Few studies have reported Legionella sainthelensi infection. It usually presents with respiratory manifestations;[1,2] however, extrapulmonary manifestations are rare. Here, we report an immunocompromised patient with cavitary pneumonia caused by L. sainthelensi with mainly abdominal symptoms and liver function impairment, but without obvious respiratory symptoms.
Written informed consent was obtained from the patient. A 63-year-old male patient with abdominal distension for 10 days was admitted to our hospital. Three days prior, he developed a fever (maximum at 39.8°C). Antipyretics resulted in fever reduction after 24hours. Bipedal edema was later observed. He denied any nausea, vomiting, or diarrhea, but had alcoholic cirrhosis and underwent transjugular intrahepatic portosystemic shunt (TIPS) 4 years ago. Eight years of alcohol abstinence was noted. Two months previously, routine liver and kidney function tests and chest computed tomography (CT) showed no abnormalities. He had concomitant well-controlled hypertension and diabetes, and no recent travel history. Environmental exposure included daily half-hour walks along a river. Family history was unremarkable.
On admission, the patient was afebrile. Body weight and body mass index were 90 kg and 31.4 kg/m2, respectively. Skin jaundice, scleral icterus, liver palms, spider angioma, ascites, and bipedal edema were noted. Remaining physical examination findings were unremarkable.
Leukocyte count was normal with neutrophilia [86%, relative risk (RR): 50%–70%]. C-reactive protein level was elevated (8.54 mg/L, RR: 0.068–8.2 mg/L). Procalcitonin levels were normal. Total bilirubin was elevated (69.7 μmol/L, RR: 3.4– 20.5 μmol/L); aspartate aminotransferase (AST) (161 U/L, RR: 8–40U/L); and alanine aminotransferase (ALT) (546 U/L, RR: 5–40U/L) levels. Serum albumin levels were low (33 g/L, RR: 35–55g/L). Serum electrolyte and creatinine levels were normal. Abdominal magnetic resonance imaging showed that the liver, gall bladder, and portal veins were unchanged from the previous month’s findings, except for increased ascites and the TIPS stent was unobstructed. Routine analysis of ascitic fluid indicated that the total leukocytes was 114 × 106/L, with 74% lymphocytes and 19% neutrophils, albumin level was 40 g/L, and lactate dehydrogenase was 52 U/L. Gram staining and ascitic fluid culture were negative for bacteria and fungi. The patient was diagnosed with a possible biliary system or abdominal infection.
Furosemide for diuresis, glycyrrhizin for hepatoprotective treatment, and empiric piperacillin-tazobactam (4.5 g every 8hours) were administered. On day 3, serum laboratory tests showed normal ALT and AST levels. Chest CT revealed new focal consolidation in the left lung with cavitation [Figure 1A]. On day 4, sputum Gram staining showed no bacteria, and culture findings revealed normal oral flora. The patient refused bronchoscopy. On day 14, chest CT showed only slight consolidation and cavitation improvement [Figure 1B]. Piperacillin-tazobactam was discontinued. Bronchoalveolar lavage (BAL) was performed to determine the etiology of lung infiltration. BAL fluid underwent Gram staining, culture, and screening for common respiratory pathogens using real-time quantitative polymerase chain reaction (PCR). No pathogens were identified. Next-generation sequencing (NGS) by shotgun metagenomics technology examined the blood and BAL fluid. One-hundred-forty-five sequence reads derived from the BAL sample were mapped to L. sainthelensi, which was the closest matched Legionella genome in the reference database [Figure 2]. Five L. sainthelensi sequences were detected in the plasma samples. L. sainthelensi-specific amplification was also detected in the BAL fluid using PCR [Figure 3]. He was diagnosed with a lung infection secondary to L. sainthelensi. Antibiotics were shifted to 400 mg moxifloxacin once daily. After 14 days of intravenous therapy, chest CT revealed significant resolution of the pulmonary inflammation [Figure 1C]. The patient was discharged on day 28. Follow-up chest CT 8 weeks after discharge showed a small scar at the previous consolidation and cavitation sites [Figure 1D].
This case presented an elderly immunocompromised man with L. sainthelensi infection. To our knowledge, only 15 cases of L. sainthelensi infection have been reported to date, all of which were mainly presented with respiratory symptoms. The extrapulmonary clinical manifestations have rarely been reported previously. Unique presentations for this case of L. sainthelensi infection included the following: abdominal distention, jaundice, signs of liver cirrhosis, bipedal edema, and liver functional impairment; pulmonary consolidation and cavitation via chest CT. Our study may expand knowledge on clinical manifestations of this uncommon pathogenic infection.
The patient was well until 2 months prior to admission. Previous routine tests showed normal serum biochemical indexes and chest CT. Thus, we attributed his abdominal distension and abnormal liver function results secondary to L. sainthelensi infection. The mechanism of extrapulmonary manifestations is unknown but may either be toxin-mediated or secondary to direct tissue invasion.[4,5] Predominant abdominal symptoms could be secondary to his previous alcoholic liver cirrhosis, which may have rendered his liver susceptible to infection. Immunodeficiency caused by this condition may also explain the radiographic appearance of cavitation.
Diagnostic laboratory tests include strain isolation by culture, urinary antigen assay (L. pneumophila subgroup 1 only), serology, and detection of Legionella nucleic acid. Culture remains the gold standard for diagnosis, but few laboratories can grow a pure Legionella culture due to required growth conditions. Urine antigen testing permits early diagnosis but is specific to L. pneumophila serogroup 1. Identification by serologic methods are common, but these antisera are not commercially available. PCR assays for the Legionella DNA gene have been reported to be highly sensitive and specific, with the potential to detect all known Legionella species; however, a commercial kit is unavailable in our hospital.
NGS is a culture-independent technology utilized in microbiology research. NGS makes it possible to detect different types of microorganisms, especially atypical pathogens. Here, conventional clinical microbiological diagnostic methods for pathogens were negative, while NGS demonstrated that L. sainthelensi was the causative pathogen. PCR verification was confirmatory and showed specific amplification of L. sainthelensi sequences.
Delayed therapy for Legionella infection has been associated with increased mortality. Azithromycin and fluoroquinolones are the preferred drugs for Legionnaires’ disease. Because of the patient’s cirrhotic liver, we administered moxifloxacin to treat the patient’s L. sainthelensi pneumonia, which provided immediate disease resolution.
We noted several limitations. First, the case lacked culture isolates and antisera tests to confirm L. sainthelensi. Second, sources of L. sainthelensi were not identified.
This case indicates that L. sainthelensi infection can present unique extrapulmonary manifestations. NGS allowed efficient diagnosis and guided appropriate therapeutic management for rare pathogens. We recommend combining NGS with conventional diagnostic methods to further expand the diagnostic efficacy of identifying pathogenic organisms, especially rare pathogens in immunocompromised patients.
This work was supported by grants from the Innovation Groups of the National Natural Science Foundation of China (81721002).
Xin Yuan and Fanglin Meng were responsible for the clinical treatment of the patient, contributed to interpreting the results, and drafted the manuscript. Xinting Yu acquired data, conducted laboratory tests, and drafted the manuscript. Changqing Bai conceived the work and revised the manuscript. Rui Jia acquired data and revised the manuscript. Fanping Meng and Fu-sheng Wang contributed to interpreting the results and revised the manuscript. Junliang Fu conceived and designed the work, contributed to interpreting the results, drafted and revised the manuscript. All authors approved the final version.
Conflicts of Interest
Editor note: Fu-Sheng Wang is the Editor-in-Chief of Infectious Diseases & Immunity. The article was subject to the journal’s standard procedures, with peer review handled independently by this editor and his research group.
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