Author + information
- Tijs Bringmans, MDa,∗∗ (, )
- Inne Vanreusel, MDb,∗,
- Adrien Coquilhat, MDb,
- Stef Derwa, MDc,
- Sabrina H. van Ierssel, MD, PhDd,
- Dina De Bock, MDc and
- Constantijn Franssen, MD, PhDa
- aDepartment of Cardiology, Antwerp University Hospital, Antwerp, Belgium
- bDepartment of Internal Medicine, University of Antwerp, Antwerp, Belgium
- cDepartment of Cardiovascular and Thoracic Surgery, Antwerp University Hospital, Antwerp, Belgium
- dDepartment of General Internal Medicine, Antwerp University Hospital, Antwerp, Belgium
- ↵∗Address for correspondence:
Dr. Tijs Bringmans, Department of Cardiology, Wilrijkstraat 10, 2650 Edegem, Belgium.
This report describes the case of extrapulmonary tuberculosis complicated by esophageal perforation, pneumopericardium, and pericardial abscess formation. The case illustrates the difficulty in diagnosing extrapulmonary tuberculosis, as the occurrence of tuberculosis is rare in the developed world. The appropriate treatment strategy and 6-month follow-up results are discussed. (Level of Difficulty: Advanced.)
- extrapulmonary tuberculosis
- mediastinal tuberculosis
- tuberculous esophageal perforation
- tuberculous pericardial abscess
Tuberculous pericarditis is prevalent in developing countries and it is the most frequent cause of pericarditis (1). In contrast, tuberculosis accounts for only approximately 4% of pericarditis disease in developed countries (2). This paper presents a rare case of combined esophageal and pericardial tuberculosis, complicated by esophageal perforation, pneumopericardium, and pericardial abscess formation.
• Esophageal perforation is a rare presentation of tuberculous gastrointestinal tract infection and should be considered especially when B-symptoms and mediastinal adenopathies are present and there is no evidence of other (malignant) causes.
• Tuberculous pericarditis should always be a differential diagnosis for effusive pericarditis, especially if a “porridge-like” echo-dense pericardial collection is seen.
• The combination of multiple diagnostic tools is necessary to increase the diagnostic yield for tuberculosis.
• Therapy should consist of 4-fold tuberculostatic treatment in combination with high-dose corticoid therapy to decrease the likelihood of constrictive pericarditis as a late complication, at least if HIV reaction is negative.
A 58-year-old white male with suspected esophageal perforation was referred to the authors’ tertiary care hospital. Symptoms had started 5 months earlier with progressive exertional dyspnea, cough with colorless expectorations, night sweats, and anorexia with a weight loss of approximately 10 kg in a month. On clinical evaluation, bilateral fine inspiratory lung crepitations were noted. Laboratory findings showed no signs of inflammation. Positronemission tomography-computed tomography (PET-CT) scans demonstrated an interstitial lung pattern with irregular noduli in the left upper and lower lobe, thickened interlobar septations, and extensive hypermetabolic mediastinal lymphadenopathies. Cytological analysis of samples obtained by endobronchial ultrasonography-transbronchial needle aspiration (EBUS-TBNA) showed no signs of malignancy, lymphoma, or tuberculosis. Hence, the pulmonary abnormalities were considered postinfectious, and ambulatory follow-up was arranged.
Three months later, fever with raised inflammatory parameters occurred. PET-CT demonstrated a left-sided pleural effusion and a large pericardial effusion. Echocardiography showed signs of pericardial tamponade for which an urgent pericardiocentesis was performed. Bacterial and mycobacterial cultures remained negative, as were multiple staining tests for acid-fast bacilli. Pericardial fluid sampling showed a 1% monoclonal B-cell population without abnormalities on peripheral blood analysis. Antinuclear antibodies were present (1:400 dilution), and differentiation was negative. Antinuclear cytoplasmatic antibodies were slightly positive (1:40 dilution). Empirical broad-spectrum antibiotic therapy was initiated, after which symptoms receded, and the patient was discharged.
Readmission occurred 2 months later because of recurrent fever. Blood cultures were positive for Prevotella melaninogenica, a commensal bacterium of the digestive tract. CT scan demonstrated an extensive pneumopericardium, signs of mediastinitis, a large right-sided pleural effusion, and a thickened distal esophagus without fistulation (Figure 1). An esophageal rupture was suspected for which the patient was referred to the authors’ hospital.
On admission, the patient was hemodynamically stable with minor need for supplemental oxygen. Clinical evaluation showed cachexia and bibasal inspiratory lung crepitations. There were no enlarged lymph nodes palpable.
The patient was an active smoker (43 pack-years) and was known to have chronic obstructive pulmonary disease Gold classification 2/A. He consumed 4 units of alcohol per week and denied illicit drug use. He had no contact history for tuberculosis or occupational risk factors. However, 2 years previously, he had traveled to the Republic of Cabo Verde (western Africa) on a holiday at a resort. Serological testing for HIV was negative.
Malignancy of the distal esophagus, nonmalignant distal esophageal ulceration and perforation; mediastinal lymphoproliferative disease, iatrogenic mediastinitis after EBUS-TBNA; sarcoidosis; autoimmune disease; extrapulmonary tuberculosis.
Because malignancy of the distal esophagus was the most probable cause at the time, an upper gastrointestinal tract endoscopy was performed, which showed a large ulceration in the distal esophagus and cardia of the stomach with signs of esophageal perforation but macroscopically not suspicious for malignancy. Radiographic imaging after contrast injection near the ulcer cavity showed a paraesophageal collection without fistulation. Bronchial endoscopy revealed no abnormalities. After 1 week of conservative measurements, adequate healing of the ulcus was seen on endoscopy. There were no signs of malignancy on biopsy samples.
Upon revision of the echocardiographic images, an echo-dense “porridge-like” pericardial collection was noted (Figure 2, Video 1). Differential diagnosis consisted of a postinfectious exudative collection, a primary pericardial malignancy (e.g., angiosarcoma), lymphoproliferative disease, and tuberculous pericarditis. A surgical pericardial biopsy was performed in which a subxiphoidal incision was made with dissection of a 2- × 2-cm pericardial flap, which appeared inflamed (1-cm thick) and very adherent to the myocardium. Microscopic examination revealed chronic granulomatous inflammation with necrosis. Staining for acid-fast bacilli was negative.
PET-CT revealed new large pericardial hypodense and hypermetabolic structures (maximum diameter, 62 mm) (Figure 3). At this time, a QuantiFERON-TB Gold (QIAGEN, Germantown, Maryland) enzyme-linked immunosorbent assay (ELISA) test came back positive. Additional polymerase chain reaction (PCR) analysis for Mycobacterium tuberculosis (MTB) of the pericardial and esophageal biopsies were positive as well, which led to the diagnosis of tuberculous pericarditis and esophagitis.
GeneXpert (Cepheid, Sunnyvale, California) testing of MTB for rifampicin resistance (MTB/RIF) was negative, therefore a classic 4-fold tuberculostatic scheme consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide was initiated. In addition, high-dose corticoid therapy was started with a slow dose tapering scheme (starting dose, 60 mg of prednisone, with dose halved every 4 weeks).
Follow-up after 2 months was favorable, with a resolution of B-symptoms and improvement of exercise tolerance. CT showed regression of the pericardial collections and thickening (Figure 4B). On the basis of the satisfactory evolution, a 2-fold therapy with rifampicin and isoniazid was continued. CT at 6 months showed complete resolution of the pericardial collections, regression of mediastinal lymphadenopathies (Figure 4C), and no signs of constriction on echocardiography. Tuberculostatic treatment was halted after a total of 6 months of therapy.
Extrapulmonary tuberculosis is rare in the developed world, and the simultaneous occurrence of tuberculous pericarditis and esophagitis is even rarer. This case illustrates the problematic diagnosis, as earlier test results for tuberculosis were negative. Other causes were therefore explored, of which malignancy appeared to be the most probable cause. This hypothesis was driven mainly by the unexplained mediastinal hypermetabolic lymph nodes, the thickened distal esophagus, and the pericardial monoclonal B-cell population. Because the endoscopic appearance of the distal esophagus was not suspicious for malignancy, a surgical biopsy of the pathological pericardium was performed. The chronic granulomatous inflammation with necrosis raised the suspicion of tuberculosis, but acid-fast staining was negative. The ELISA test and the PCR analysis of the pericardial biopsy eventually led to the diagnosis of extrapulmonary tuberculosis.
After multidrug resistance was excluded, a standard-of-care regimen of 4-fold tuberculostatic therapy was started that lasted for 2 months, followed by isoniazid and rifampicin therapy for a total of 6 months (2). Longer regimens have previously shown no clinical benefit and may lead to increased costs and risk of poor compliance (3). Concurrent treatment with corticoids is recommended by the European Society of Cardiology in HIV-negative cases to reduce the risk of constrictive pericarditis (2), which generally occurs within 6 months after presentation.
Combined pericardial and esophageal tuberculosis can be challenging to diagnose, especially in nonendemic regions when the index of suspicion is rather low. One should actively exclude tuberculous disease with multiple diagnostic tools, especially if no other diagnosis is found. With adequate therapy and patient compliance, an excellent clinical response can be obtained.
The authors thank our patient for permission to publish the case. The corresponding author would also like to thank Inne Vanreusel, Adrien Coquilhat, and Stef Derwa for co-writing the manuscript, and Dr. Van Ierssel, Dr. De Bock, and Dr. Franssen for their supervision and remarks.
↵∗ Drs. Bringmans and Vanreusel contributed equally to this work.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviation and Acronyms
- computed tomography
- endobronchial ultrasonography-transbronchial needle aspiration
- enzyme-linked immunosorbent assay
- human immunodeficiency virus
- Mycobacterium tuberculosis/rifampicin
- polymerase chain reaction
- positron emission tomography
- Received August 27, 2019.
- Accepted October 24, 2019.
- 2020 The Authors