A Young Man's Mystery Illness: Understanding Leptospirosis and Multi-Organ Failure

Table of Contents

• Introduction: Why This Case Matters
• The Patient's Story: Symptoms and Timeline
• Initial Medical Findings
• Detailed Laboratory Results
• Imaging Studies
• What Could This Be? Differential Diagnosis
• Reaching the Diagnosis: Leptospirosis
• How Leptospirosis is Diagnosed
• What This Means for Patients
• Limitations of This Case
• Patient Recommendations
• Source Information

Introduction: Why This Case Matters

This case from Massachusetts General Hospital illustrates how a healthy young person can develop life-threatening illness from an infection many people haven't heard of. Leptospirosis is rare in New England but can occur when people have exposure to contaminated freshwater environments. The case demonstrates the importance of considering unusual infections when patients present with multiple organ failure, even without typical risk factors like international travel.

The Patient's Story: Symptoms and Timeline

A 37-year-old previously healthy man developed sudden severe illness over a 9-day period. His symptoms began with extreme fatigue, weakness, and sleeping almost constantly. Seven days before admission, he developed high fever (39.4°C or 102.9°F), headache, and severe achiness and stiffness in his arms, shoulders, knees, and legs.

He experienced decreased appetite and nausea but no abdominal pain, vomiting, or diarrhea. Five days before admission, his fever and headache improved, but his muscle achiness increased, and he noticed dark yellow urine. Three days before admission, he sought medical care at an urgent care clinic where tests for COVID-19, RSV, and influenza were negative.

Two days before admission, he returned to urgent care with new yellow discoloration of his skin and eyes (jaundice) and was sent to the emergency department. His partner had also experienced a similar but milder illness with fever, malaise, nausea, and diarrhea that began 7 days earlier and resolved after 4 days.

Initial Medical Findings

On initial emergency department evaluation, the patient had:

• Normal temperature: 36.8°C (98.2°F)
• Low blood pressure: 106/70 mm Hg
• Rapid heart rate: 109 beats per minute
• Normal breathing rate: 18 breaths per minute
• Normal oxygen levels: 100% on room air

Concerning laboratory findings included:

• High white blood cell count: 17,900 per microliter (normal: 4,500-11,000)
• Very low platelet count: 34,000 per microliter (normal: 150,000-400,000)
• Normal hemoglobin: 15.7 g/dL (normal: 13.0-17.0)
• High creatinine indicating kidney failure: 3.0 mg/dL (normal: 0.6-1.4)
• Extremely high total bilirubin indicating liver problems: 15.9 mg/dL (normal: 0.0-1.2)
• Very high direct bilirubin: >10.0 mg/dL (normal: 0.0-0.5)

Detailed Laboratory Results

The patient's complete laboratory data showed multiple abnormalities:

Blood Tests (2 days before admission):

• White blood cells: 17,900/μL (high)
• Neutrophils: 16,100/μL (high)
• Lymphocytes: 500/μL (low)
• Hemoglobin: 15.7 g/dL (normal)
• Platelets: 34,000/μL (very low)
• Sodium: 129 mmol/L (low)
• Creatinine: 3.0 mg/dL (high, indicating kidney impairment)
• Urea nitrogen: 48 mg/dL (high)
• Total bilirubin: 15.9 mg/dL (very high)
• Direct bilirubin: >10.0 mg/dL (very high)

Blood Tests (on admission to Massachusetts General Hospital):

• White blood cells: 21,700/μL (higher)
• Hemoglobin: 10.2 g/dL (low, dropped from 15.7)
• Platelets: 67,000/μL (still low but improved)
• Sodium: 124 mmol/L (very low)
• Creatinine: 3.36 mg/dL (still high)
• Total bilirubin: 26.1 mg/dL (even higher)
• Direct bilirubin: 26.1 mg/dL (extremely high)

Urine Tests showed:

• Large bilirubin
• Moderate blood
• High glucose (250 mg/dL)
• Trace ketones
• Protein (300 mg/dL)

Imaging Studies

Dr. Ryan Chung reviewed the imaging studies:

Chest X-ray: Showed bilateral, predominantly peripheral, patchy opacities in both lungs.

Abdominal Ultrasound: Showed hyperechogenic and prominent portal triads with a "starry sky" appearance but no biliary ductal dilatation or kidney swelling.

CT Scan of Chest, Abdomen, and Pelvis: Revealed multiple concerning findings:

• Multifocal consolidative and ground-glass opacities with tree-in-bud nodularity in both lungs
• Small pleural effusions (fluid around the lungs)
• Enlarged mediastinal and hilar lymph nodes
• No liver lesions, biliary ductal dilatation, or liver/spleen enlargement

What Could This Be? Differential Diagnosis

Dr. William C. Hillmann considered multiple possibilities for this complex presentation:

Non-Infectious Causes:

• Cancer (leukemia or lymphoma) - unlikely due to blood cell patterns
• ANCA-associated vasculitis - an autoimmune condition that can affect multiple organs

Infectious Causes:

Tickborne illnesses:

• Lyme disease - common in New England but doesn't typically cause this severe illness
• Anaplasmosis - can cause severe illness, anemia, and low platelets
• Babesiosis - similar to malaria, can cause severe illness with low platelets and respiratory failure
• Rocky Mountain spotted fever - can cause severe illness with low platelets and liver abnormalities

Fungal infections: Such as histoplasmosis or blastomycosis - unlikely without travel to endemic areas or risk factors.

Viral infections: Epstein-Barr virus, cytomegalovirus, or acute HIV - possible but hyperbilirubinemia would be unusual.

The key unique feature was the severe conjugated hyperbilirubinemia (very high direct bilirubin) without other signs of liver injury, which narrowed the possibilities significantly.

Reaching the Diagnosis: Leptospirosis

Dr. Hillmann ultimately diagnosed leptospirosis, specifically the severe form called Weil's disease. Several factors supported this diagnosis:

• The patient walked his dog daily through woods and along a river
• He recalled multiple insect bites during these walks
• His partner had a similar but milder illness
• The clinical presentation matched icteric leptospirosis: fever, multi-organ failure, acute kidney failure, and conjugated hyperbilirubinemia
• Respiratory failure could result from pulmonary hemorrhage or myocarditis, both complications of leptospirosis

Leptospirosis is a zoonotic bacterial infection (spread from animals to humans) most common in tropical environments but possible in temperate regions like New England. Humans acquire it through contact with urine from infected mammals (often rats) or exposure to freshwater contaminated with urine.

While leptospirosis usually causes mild, self-limited fever, in 10-15% of cases it progresses to severe icteric leptospirosis (Weil's disease) characterized by:

• Fever
• Progressive multi-system organ failure
• Acute kidney failure
• Conjugated hyperbilirubinemia (the mechanism isn't fully understood)
• Possible complications: conjunctival suffusions, pulmonary hemorrhage, and myocarditis

How Leptospirosis is Diagnosed

Dr. Robyn A. Stoddard explained the diagnostic approach for leptospirosis:

Leptospira bacteria are spiral-shaped, gram-negative bacteria that can be detected through various methods:

Timing of testing matters:

• First week of symptoms: Whole blood should be tested using nucleic acid amplification testing (NAAT). Serum should be tested for IgM antibodies, which appear 5-7 days after symptoms begin.
• After first week: Urine becomes the preferred specimen for NAAT. Convalescent serum (from recovery phase) should be tested and compared with acute serum if available.

Testing methods include:

• Microscopic agglutination testing (MAT) - the gold standard but not widely available
• IgM antibody detection assays - more sensitive in acute phase
• Polymerase chain reaction (PCR) testing - detects bacterial DNA

In this case, the patient underwent a liver biopsy which showed inflammatory changes consistent with infection but no specific signs of leptospirosis. Special staining and additional testing were needed for definitive diagnosis.

What This Means for Patients

This case has several important implications for patients:

Leptospirosis can occur in unexpected locations: While traditionally considered a tropical disease, climate change and other factors may be expanding its range into temperate regions like New England.

Freshwater activities carry potential risks: Activities involving freshwater exposure (swimming, kayaking, even walking near rivers) can potentially expose people to leptospirosis if the water is contaminated with animal urine.

Pet owners should be aware: Dogs can carry and spread leptospirosis. Vaccination is available for dogs and is commonly administered in some regions.

Early recognition is crucial: The disease can progress rapidly from mild symptoms to life-threatening multi-organ failure. Early treatment with appropriate antibiotics (like doxycycline) is important.

Limitations of This Case

This single case report has several limitations:

• It describes one patient's experience, which may not represent all cases of leptospirosis
• The diagnosis was challenging and required multiple specialized tests
• Without a known outbreak or clear exposure history, the source of infection remains presumed rather than confirmed
• The case occurred in a major academic medical center with extensive resources that may not be available everywhere

Patient Recommendations

Based on this case, patients should:

1. Be aware of potential risks when engaging in freshwater activities, especially if you have cuts or scrapes that could allow bacteria to enter
2. Seek medical attention promptly if you develop fever, muscle aches, and jaundice after potential exposure to freshwater environments
3. Inform your doctor about any environmental exposures, including freshwater activities, insect bites, or sick pets
4. Consider vaccinating pets against leptospirosis if you live in or visit areas where the disease occurs
5. Practice good hygiene after handling animals or soil that might be contaminated with animal urine

Source Information

Original Article Title: Case 31-2024: A 37-Year-Old Man with Fever, Myalgia, Jaundice, and Respiratory Failure

Authors: William C. Hillmann, MD; Ryan Chung, MD; Amir M. Mohareb, MD; Miranda E. Machacek, MD, PhD; Robyn A. Stoddard, DVM, PhD

Publication: The New England Journal of Medicine, October 10, 2024; 391:1343-1354

DOI: 10.1056/NEJMcpc2402493

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