Where could Mycoplasma pneumoniae infection be located if mycoplasma antibodies are elevated but chest computed tomography (CT) shows no pulmonary involvement?

Potential Locations of Mycoplasma pneumoniae Infection with Elevated Antibodies and Clear Chest CT

Mycoplasma pneumoniae infection can manifest in various extrapulmonary sites despite elevated antibodies and a clear chest CT, most commonly affecting the central nervous system, liver, skin, joints, and hematologic systems.

Extrapulmonary Manifestations of Mycoplasma pneumoniae

Mycoplasma pneumoniae is traditionally associated with respiratory infections, but can cause significant disease outside the lungs even when pulmonary imaging is normal. These extrapulmonary manifestations occur through several mechanisms:

Central Nervous System

• Encephalitis
• Aseptic meningitis
• Polyradiculitis
• Cerebellar ataxia
• Myelitis
• Progressive weakness/neuropathy

The central nervous system is likely the most common site of extrapulmonary involvement 1. Up to 7% of hospitalized patients with M. pneumoniae may have CNS symptoms, which can occur through direct invasion, neurotoxin production, or immune-mediated mechanisms 1.

Musculoskeletal System

• Rhabdomyolysis with elevated creatine kinase
• Diffuse joint pain and myalgias
• Polyarthritis

These manifestations can be severe and may require immunomodulatory therapy in addition to antimicrobial treatment 2.

Hematologic System

• Acute thrombocytosis (important diagnostic clue)
• Hemolytic anemia
• Mononuclear syndrome with atypical lymphocytes

Acute thrombocytosis during weeks 1-2 of illness should suggest M. pneumoniae in patients without zoonotic exposure 3.

Hepatobiliary System

• Acute hepatitis with elevated transaminases
• Abnormal prothrombin time

Cases have been reported with significant liver involvement without pulmonary manifestations 4.

Dermatologic Manifestations

• Erythema multiforme
• Various rashes

Other Systems

• Cardiac arrhythmias
• Gastrointestinal manifestations (loose stools/diarrhea)
• Nonexudative pharyngitis

Diagnostic Approach

When suspecting extrapulmonary mycoplasma infection:

1. Serologic testing: Look for elevated M. pneumoniae IgM and IgG antibodies
2. Cold agglutinin titers: Present in 75% of M. pneumoniae infections; higher titers (>1:64) more suggestive 3
3. Complete blood count: Watch for acute thrombocytosis, which can be a key diagnostic clue 3
4. Liver function tests: Check for elevated transaminases if hepatitis is suspected
5. Neurological evaluation: If CNS symptoms are present
6. Advanced imaging: Consider CT or MRI of affected organ systems

Treatment Considerations

For confirmed extrapulmonary M. pneumoniae infection:

1. Antimicrobial therapy: Macrolides (first-line), doxycycline, or fluoroquinolones
2. Immunomodulatory therapy: Consider for severe manifestations, particularly neurological
   • Corticosteroids
   • Intravenous immunoglobulin (IVIG) for progressive weakness/neuropathy 2
3. Supportive care: Hydration and symptomatic management

Clinical Pearls and Pitfalls

• Pearl: Acute thrombocytosis in a patient with negative respiratory findings but positive M. pneumoniae serology strongly suggests extrapulmonary infection 3
• Pitfall: Failing to consider M. pneumoniae in patients with neurological, hepatic, or hematologic abnormalities without respiratory symptoms
• Pearl: Extrapulmonary manifestations may occur even with negative initial serologic tests; consider repeat testing if clinical suspicion is high 2
• Pitfall: Assuming that a clear chest CT excludes M. pneumoniae infection

Remember that the pathogenesis of extrapulmonary complications of M. pneumoniae infection remains incompletely understood, but likely involves direct invasion, neurotoxin production, or immune-mediated mechanisms 5, 1.