Rhabdomyolysis and Acute Kidney Injury Associated With Acute Legionella Infection

Introduction

Legionnaires’ disease, caused by the bacterium Legionella pneumophila and related Legionella species, is acquired through inhalation of contaminated water aerosols from sources such as hot tubs, cooling systems, decorative fountains, and grocery produce misters. The disease typically presents as an acute pneumonia with cough, dyspnea, and fever as predominant symptoms, classically accompanied by diarrhea. A wide range of extrapulmonary manifestations are well-documented, including neurologic deficits, hyponatremia, acute kidney injury, and elevated liver enzymes [1]. Uncommon complications, such as rhabdomyolysis and hypertriglyceridemia, have also been described in case reports [2,3]. However, the simultaneous occurrence of rhabdomyolysis, acute kidney injury (AKI), and hypertriglyceridemia in a patient with Legionella infection is rare.

This case report describes a patient who presented with severe rhabdomyolysis and AKI, who was also found to have Legionella pneumonia and hypertriglyceridemia. This atypical presentation highlights the diverse and potentially life-threatening systemic sequelae of Legionella infection and underscores the importance of a broad differential diagnosis and early recognition of these unusual complications to optimize patient management and outcomes.

Case Report

A 34-year-old man with no past medical history presented to the emergency department (ED) with severe muscle cramps. He had been in good health until 3 days prior to admission, when he developed painful muscle spasms in both lower extremities while he was sitting and watching television. He stated that the muscle cramps persisted overnight and gradually worsened, subsequently involving his upper extremities. This was followed by generalized weakness that became progressively debilitating. On review of systems, he reported experiencing diarrhea the day before symptom onset. He also endorsed fever, chills, 2 episodes of vomiting, and dark-colored urine over the subsequent 2 days. He denied any trauma, falls, physical exertion, seizures, new medications, prolonged exposure to heat, and any significant past medical, surgical, or family history. He reported drinking about 40 oz. of beer daily, but had abstained from alcohol for the past 3 days, following the onset of his muscle cramps. He endorsed daily cannabis use via disposable vaping devices but denied cigarette smoking or use of other substances. He was not taking any prescribed or over-the-counter medications.

Upon arrival at the ED, he had a temperature of 37.7°C, heart rate of 122 bpm, blood pressure of 161/112 mmHg, and normal oxygen saturation on room air. The physical exam was significant for an anxious-appearing male in no acute distress, with mild tremors in his hands upon extension. He was oriented to person, place, and time. Strength was 5/5 in his upper and lower extremities, and deep-tendon reflexes were normal. Laboratory evaluation revealed: WBC 13×109/L, Na 126 mmol/L, K 4.5 mmol/L, ALT 184 U/L, AST 1179 U/L, and serum osmolality 283 mOsm/kg (consistent with pseudohyponatremia); bilirubin, lipase, alkaline phosphatase and lactic acid levels were within normal range. Creatine kinase (CK) was markedly elevated at 163 600 U/L. Serum creatinine was 7.79 mg/dL and BUN 60 mg/dL. A urine drug screen was negative for ethanol and positive for THC. Urinalysis showed a large amount of blood, >500 mmol/L protein, WBC 0–5 and RBC 0-, few bacteria, and negative leukocyte esterase and nitrites.

A chest X-ray demonstrated subtle left basilar airspace opacity without consolidation, suggestive of early pneumonia. CT of the chest, abdomen and pelvis revealed left lower-lobe mixed ground-glass consolidation with subtle central clearing (Figure 1). Significant coronary artery calcification and diffuse hepatic steatosis were also noted. The kidneys were normal in size and appearance. On hospital day 2, the Legionella urine antigen test returned positive; respiratory viral panel, Coccidioides IgG and IgM, HIV, EBV, urine Streptococcus Ag, sputum, and blood cultures were negative. A full myositis panel was sent, including ANA, anti-RNP, anti-Jo-1, myeloperoxidase Ab, serine protease 3 Ab, SSA and SSB (anti-Ro), and PM_Scl 100 Ab, all of which were negative; only the serum aldolase, a nonspecific marker of muscle breakdown, was elevated at 231.0 units/L.

The patient was immediately started on aggressive intravenous (IV) rehydration with normal saline, as well as IV azithromycin for Legionella infection. Despite 3 days of fluid resuscitation, his creatinine levels increased, and he was subsequently started on hemodialysis. At the time of admission, he received a loading dose of phenobarbital for alcohol withdrawal, and his symptoms were subsequently managed with lorazepam as needed. After 2 days of treatment, his withdrawal symptoms improved significantly, and no seizures occurred during hospitalization. Although he had no prior history of hypertension, his systolic blood pressure remained in the low 200 mmHg range, and he was treated with losartan, nifedipine, and carvedilol. Plasma renin and aldosterone levels, TSH, and renal Doppler ultrasound did not demonstrate evidence of secondary hypertension. Of note, a fasting lipid panel showed a total cholesterol of 274 mg/dL, HDL 11 mg/dL, LDL 107 mg/dL, non-HDL 263 mg/dL, and triglycerides of 1173 mg/dl. The CK, AST, and ALT levels decreased gradually throughout his hospital course (Figures 2, 3). On discharge, BUN and creatinine were 78 mg/dL and 10.19 mg/dL, respectively (Figure 4), CK was 5996 units/L, and AST and ALT were within normal limits. Follow-up X-ray imaging showed subtle left basilar opacities, consistent with pneumonia. The patient was discharged home with plans for outpatient hemodialysis. Unfortunately, he was lost to follow-up; thus, information about his long-term outcome is not available.

Discussion

This case report highlights a rare and clinically challenging presentation of Legionella pneumonia, characterized by the simultaneous occurrence of severe rhabdomyolysis, acute kidney injury (AKI), hyponatremia, elevated transaminases, and pronounced hypertriglyceridemia. While Legionella pneumophila is well-known for its capacity to induce a wide spectrum of extrapulmonary manifestations, this particular constellation of concurrent findings in multiple organ systems has not been previously reported.

Legionella with rhabdomyolysis and AKI is associated with significant morbidity and up to a 40% increase in mortality (51% vs 15% without AKI) [2,4]. Proposed mechanisms include direct myotoxicity of bacterial toxins, high-fever–induced muscle damage, hypoxemia, and electrolyte disturbances such as hypophosphatemia [5,6]. Individuals with other predisposing risk factors, such as alcohol or drug use, may be at higher risk [7]. Rhabdomyolysis resulting from alcohol withdrawal seizures is well recognized and was a consideration in our patient, but the timing of his alcohol ingestion with his musculoskeletal symptoms and the absence of seizures made this an unlikely etiology. Rhabdomyolysis due to other substances, such as methamphetamines, cocaine, and, less commonly, synthetic and natural cannabinoids, has been described in the literature [8,9]. In our patient, the use of alcohol and vaping with a combination of THC and synthetic cannabinoids may have heightened his susceptibility to muscle damage and renal injury and contributed to the severity of disease. Vaping may also have been the source of the patient’s infection with Legionella pneumophilia, as has been described in a few case reports [10]. The absence of other known risk factors for Legionnaire’s disease, such as smoking, chronic obstructive pulmonary disease, diabetes, or immunocompromised states, point to vaping as the most likely source of infection in this case.

Legionella-associated rhabdomyolysis carries a high rate of severe, prolonged acute kidney injury requiring hemodialysis, as it did in our patient. While AKI associated with Legionella infection is multifactorial and can occur in the absence of rhabdomyolysis, the extreme elevation in creatinine kinase (CK) and the persistence of AKI despite treatment point to myoglobin-induced acute tubular necrosis (ATN) in this case [11]. Aggressive intravenous fluid resuscitation is the mainstay of treatment.

Another atypical feature of this case was the finding of severe hypertriglyceridemia, at a level above the threshold for hypertriglyceridemia-induced pancreatitis, although pancreatitis was ruled out in our patient. While transient elevations in triglycerides can occur during sepsis due to increased very-low-density lipoprotein (VLDL) production in the liver and impaired lipoprotein lipase activity, the severity of hypertriglyceridemia in this case is unusual for Legionella pneumonia [12]. It is possible that our patient’s hyperlipidemia was chronic and preceded his acute illness, given the incidental findings of coronary artery calcification and hepatic steatosis on CT imaging. The cause of the elevated transaminases was likely multifactorial, but the concomitant decrease in AST and ALT along with CK levels indicate they were mostly of musculoskeletal origin.

This case report adds to the body of literature that demonstrates the multiple clinical manifestations of Legionella pneumophilia. Our patient presented with predominant symptoms of rhabdomyolysis, resulting in severe AKI, and was incidentally diagnosed with Legionella pneumonia and hypertriglyceridemia. The constellation of abnormal findings, coupled with identification of vaping as the presumed source of infection, distinguishes this case from other reported cases of Legionella-induced rhabdomyolysis and AKI. This unique presentation challenges clinicians to be vigilant and thorough in investigating possible causes of non-traumatic rhabdomyolysis and evaluating patients for all the possible systemic complications of Legionella infection.

Conclusions

Legionella infection is an uncommon cause of rhabdomyolysis, which is associated with significant morbidity and mortality. In patients whose history lacks a clear etiology of rhabdomyolysis, it is essential to consider infectious causes in the differential diagnosis, particularly when there are concurrent pulmonary and extrapulmonary findings. Prompt recognition, early treatment of infection, and aggressive supportive care are essential to improve patient outcomes.