Summary
Legionnaires" disease (LD) is a systemic infectious disease caused by Legionella species. It mainly presents with lung involvement. Herein, we present a case with suspected myocarditis associated with LD and review of the relevant literature. An 81-year-old male tourist patient with high fever, cough, imbalance while walking, and confusion presented to the emergency department. The patient was diagnosed with LD based on increased density in the left lower zone on chest x-ray and a positive Legionella urine antigen test. He was administered a combination of claritromycin and levofloxacine on the day of admission. The diagnosis of acute myocarditis was made after worsening of the cardiac functions, ST elevation and troponin I positivity. The patient"s symptoms regressed with antibiotic therapy and the patient was transferred to his home country by ambulance plane ten days after admission. A search of PubMed and Web of Science using the keywords "Legionella and myocarditis" revealed 15 case reports, nine of which were in English and were reviewed. There were three female and six male patients with a mean age of 44 years (range: 32-56 years). Seven were diagnosed with LD by urine antigen testing, one by serological testing and culture, and one by direct fluorescent-antibody staining and culture. Myocarditis was diagnosed by biopsy in two patients and by clinical and laboratory findings in the rest. Myocarditis without existing pneumonia was detected in one case. Electrocardiography abnormalities such as atrial flutter, atrioventricular block, torsade de pointes, sinus tachycardia, QT prolongation, ST elevation, and T wave inversion were detected in seven patients. Ventricle dysfunction on echocardiography and cardiac marker abnormality were detected in all but one of the patients (not tested in one patient). Antimicrobial monotherapy was chosen for three of the cases. One patient died due to myocarditis. In conclusion, myocarditis may develop rarely during the course of LD. Clinical suspicion is essential for the diagnosis. Early diagnosis and appropriate treatment may be life-saving.
Introduction
Legionnaires" disease (LD) is a systemic infectious disease caused by Legionella bacteria which primarily affects the lungs. More than 90% of LD is caused by Legionella pneumophila. Legionella bacteria accounts for approximately 2-15% of communityacquired pneumonia[1, 2]. In LD, involvement of extrapulmonary organs such as heart, liver, kidneys is rare and results from the direct or indirect influence of bacteria (toxins, etc.)[1, 3, 4]. Cardiac involvement in LD may lead to the development of endocarditis, myocarditis, and pericarditis, as well as arrhythmias such as sinus bradycardia, second-and third-degree atrioventricular (AV) block, atrial fibrillation, and premature ventricular contractions. There have also been reports of cases with cardiac involvement in the absence of pulmonary involvement[5, 6]. In this paper, we present our management and follow-up of a case of LD with signs of cardiac involvement and review the related literature.
Case Report
During consultation with the cardiology department while the patient was in the emergency unit, electrocardiography (ECG) showed sinus tachycardia without ischemic changes. Echocardiography (ECHO) revealed an ejection fraction of 60%, normal wall appearance, and biatrial dilatation. On the 4th day of hospitalization, anterior ST-elevation myocardial infarction pattern (Figure 4) was observed, and akinesia in the apical segments was evident on ECHO. Laboratory values were as follows: ALT: 89 U/L, AST 99 U/L, CK: 288 U/L, and troponin 1: 0.054 ng/mL (0-0.023). Coronary angiography could not be performed because the patient and his relative did not consent to the procedure.
The patient"s agitation resolved on the 5th day of hospitalization and oral antibiotic treatment was initiated on the 7th day. The patient"s overall condition improved and his symptoms diminished; on the 10th day of hospitalization, the patient voluntarily returned to his home country by air medical transport. The patient"s spouse and doctor reported that the patient continued to be treated for LD in a hospital in his home country and was discharged on October 27, 2015. The patient recovered after undergoing physical therapy rehabilitation and lived in good health for over two years.
Review of Literature
A literature search of PubMed and Web of Sciences on 1 December 2016 using the keywords "Legionella and myocarditis" yielded 15 articles. The nine cases published in English were analysed and are summarized in Table 1.
Discussion
Criteria for definitive diagnosis of LD are isolation of Legionella bacteria in cultures, positive Legionella urine antigen test, and observing at least a 4-fold increase in antibody titer against L. pneumophila serogroup 1 in paired serology. The Legionella urine antigen test is valuable in LD diagnosis because patients become positive within the first few days of infection; it is not affected by antibiotic use, is easily performed, and provides rapid results. The test has a sensitivity of 70-80% and specificity close to 100%; the sensitivity and specificity rates of the urinary card test are comparable to those of ELISA. The biggest disadvantage of the test is the lack of reliability for species and serogroups other than L. pneumophila serogroup 1[1, 2]. Definitive LD diagnosis was established for our patient upon obtaining a positive Legionella urine antigen result. Legionella bacteria could not be isolated in the sputum culture obtained when the patient was receiving antibiotic treatment. Serologic tests were not used in our case because of their limited benefit in early diagnosis.
Myocarditis is an inflammatory disease of the cardiac muscle which may exhibit different clinical presentations depending on the severity of cardiac involvement (focal, diffused, etc.). It may show wide clinical variability, ranging from mild symptoms to heart failure, cardiogenic shock, arrhythmia, and sudden death. ECHO findings can range from diffused wall motion abnormalities to regional motion abnormalities. Clinical suspicion is essential for the diagnosis of myocarditis. Elevated cardiac biomarkers (such as troponin, CK-MB), ECG changes indicating acute myocardial damage, arrhythmia, and new and unexplained disruptions of cardiac function are also suggestive of myocarditis[16]. Endomyocardial biopsy is the gold standard in diagnosis, but it must be noted that this technique is applicable only in selected cases due to the difficulty and the risk involved.
Of the nine cases identified in our literature review, the male:female ratio was 2:1 and the mean age was 44 years (range: 32-56 years). Seven of the cases exhibited abnormalities on ECG (atrial flutter, AV block, torsade de pointes, sinus tachycardia, prolonged QT, ST elevation, T-wave inversion), and all cases showed ventricular dysfunction on ECHO. Cardiac biomarker abnormalities were reported in eight of the cases. In only two cases, the myocarditis diagnosis was based on cardiac biopsy. In our case, clinical findings were accompanied by elevated troponin I values, newly emergent ST elevation, and akinesia in apical segments on ECHO. Cardiac biopsy was not performed. When observed only in the apical myocardial segments, as in our case, wall motion abnormalities may be indicative of focal myocarditis. ECG abnormalities associated with myocarditis may initially mimic ST-elevation or non-ST-elevation acute myocardial infarction[17]. However, considering how ST-T abnormalities evolve in the course of time, the ECG changes associated with acute myocarditis evolve much slower than those seen with acute myocardial infarction[18]. As in our case, persistence for even a few days without forming pathological Q wave is indicative of acute myocarditis. In cases with ECG and ECHO findings and elevated cardiac biomarkers, stress cardiomyopathy or neurogenic heart syndrome should also be considered in the differential diagnosis. Stress cardiomyopathy is a condition that occurs in patients under severe physical or psychic stress. Findings include apical aneurysm, as well as ECG changes mimicking acute myocardial infarction and cardiac enzyme abnormalities[19]. In our case, the confirmed presence of an etiology (LD) that may cause may cause myocarditis, increased the probability of myocarditis. However, the likelihood of the two conditions co-occurring is even higher.
Combination therapy is usually preferred in cases with severe LD and extrapulmonary organ involvement. Macrolides are administered with rifampicin or a quinolone drug as combination therapy. The duration of treatment is 7-10 days. Treatment should be extended to 14-21 days for cases with severe course, extrapulmonary organ involvement, and immunosuppression[1, 2]. It should be kept in mind that macrolides and quinolones used in the specific treatment of LD may have an arrhythmogenic effect or exacerbate an underlying condition. We preferred a combination of quinolone and macrolide for our patient. Six of the nine cases found in our literature review were also treated with combination antibiotic therapy. Even under appropriate antibiotic therapy, a patient"s clinical condition may deteriorate or increased density may be observed on chest radiography, as in our case. In a case reported by Briceño et al.[7], the patient developed severe left ventricular failure and cardiogenic shock due to repolarization anomaly despite receiving appropriate antibiotic therapy. A mechanical assist device (TandemHeart pVAD) was used briefly to treat cardiogenic shock. Damásio et al.[8] used intra-aortic balloon pump and extracorporeal membrane oxygenation in a patient who developed cardiogenic shock. Only one of the nine cases did not respond to treatment and died.
In conclusion, LD should be suspected in cases of severe community-acquired pneumonia with prominent extrapulmonary symptoms. It is important to be aware that symptoms and findings related to cardiac involvement may be encountered during the clinical course of LD. Clinical suspicion is essential for diagnosis. Early diagnosis and proper treatment of LD may be life-saving.
Ethics
Informed Consent: Consent form was filled out by patient relative.
Peer-review: Externally and internally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: H.E., H.O.E, Concept: H.E., H.O.E, Design: H.E., H.O.E, Data Collection or Processing: H.E., H.O.E, Analysis or Interpretation: H.E., H.O.E, Literature Search: H.E., H.O.E, Writing: H.E.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.
