the term “paraneoplastic reactive regional pericarditis” [4]. The authors considered the cause of the ST elevation was due to regional inflammation of pericardium which was previously reported in cases of myocardial infarction [5].

Although incessant pericarditis is a recognized condition, cases with rapid fluctuations in inflammation—characterized by alternating improvement and exacerbation over a short period—have not been previously reported. Regarding infections associated with pericarditis, two relevant cases have been described. Tenenbaum et al. reported a case of hemorrhagic pericarditis caused by chlamydial pneumonia, and another case of acute pericarditis secondary to obstructive pneumonia due to a testicular tumor [6]. Ahmed et al. presented a case of a non-seminomatous extragonadal germ cell tumor manifesting as early pericardial tamponade [7]. These infectious diseases may involve fluctuating inflammatory activity. Obstructive pneumonia, in particular, is a representative condition that can show such fluctuations, potentially triggering recurrent exacerbations and remissions of pericarditis. In our case, the fluctuation of pericardial inflammation was assessed by serial changes in clinical symptoms, serum CRP levels, electrocardiographic findings, and echocardiographic effusion thickness. Possible mechanisms include (i) direct tumor invasion, (ii) inflammatory cytokine release due to obstructive pneumonia, (iii) paraneoplastic immune activation, and (iv) insufficient suppression of inflammation due to low-dose NSAID therapy. Obstructive pneumonia, in particular, may have contributed to pericardial inflammation through contiguous spread of local inflammation from pneumonia to the pericardium, cytokine activation, or bacterial microinvasion. The temporal correlation between the fluctuation of pneumonia and pericardial inflammation supports this link.

Conclusions

Non-viral causes of incessant pericarditis such as lung cancer invasion to pericardium are rare. Moreover, the present case showed an interesting course of improvement-exacerbation of pericarditis due to obstructive pneumonia.

Consent statement

Written informed consent was obtained from the patient for the publication of this case report, including the accompanying images.

Declaration of competing interest

The authors have no conflicts of interest to declare.