A Rare Combination of Legionella ARDS and Pulmonary Embolism: A Case Report

Abstract

Legionnaires’ disease is a severe atypical pneumonia caused by Legionella pneumophila, an aerobic gram-negative bacillus acquired through inhalation of aerosolized contaminated water. Although venous thromboembolism (VTE) has been reported in association with severe infections, its occurrence in Legionella pneumonia remains uncommon and has been hypothesized to be related to infection-driven endothelial injury and systemic inflammatory activation. We report a case of a 38-year-old male with alcohol use disorder and chronic pancreatitis who presented with severe hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS) secondary to severe necrotizing Legionella pneumonia. Imaging demonstrated multifocal pneumonia with cavitary changes and a subsegmental pulmonary embolism in the left lower lobe. The patient met criteria for ARDS based on the 2023 Global Definition of ARDS. He was treated with targeted antibiotic therapy and anticoagulation, later transitioned to oral therapy, and discharged on room air in stable condition. This case highlights the occurrence of pulmonary embolism in the setting of severe Legionella pneumonia and ARDS. While chronic pancreatitis and critical illness are recognized prothrombotic conditions, infection-related hyperinflammation and endothelial dysfunction may have further contributed to thrombotic risk. Clinicians should maintain a high index of suspicion for pulmonary embolism in patients with severe Legionella pneumonia who develop unexplained or disproportionate hypoxemia.

Introduction

Legionnaires’ disease is a severe, atypical pneumonia caused by Legionella pneumophila, an aerobic gram-negative bacillus acquired through inhalation of aerosolized contaminated water. It accounts for 2–9% of cases of community-acquired pneumonia (CAP) worldwide. Typical risk factors include age over 50, smoking, immunocompromised status, chronic lung disease, and recent exposure to water systems such as hot tubs, plumbing, or cooling towers.¹

Legionnaires’ disease usually presents with fever, chills, headache, muscle aches, cough, and shortness of breath. Other characteristic features include gastrointestinal symptoms (diarrhea, nausea, and abdominal pain), confusion, relative bradycardia, and electrolyte abnormalities, including hyponatremia. One rare complication that has been reported in the literature is venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

While Legionella infection is not traditionally associated with a hypercoagulable state, several case reports have described thromboembolic complications. Proposed mechanisms include infection-related endothelial injury and systemic hyperinflammation, although a causal relationship has not been established. Only a limited number of cases describing pulmonary embolism associated with Legionnaires’ disease have been reported, and the underlying mechanisms remain poorly understood. We report a 38-year-old man with alcohol use disorder and chronic pancreatitis who developed acute respiratory distress syndrome (ARDS) secondary to severe cavitary necrotizing Legionella pneumonia and was found to have pulmonary embolism. Diagnosing concomitant pulmonary embolism in patients with severe pneumonia remains challenging because both conditions share nonspecific clinical manifestations.² This case highlights the importance of considering pulmonary embolism in patients with severe Legionella pneumonia who develop persistent or disproportionate hypoxemia. Although chronic pancreatitis and critical illness likely contributed to thrombotic risk in this patient, infection-related hyperinflammation may have represented an additional mechanism promoting thrombosis.

Case Report

A 38-year-old male patient with a history of alcohol use disorder, iron deficiency anemia, chronic pancreatitis, and recurrent aspiration pneumonia presented with sepsis due to severe pneumonia and acute hypoxemic respiratory failure. He subsequently met criteria for ARDS secondary to cavitary necrotizing Legionella pneumophila pneumonia and was found to have a concomitant pulmonary embolism. On arrival in the emergency room (ER), he was severely hypoxic and was placed on a non-rebreather mask. Initial arterial blood gas obtained while the patient was receiving oxygen via a non-rebreather mask (FiO₂ 90%) demonstrated pH 7.413, PaCO₂ 27.4 mmHg, PaO₂ 88.9 mmHg, and HCO₃⁻ 17.1 mmol/L, corresponding to a PaO₂/FiO₂ ratio of approximately 99. The following day, prior to escalation of respiratory support, repeat arterial blood gas showed worsening hypoxemia with pH 7.420, PaCO₂ 28.7 mmHg, PaO₂ 57.4 mmHg, and HCO₃⁻ 18.2 mmol/L (PaO₂/FiO₂ ratio approximately 64), prompting initiation of heated high-flow nasal cannula. His chest X-ray showed bilateral fluffy opacities and consolidation (Figure 1). Contrast-enhanced computed tomography (CT) of the chest demonstrated multifocal pneumonia with scattered cavitary nodules involving multiple lobes and subsegmental pulmonary embolism manifested by a filling defect in the left lower lobe (Figure 2). Urinary antigen testing confirmed Legionella pneumophila. His PaO₂/FiO₂ ratio was 64, fulfilling the 2023 Global Definition of ARDS based on acute hypoxemia requiring high-flow nasal oxygen and bilateral pulmonary infiltrates.³ In addition to severe respiratory distress, the patient’s laboratory studies demonstrated several abnormalities reflecting severe systemic illness. Iron deficiency anemia may have contributed to reduced oxygen-carrying capacity. Elevated blood urea nitrogen and creatinine were consistent with acute kidney injury, likely reflecting hypoperfusion and evolving multiorgan dysfunction in the setting of severe sepsis, supported by an elevated serum lactate. Elevated AST suggested hepatic injury, likely multifactorial from systemic inflammation and underlying alcohol use disorder (Table 1). The patient’s lactic acid level was elevated at 3.14 mmol/L, reflecting tissue hypoperfusion associated with severe hypoxia and sepsis. His white blood cell count increased from 23.6 ×10⁹/L on admission to 35.7 ×10⁹/L two days later. He was empirically treated with intravenous vancomycin and piperacillin-tazobactam. His blood cultures and respiratory cultures were negative. The patient was eventually transitioned to levofloxacin for a total of 21 days based on recommendations from the Infectious Disease and Pulmonology services because of cavitary pneumonia and concern for pulmonary abscess formation. He was initially started on heparin infusion for pulmonary embolism and then transitioned to oral apixaban after five days. He was discharged home on room air in stable condition, but was subsequently lost to follow-up.

Figure 1.

Chest X-ray: Bilateral patchy infiltrates due to pneumonia.

Figure 2.

Contrast-enhanced computed tomography (CT) scan of the chest. The red arrow indicates a filling defect within the left lower lobe pulmonary artery consistent with pulmonary embolism.

Table 1.

Laboratory Values

Parameter	Patient Value	Reference Range
Na	130 mmol/L ↓	136 – 145 mmol/L
K	3.7 mmol/L N	3.5–5.3 mmol/L
BUN	112.0 mg/dL ↑	6.0–24.0 mg/dL
Creatinine	3.98 mg/dL ↑	0.60–1.20 mg/dL
AST	131 U/L ↑	10 – 36 U/L
ALT	29 U/L N	9 – 46 U/L
Lactic Acid	3.14 mmol/L ↑	0 – 2 mmol/L
WBC	23.60 10*3/uL ↑	3.50–10.50 10*3/uL
Hemoglobin	6.9 g/dL ↓	13.5–17.5 g/dL
MCV	65.5 fL ↓	81.2–95.1 fL
PLT	407 10*3/uL N	150 – 450 10*3/uL
D-dimer	>10.000 ng/mL ↑	<500.0 ng/mL
Procalcitonin	100.78 ng/mL ↑	<0.05 ng/mL
Protime	10.7 seconds N	9.4–12.4 seconds
INR	0.96 N	0.83–1.17

Abbreviations: ARDS, acute respiratory distress syndrome; PE, pulmonary embolism; CAP, community-acquired pneumonia; ER, emergency room; WBC, white blood cells; CT, computed tomography; DVT, deep vein thrombosis; DIC, disseminated intravascular coagulation; TTP, thrombotic thrombocytopenic purpura; VTE, venous thromboembolism; N, normal; ↓, decreased; ↑, elevated.

Discussion

The case illustrates a 38-year-old patient with severe Legionella pneumonia, pulmonary embolism, and cavitary pulmonary lesions. While the patient had underlying risk factors for thrombosis, including chronic pancreatitis, iron deficiency anemia, alcohol use, and tobacco exposure, the development of pulmonary embolism in the setting of severe Legionella pneumonia remains clinically noteworthy. The clinical presentation is consistent with published literature suggesting an association between severe Legionella infection and a prothrombotic state. Several lines of evidence suggest that severe Legionella infection may promote a prothrombotic state through interconnected mechanisms of endothelial damage, activation of coagulation, and hyperinflammation. In an in vitro study, Miragliotta et al showed that Legionella pneumophila induces tissue factor–mediated procoagulant activity in peripheral blood mononuclear cells, supporting the hypothesis that Legionella infection may contribute to a prothrombotic state through activation of the coagulation system.⁴

Furthermore, Chiaraviglio et al demonstrated that L. pneumophila can infect and replicate within cultured human endothelial cells, providing a plausible mechanism by which Legionella infection may promote endothelial dysfunction, thereby facilitating activation of coagulation pathways.⁵

Hyperinflammation and cytokine release may represent another mechanism linking severe Legionella infection to thrombosis. Severe Legionnaires’ disease is characterized by increased levels of multiple proinflammatory cytokines, including IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and IL-17.⁶ In addition, Legionella pneumophila stimulates NF-κB- and MAPK-dependent cytokine production by lung epithelial cells, further amplifying the inflammatory cascade.⁷ Although the precise contribution of these pathways to thrombogenesis in Legionella infection remains incompletely understood, systemic inflammation is known to promote activation of coagulation pathways and endothelial dysfunction.

In severe pneumonia, alveolar and systemic fibrinolysis is impaired through increased plasminogen activator inhibitor-1 (PAI-1) activity and decreased urokinase-type plasminogen activator, shifting the hemostatic balance toward fibrin deposition and thrombus persistence.⁸

Corrales-Medina et al reported that nearly 90% of hospitalized patients with pneumonia exhibit evidence of coagulation activation, including elevated D-dimer, thrombin-antithrombin complexes, and plasminogen activator inhibitor.⁹

These proposed mechanisms are supported by published clinical observations describing thromboembolic complications in patients with Legionella infection. For Legionella infection, several cases have reported thromboembolic complications. Rókusz L. reported a patient with community-acquired pneumonia caused by Legionella pneumophila that was complicated by PE.¹⁰ The patient was successfully treated with levofloxacin and anticoagulation therapy. The PE was not attributed to an underlying hypercoagulable state, as the evaluation excluded thrombophilia and antiphospholipid syndrome.

In a case report by Samman et al, a previously healthy 37-year-old male who developed community-acquired Legionella pneumonia had extensive upper limb DVT.¹¹ The diagnosis of Legionella pneumonia was confirmed through positive direct immunofluorescence testing of bronchial washings. Comprehensive evaluations for hypercoagulable states, including assessments for protein C and S deficiencies, antithrombin III levels, and antiphospholipid antibodies, were all within normal limits, indicating no underlying thrombophilic conditions. The patient responded well to appropriate antibiotic and anticoagulant therapies, with complete resolution of symptoms. The case presented by Segnestam et al described a previously healthy man who was treated with ampicillin and gentamicin for Legionnaires’ disease and subsequently developed DVT followed by PE.¹²

Also, Legionnaries’ disease has been linked to disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP), once more highlighting the potential for severe thrombotic complications in the context of the disease. Gregory et al documented DIC in patients with sporadic Legionnaires’ disease, with thrombocytopenia, elevated fibrin degradation products, and prolonged clotting times.¹³ Additionally, Talebi et al described a case of severe TTP with ADAMTS13 activity <5% occurring in the setting of Legionella pneumonia.¹⁴

No single study has comprehensively characterized the mechanisms linking Legionella infection to thrombosis. Taken together, the available evidence suggests that severe Legionella infection may promote a prothrombotic state through multiple pathways, including activation of coagulation, endothelial injury, systemic hyperinflammation, and impaired fibrinolysis. Importantly, these mechanisms are not unique to Legionella infection and have also been described in severe bacterial pneumonia and ARDS; however, the limited number of reported Legionella-associated thromboembolic cases suggests that this pathogen may represent one clinical setting in which these pathways become particularly relevant.

Along with PE findings, the patient’s CT scan of the chest was significant for cavitary nodules. The patient had no known travel history, no pertinent family history, and a social history that included smoking cigarettes and alcohol use, with no illicit drug use. He worked as a lumberjack for many years. The patient had no known primary immunocompromising disorder, and no specific evaluation for underlying immunosuppression was done. However, he had a history of alcohol use, smoking, and recurrent pneumonia, including aspiration pneumonia. Cavitary necrotizing Legionella pneumonia is a rare but well-recognized complication in immunosuppressed patients and is considered rare in immunocompetent individuals.¹⁵ Alcohol use is a risk factor for both Legionella acquisition and severe disease.¹⁶ Alcohol impairs oropharyngeal flora, blunts cough and gag reflexes, thereby impairing immune function and pulmonary clearance mechanisms.¹⁷ This patient’s history of recurrent pneumonia likely reflects alcohol-related immunosuppression and impaired airway protection, which together create a setting for necrotizing infection.

This case adds to the limited literature describing pulmonary embolism complicating severe Legionella pneumonia and highlights the importance of considering thromboembolic complications in patients with severe Legionella infection. Although the patient had underlying risk factors for thrombosis, including chronic pancreatitis, tobacco use, alcohol use, and iron deficiency anemia, the association between severe Legionella infection, ARDS, and PE raises the possibility that infection-related inflammatory and coagulation pathways contributed to thrombus formation.¹⁸

This manuscript has several limitations. A comprehensive hypercoagulable workup, including testing for inherited or acquired thrombophilia, was not performed. This limitation prevents the complete exclusion of underlying VTE predisposition. Also, the patient’s critical illness, pneumonia, and ARDS represent independent risk factors for thromboembolism. As a single case report, this observation suggests only a possible association between severe Legionella pneumonia and thromboembolism. Further studies are needed to better define the mechanisms underlying thrombosis in severe Legionella infection.

Conclusion

In cases of severe Legionella infection, clinicians should maintain a high index of suspicion for thrombotic complications, particularly in patients with persistent or unexplained hypoxemia. Early recognition and appropriate treatment are essential to reduce morbidity and mortality. Further studies are needed to determine whether severe Legionella infection independently increases thromboembolic risk beyond that associated with systemic infection and critical illness.

Funding Statement

No funding was received for this study.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics

Institutional approval was not required for this publication because it describes a single patient case report.

Consent for Publication

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

Disclosure

The authors report no conflicts of interest in this work.