A Case of Sudden Confusion and Kidney Failure: Understanding Legionnaires' Disease

Table of Contents

• Case Presentation: A Healthy Man's Sudden Decline
• Initial Examination Findings
• Detailed Laboratory Results
• Imaging Studies
• Differential Diagnosis: What Could Cause This?
• Final Diagnosis: Legionella Infection
• Laboratory Testing Details
• Clinical Implications for Patients
• Source Information

Case Presentation: A Healthy Man's Sudden Decline

A 47-year-old man with no previous medical problems arrived at Massachusetts General Hospital with severe confusion and acute kidney failure. His symptoms began just six days earlier when he developed fatigue and muscle aches (myalgias). Despite feeling unwell, he continued working at his restaurant job for two more days.

Four days before admission, his coworkers noticed mild confusion. On the day of admission, his confusion worsened significantly, and he developed word-finding difficulties and garbled speech. Emergency services were called, and he was transported to the hospital. In the emergency department, he reported feeling hot and short of breath but couldn't provide a complete medical history due to his confused state.

Additional history from family revealed he took ginseng extract and burdock root supplements but no prescription medications. He lived in a converted factory apartment in New England, smoked marijuana occasionally, had smoked cigarettes as a teenager, and drank alcohol infrequently. His family history included a sister with multiple autoimmune conditions including Sjögren's syndrome and nemaline myopathy.

Initial Examination Findings

On examination, the patient had a low body temperature of 35.8°C, elevated blood pressure of 142/78 mm Hg, rapid heart rate of 114 beats per minute, and rapid breathing at 30 breaths per minute. His oxygen saturation was 96% on room air. He appeared anxious and was slow to answer questions, unable to recite days of the week backward, and had difficulty following complex commands.

Notable examination findings included symmetric facial movements, normal cranial nerve function, normal muscle strength and tone, normal sensation and reflexes, and no photophobia (light sensitivity). His mucous membranes were moist, neck was supple, heart sounds were normal, lungs were clear, abdomen was non-tender, and he had no swelling or rash.

Detailed Laboratory Results

The patient's laboratory results revealed multiple abnormalities indicating severe multi-organ involvement:

• Complete Blood Count: Elevated white blood cells at 13,270/μL (reference: 4,500-11,000) with increased neutrophils (12,560/μL) and decreased lymphocytes (240/μL)
• Kidney Function: Severely elevated blood urea nitrogen at 117 mg/dL (reference: 8-25) and creatinine at 13.0 mg/dL (reference: 0.6-1.5)
• Electrolytes: Low sodium (125 mmol/L), high potassium (6.0 mmol/L), low chloride (75 mmol/L), and low carbon dioxide (9 mmol/L)
• Muscle Damage: Extremely elevated creatine kinase at 28,581 U/L (reference: 60-400) indicating severe muscle breakdown
• Liver Function: Elevated aspartate aminotransferase (418 U/L) and alanine aminotransferase (1,272 U/L)
• Inflammation Markers: High C-reactive protein at 220.4 mg/L (reference: 0.0-8.0) and erythrocyte sedimentation rate at 69 mm/hr (reference: 0-13)
• Other Findings: Elevated ferritin (5,064 μg/L), d-dimer (>10,000 ng/mL), lactic acid (2.3 mmol/L), and lactate dehydrogenase (1,334 U/L)

Urinalysis showed blood (3+), glucose (1+), protein (2+), and elevated red and white blood cells. Toxicology screens were negative for common drugs and substances.

Imaging Studies

Chest X-ray revealed an opacity in the right lower lobe. CT scan of the head was normal. CT scan of the chest, abdomen, and pelvis showed consolidation in the right lower lobe with minimal adjacent ground-glass opacity but no lymphadenopathy (swollen lymph nodes).

Three hours after arrival, the patient's condition worsened with fever (38.2°C), increased breathing rate (45 breaths/minute), and decreased oxygen saturation (89% on room air), requiring supplemental oxygen at 6 liters/minute.

Differential Diagnosis: What Could Cause This?

The medical team identified two main problems: severe muscle breakdown (rhabdomyolysis) without trauma or exertion, and lung consolidation with systemic inflammation. The kidney failure, metabolic acidosis, liver injury, and confusion were considered consequences of these primary issues.

Several possible causes were considered and evaluated:

• Nemaline Myopathy: Ruled out because this genetic condition typically presents differently with gradual weakness rather than acute symptoms
• Toxins or Supplements: Unlikely as his supplements (ginseng and burdock) aren't known to cause rhabdomyolysis, and toxicology screens were negative
• Inflammatory Myopathies: Less likely given the acute presentation rather than gradual progression
• Infections: Strongly considered given the combination of respiratory and systemic symptoms

Among infections, influenza was considered but ruled out by negative testing. HIV and fungal infections like Aspergillus were possible but less likely given the presentation. Bacterial infections, particularly Streptococcus and Legionella, emerged as the most likely causes given the combination of pneumonia, muscle breakdown, and neurological symptoms.

The patient's residence in a converted factory building was particularly relevant, as Legionella bacteria often thrive in complex water systems of large buildings.

Final Diagnosis: Legionella Infection

The medical team concluded that Legionella infection (Legionnaires' disease) was the most likely diagnosis based on several factors:

• The combination of pneumonia with muscle breakdown (rhabdomyolysis) is more common with Legionella than other infections
• Neurological symptoms like confusion are characteristic of Legionnaires' disease
• Laboratory findings including low sodium, high inflammatory markers, and liver enzyme elevations are typical of this infection
• The patient's residence in a converted factory building provided a potential source of exposure

The diagnosis was confirmed when a Legionella urinary antigen test returned positive.

Laboratory Testing Details

Legionella pneumophila is a gram-negative bacterium commonly found in freshwater environments, particularly in warm water systems like cooling towers, plumbing systems, and complex water arrangements often found in large buildings. The bacteria grow best in temperatures between 20-42°C and thrive in biofilms within water systems.

Infection typically occurs when contaminated water is aerosolized and inhaled. The doctors suspected the patient was exposed through the ventilation system in his converted factory apartment. Despite being a generally healthy 47-year-old without typical risk factors (like older age, smoking history, or immunocompromise), he developed severe disease, suggesting he inhaled a large quantity of bacteria.

Diagnostic testing for Legionella includes urinary antigen tests (which detect specific bacterial proteins in urine) and specialized culture techniques. The urinary antigen test is particularly valuable as it provides rapid results and remains positive even after antibiotic treatment has begun.

Clinical Implications for Patients

This case illustrates several important points for patients:

• Legionnaires' disease can affect healthy individuals and present with unusual symptoms beyond typical pneumonia, including confusion and muscle breakdown
• Environmental exposures in building water systems can cause serious illness
• Early recognition and appropriate antibiotic treatment are crucial for recovery
• Patients with persistent fatigue, muscle aches, and confusion along with respiratory symptoms should seek medical attention promptly

Treatment typically involves specific antibiotics that effectively target Legionella bacteria. In this case, the patient received intravenous ceftriaxone and azithromycin initially, which cover both Legionella and other potential bacterial causes of pneumonia.

Prevention involves proper maintenance of water systems in large buildings, including regular cleaning and temperature control to prevent bacterial growth. Individuals at higher risk (older adults, smokers, those with weakened immune systems) should be particularly aware of these potential exposure risks.

Source Information

Original Article Title: Case 29-2024: A 47-Year-Old Man with Confusion and Kidney Failure

Authors: Sachin J. Shah, M.D., M.P.H., Melissa C. Price, M.D., and Sanjat Kanjilal, M.D., M.P.H.

Publication: The New England Journal of Medicine, September 19, 2024

DOI: 10.1056/NEJMcpc2402492

This patient-friendly article is based on peer-reviewed research from Massachusetts General Hospital case records.