Polyserositis: Causes and Diagnostic Approach
Primary Etiologies
Neoplastic disease is the most common identifiable cause of polyserositis, accounting for approximately 26-30% of cases, followed by autoimmune diseases (16-17%) and infections (12-13%). 1, 2 However, the etiology remains unknown in over one-third of patients despite thorough investigation. 1, 2
Major Diagnostic Categories
Neoplastic Causes:
- Malignancy represents nearly one-third of all polyserositis cases 1
- In patients with prior cancer history, polyserositis frequently signals disease recurrence (9 of 14 patients in one series) 1
- Elevated pleural lactate dehydrogenase levels are significantly associated with neoplastic etiology 1
Autoimmune/Rheumatologic Diseases:
- Rheumatoid arthritis can present with severe disseminated constrictive polyserositis, particularly in CCPA-positive patients 3
- Systemic lupus erythematosus is a recognized cause 3
- Positive antinuclear antibodies in serum are significantly associated with autoimmune disease as the underlying cause 1
- Increased adenosine deaminase levels in pleural effusion strongly suggest autoimmune etiology 1
Infectious Etiologies:
- Tuberculosis remains an important consideration, though infectious causes are proven in relatively few cases 3, 1
- Post-COVID-19 polyserositis has been reported as a late complication occurring months after initial infection 4
Other Causes:
- Periodic disease (familial Mediterranean fever) 3
- Uremia 3
- Drug-induced (including immune checkpoint inhibitors like nivolumab) 5
- Post-surgical or radiation-related 3
- Asbestos or silicosis exposure 3
Anatomic Distribution
Pleural and pericardial involvement occurs in 83% of polyserositis cases, making this the most common pattern. 1 Ascites represents the third most frequent site of serosal involvement. 1
Diagnostic Approach
Initial Assessment:
- Confirm inflammation of two or more serous membranes via imaging studies 1
- Document that at least one serous fluid is an exudate 1
- Obtain fluid samples from affected sites for comprehensive analysis including cell count, biochemistry, cytology, and microbiology 1
Key Laboratory Markers:
- Measure serum antinuclear antibodies (positive results favor autoimmune disease) 1
- Check pleural fluid adenosine deaminase (elevated levels suggest autoimmune etiology) 1
- Assess pleural lactate dehydrogenase (elevated levels associated with malignancy) 1
- Test for rheumatoid factor and cyclic citrullinated peptide antibodies if rheumatoid arthritis suspected 3
- Measure C-reactive protein for inflammatory activity 3
Imaging Studies:
- Transthoracic echocardiography to assess pericardial effusion size, location, and hemodynamic impact 6
- CT imaging to evaluate all serosal spaces and identify underlying structural abnormalities 3
Clinical Pitfalls
Critical Considerations:
- Idiopathic cases (unknown etiology) most frequently present with pleural and pericardial involvement and often resolve spontaneously 1
- Constrictive polyserositis can develop, particularly in rheumatoid arthritis, requiring surgical intervention (subtotal pericardectomy) 3
- Drug-induced polyserositis from immune checkpoint inhibitors requires immunosuppressive treatment with variable response to high-dose IV steroids 5
- Hemorrhagic vasculitis and thromboembolic complications can occur concurrently, complicating anticoagulation decisions 3
Treatment Principles
For Inflammatory/Autoimmune Polyserositis:
- First-line therapy includes NSAIDs plus colchicine for pericarditis-associated effusions 6
- Corticosteroids (metipred) serve as second-line therapy for contraindications or first-line failure 6, 3
- Methotrexate may be added for rheumatoid arthritis-related cases 3
- Plasmapheresis can be considered in refractory autoimmune cases 3
For Neoplastic Polyserositis:
- Treatment targets the underlying malignancy 1
For Idiopathic Cases: