Legionella pneumophila pneumonia with rhabdomyolysis and myocarditis diagnosed by paired bronchoalveolar lavage fluid and blood metagenomic sequencing: a case report

Technical Summary: Legionella pneumophila Pneumonia with Rhabdomyolysis and Myocarditis Diagnosed by Paired mNGS

Problem Statement
Legionella pneumophila is a known cause of severe atypical community-acquired pneumonia, yet its early clinical presentation can be deceptive. While typically recognized as a pulmonary infection, severe cases may initially manifest with dominant extrapulmonary symptoms—such as high fever, diffuse myalgia, gastrointestinal distress, and neurologic abnormalities—while respiratory symptoms remain mild or absent. This atypical presentation often leads to delayed diagnosis and inappropriate treatment. Furthermore, rare but serious complications like rhabdomyolysis and myocarditis are frequently overlooked in the context of Legionella infection, particularly when systemic inflammation overshadows pulmonary signs. Conventional diagnostic methods, including culture, urinary antigen testing (which is limited to serogroup 1), and serology, suffer from technical demands, low sensitivity, or narrow detection scopes, potentially missing the causative pathogen in complex, multisystem cases.

Methodology
The authors present a single case report of a 57-year-old previously healthy male admitted with high-grade fever, diffuse myalgia, dark urine, and mild disorientation, but limited respiratory complaints. Initial workup revealed marked systemic inflammation, rhabdomyolysis (elevated creatine kinase and myoglobin), hepatic injury, and elevated cardiac biomarkers. Chest CT confirmed unilateral pulmonary consolidation.

Given the severity of the pneumonia and the disproportionate multisystem involvement, the diagnostic approach utilized paired metagenomic next-generation sequencing (mNGS) on two distinct specimen types:

1. Bronchoalveolar lavage fluid (BALF): To identify the pulmonary pathogen.
2. Whole blood: To assess for potential systemic involvement or bacteremia.

Conventional microbiological tests (blood cultures, sputum/BALF cultures, viral panels, and Legionella urinary antigen) were performed but yielded negative results. The mNGS data were interpreted in conjunction with clinical findings, imaging, and laboratory background controls. Following pathogen identification, the patient underwent Cardiac Magnetic Resonance (CMR) imaging to evaluate myocardial injury. The patient was treated with targeted anti-Legionella therapy (initially omadacycline, switched to levofloxacin due to adverse effects) and supportive care.

Key Results

• Pathogen Detection: mNGS of the BALF detected 800 sequence reads of Legionella pneumophila. Concurrently, whole-blood mNGS detected 14 sequence reads of the same pathogen.
• Clinical Correlation: The detection of L. pneumophila in both compartments supported a diagnosis of pulmonary infection with probable systemic involvement.
• Cardiac Findings: CMR imaging revealed subepicardial late gadolinium enhancement in the inferolateral wall of the left ventricle, a pattern consistent with myocarditis, in the absence of ischemic heart disease.
• Therapeutic Outcome: After switching to levofloxacin, the patient became afebrile within two days. There was a subsequent gradual resolution of systemic symptoms, normalization of inflammatory markers, reduction in muscle injury enzymes (CK, myoglobin), decline in cardiac biomarkers, and absorption of pulmonary infiltrates on follow-up CT.

Key Contributions
The paper contributes a documented case of severe Legionella pneumophila infection presenting primarily with rhabdomyolysis and myocarditis, where respiratory symptoms were initially non-dominant. It demonstrates the utility of paired respiratory and blood mNGS in establishing a coherent diagnosis when extrapulmonary manifestations are disproportionate to respiratory symptoms. Specifically, the study highlights:

1. The potential for Legionella to cause severe rhabdomyolysis and myocarditis, which should remain in the differential diagnosis for patients with severe systemic inflammation and unexplained muscle or cardiac injury.
2. The complementary value of blood mNGS in suggesting systemic spread when BALF mNGS confirms the pulmonary source, even when conventional cultures are negative.
3. The importance of early pathogen recognition to guide targeted antimicrobial therapy in multisystem Legionella disease.

Significance and Claims
The authors assert that this case underscores the necessity of considering Legionella infection in patients presenting with severe systemic inflammation accompanied by rhabdomyolysis or unexplained myocardial injury, even in the absence of prominent respiratory symptoms. They propose that paired mNGS of BALF and blood can serve as a valuable complementary diagnostic tool for selected patients with severe atypical pneumonia and multisystem involvement.

However, the paper maintains a modest tone regarding its broader implications. The authors explicitly state that mNGS should not replace conventional diagnostics (culture, antigen testing, serology) but rather augment them. They acknowledge limitations, including the lack of culture confirmation, the inability of low-read blood mNGS to definitively prove bacteremia, and the absence of endomyocardial biopsy. Consequently, the paper concludes that while paired mNGS provided critical diagnostic information in this specific instance, its general diagnostic value in similar patients requires further clinical observation and validation.