What are the common drugs, viruses, and autoimmune diseases that can cause pleuritis?

Common Causes of Pleuritis: Drugs, Viruses, and Autoimmune Diseases

The most common causes of pleuritis include medications like amiodarone, methotrexate, nitrofurantoin, and bromocriptine; viruses such as influenza, coxsackievirus, and cytomegalovirus; and autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and granulomatosis with polyangiitis. 1

Drug-Induced Pleuritis

Common Medications

• Cardiovascular drugs:

  • Amiodarone: Can cause pleuritis, pleurodesis, and pleural effusions through direct toxicity or hypersensitivity mechanisms 2, 3
  • Beta-blockers: May cause lupus-like syndrome with pleural involvement 3
  • Hydralazine: Associated with drug-induced lupus with pleural manifestations 3

• Antirheumatic/Immunosuppressive drugs:

  • Methotrexate: Can cause acute pleuritis, often after the third or fourth high-dose treatment 4, 5
  • Gold salts: Associated with hypersensitivity-induced pleural reactions 3

• Antibiotics:

  • Nitrofurantoin: Causes hypersensitivity-related pleural effusions 3
  • Sulfonamides (including sulfasalazine): Can induce pleural disease 3
  • Erythromycin and ampicillin: Reported to cause hypersensitivity pleuritis 3

• Other medications:

  • Ergot derivatives (bromocriptine): Common cause of drug-induced pleural disease 6, 3
  • Dantrolene: Associated with pleural effusions 6, 3
  • Phenytoin: Can cause hypersensitivity-related pleural reactions 3

Clinical Presentation of Drug-Induced Pleuritis

• Often presents as exudative pleural effusions that may be unilateral or bilateral 7
• Pleural fluid may be clear or hemorrhagic with varied cytological composition 3
• Frequently accompanied by systemic symptoms like fever and malaise 7
• May be associated with pleural thickening, particularly with amiodarone 2
• Pleural fluid eosinophilia may be present and suggestive of drug etiology 7

Viral Causes of Pleuritis

Common Viral Pathogens

• Respiratory viruses:

  • Influenza virus
  • Adenovirus
  • Respiratory syncytial virus (RSV)
  • Parainfluenza virus

• Other viruses:

  • Coxsackievirus and other enteroviruses
  • Cytomegalovirus (particularly in immunocompromised patients) 8
  • Epstein-Barr virus
  • Herpes simplex virus 8
  • Varicella-zoster virus 8

Clinical Presentation of Viral Pleuritis

• Often presents with acute onset of pleuritic chest pain
• May be accompanied by fever, cough, and other viral syndrome symptoms
• Usually self-limiting and resolves within days to weeks
• Pleural effusions, when present, are typically small and reactive
• May occur in the context of viral pneumonia or as an isolated phenomenon

Autoimmune Diseases Associated with Pleuritis

Common Autoimmune Conditions

• Systemic lupus erythematosus (SLE): Pleuritis is a common manifestation and included in diagnostic criteria
• Rheumatoid arthritis (RA): Pleural involvement is a common extra-articular manifestation
• Granulomatosis with polyangiitis (formerly Wegener's): Can involve the pleura
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Microscopic polyangiitis
• Sjögren's syndrome
• Systemic sclerosis
• Mixed connective tissue disease
• Ankylosing spondylitis

Clinical Presentation of Autoimmune Pleuritis

• Often recurrent or persistent
• May be the initial manifestation of the underlying disease
• Frequently associated with other organ system involvement
• Pleural effusions are typically exudative with predominant lymphocytes
• May be accompanied by other serositis (pericarditis, peritonitis)

Diagnostic Approach

For Suspected Drug-Induced Pleuritis:

• Detailed medication history with attention to temporal relationship between drug initiation and symptom onset 7
• Consider drug withdrawal if clinically appropriate before extensive workup 7
• Look for pleural fluid eosinophilia, which may suggest drug etiology
• Improvement after drug discontinuation supports the diagnosis

For Suspected Viral Pleuritis:

• Assess for concurrent viral syndrome symptoms
• Consider viral PCR testing of respiratory specimens or pleural fluid in appropriate cases
• Rule out bacterial superinfection, especially with persistent symptoms
• Most cases are self-limiting and diagnosis is often clinical

For Suspected Autoimmune Pleuritis:

• Screen for systemic symptoms of autoimmune disease
• Appropriate serological testing (ANA, RF, ANCA, anti-CCP, etc.)
• Pleural fluid analysis may show lymphocyte predominance
• Consider rheumatology consultation for comprehensive evaluation

Management Considerations

Drug-Induced Pleuritis:

• Discontinuation of the offending medication is the primary treatment 3, 7
• Most cases improve with drug withdrawal, though pleural thickening may persist 6
• Corticosteroids may be considered for refractory cases 9
• Avoid rechallenge with the suspected medication

Viral Pleuritis:

• Primarily supportive care with adequate pain control
• NSAIDs are first-line for pleuritic pain management 1
• Ensure adequate hydration and rest
• Monitor for complications including secondary bacterial infection

Autoimmune Pleuritis:

• Treatment directed at the underlying autoimmune condition
• NSAIDs for symptomatic relief
• Corticosteroids and immunosuppressive therapy based on the specific disease and severity
• Therapeutic thoracentesis may be needed for large, symptomatic effusions

Pitfalls and Caveats

1. Diagnostic challenges:

   • Drug-induced pleuritis is often a diagnosis of exclusion 6
   • Multiple potential causes may coexist, especially in complex patients

2. Management considerations:

   • Avoid premature attribution to viral causes without excluding other etiologies
   • Consider drug-induced pleuritis before extensive workup in patients on high-risk medications 7
   • Remember that drug-induced pleural disease may occur without parenchymal lung involvement 7

3. Follow-up:

   • Some drug-induced pleural reactions may persist or progress despite drug discontinuation
   • Autoimmune pleuritis may require long-term immunosuppressive therapy
   • Monitor for recurrence, especially with autoimmune etiologies