Can myelodysplastic syndrome (MDS) cause bilateral pleural effusions?

Can Myelodysplastic Syndrome Cause Bilateral Pleural Effusions?

Yes, myelodysplastic syndrome (MDS) can cause bilateral pleural effusions, though this is uncommon and typically occurs through specific mechanisms including malignant pleural involvement, infection, or treatment-related complications.

Primary Mechanisms of Pleural Effusions in MDS

Direct Disease-Related Causes

• Malignant pleural involvement occurs in MDS patients, representing direct infiltration of the pleura by dysplastic cells, though this is less common than in acute leukemias 1, 2.

• Infection is the most frequent cause of pleural effusions in MDS patients (47% of cases), often occurring in the context of neutropenia and immunosuppression 1.

• Non-infectious pulmonary complications can include pleural effusions as part of the spectrum of MDS manifestations, though these remain relatively rare 3.

Extramedullary Hematopoiesis

• In the context of primary myelofibrosis (a related myeloproliferative neoplasm), non-hepatosplenic extramedullary hematopoiesis can lead to pleural effusion, pulmonary hypertension, and other thoracic complications 4.

• This mechanism may occasionally apply to MDS with myelofibrotic features, though it is more characteristic of myeloproliferative disorders 4.

Treatment-Related Causes

Chemotherapy-Induced Effusions

• Azacitidine, a DNA-hypomethylating agent commonly used in MDS treatment, can cause serous effusions including pleural effusions as a rare but recognized complication 5.

• Treatment-related effusions may develop through inflammatory mechanisms or lymphatic obstruction 6.

Transfusion-Related Complications

• Chronic transfusion requirements in MDS patients can lead to iron overload affecting cardiac function, potentially contributing to transudative pleural effusions through heart failure mechanisms 4.

• Monitoring serum ferritin levels and considering iron chelation therapy is recommended for chronically transfused MDS patients to prevent organ dysfunction 4.

Clinical Characteristics and Diagnostic Approach

Presentation Patterns

• When pleural effusions occur in MDS, they may be unilateral or bilateral, with the etiology determining the distribution 1, 2.

• Active disease status is present in 61% of MDS patients who develop pleural effusions, suggesting a relationship between disease burden and effusion development 1.

• Common accompanying symptoms include dyspnea (74%), fever (34%), cough (37%), and chest pain (24%) 1.

Diagnostic Workup

• Thoracentesis should be performed to differentiate between infectious, malignant, and treatment-related causes, as this distinction fundamentally alters management 1, 2.

• Pleural fluid analysis should include cytology, cell count and differential, protein, LDH, glucose, pH, Gram stain, and bacterial cultures (including anaerobic cultures) 7, 1.

• Ultrasound guidance is recommended for all pleural procedures to improve success rates and reduce complications 6.

Safety of Pleural Procedures

• Despite severe thrombocytopenia (platelet count <20 × 10³/µL) being present in 43% of procedures, the complication rate is only 1.9% when platelet counts and coagulopathy are optimized prior to intervention 1.

• This low complication rate supports an aggressive diagnostic approach when pleural effusions develop in MDS patients 1, 2.

Prognostic Implications

• Survival is primarily determined by the response to treatment of the underlying MDS rather than the presence of pleural effusion itself 1.

• Older age, active disease status, and MDS diagnosis are associated with shorter overall survival in patients who develop pleural effusions 1.

• The presence of malignant pleural involvement indicates advanced disease and poor prognosis 8, 2.

Management Algorithm

When bilateral pleural effusions develop in an MDS patient:

1. Perform diagnostic thoracentesis with ultrasound guidance after optimizing platelet count (target >50 × 10³/µL if possible) and correcting coagulopathy 6, 1.

2. Send pleural fluid for comprehensive analysis including cytology, cultures (aerobic and anaerobic), cell count, protein, LDH, glucose, and pH 7, 1.

3. Treat based on etiology:

   • If infectious: initiate appropriate antimicrobial therapy 7, 1
   • If malignant: optimize systemic MDS therapy 1, 2
   • If treatment-related: consider dose modification or supportive measures 5
   • If cardiac-related (from transfusional iron overload): optimize heart failure management and consider iron chelation 4

4. Consider pleural or bone marrow biopsy if the cause remains unclear after initial fluid analysis 2.