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 for cell count, biochemistry (LDH, protein, glucose, adenosine deaminase), cytology, and culture 1
Laboratory Markers with Diagnostic Significance:
- Antinuclear antibodies: positive results significantly associated with autoimmune disease 1
- Adenosine deaminase in pleural fluid: elevated levels suggest autoimmune etiology 1
- Pleural LDH: increased levels significantly associated with neoplasm 1
- Rheumatoid factor and CCPA antibodies: consider in patients with arthralgia or minimal arthritis 3
- C-reactive protein: markedly elevated in rheumatoid-associated cases 3
Imaging Studies:
- Transthoracic echocardiography for pericardial effusion assessment 1
- Chest CT for pleural evaluation 1
- Abdominal imaging for ascites characterization 1
Clinical Pitfalls
Critical Diagnostic Challenges:
- Constrictive polyserositis can mimic liver cirrhosis when presenting with ascites, hepatomegaly, and cholestasis 3
- Sequential rejection of diagnoses (tuberculosis, cirrhosis, autoimmune hepatitis, vasculitis) may occur before reaching correct diagnosis 3
- Drug-induced polyserositis from immune checkpoint inhibitors requires high clinical suspicion and immunosuppressive treatment 5
- Unknown etiology cases most frequently present as pleural-pericardial involvement and often resolve spontaneously 1
Treatment Considerations
For Autoimmune-Related Polyserositis:
- Corticosteroids (metipred/methylprednisolone) form the cornerstone of therapy 3
- Methotrexate may be added for rheumatoid-associated cases 3
- Plasmapheresis can be considered in refractory cases 3
- Surgical intervention (subtotal pericardectomy) may be necessary for constrictive pericarditis 3
For Drug-Induced Cases:
- High-dose intravenous corticosteroids are required, though response is variable 5
- Discontinuation of the offending agent (e.g., immune checkpoint inhibitors) 5
For Infectious Etiologies: