Rheumatoid Pleurisy - 10 Marks (MD Exam Answer)

Definition

Incidence

• Walker and Wright found pleural effusions in 17 of 516 RA patients (3.3%) without other obvious cause.
• More common in men (7.9%) than women (1.6%).
• Horler and Thompson: 9 of 180 patients with RA (5%) had unexplained pleural effusion; 15% of men vs. 1% of women.
• Pleuritic chest pain: 28% of men and 18% of women with RA.

Pathological Features

• Parietal pleura: "Gritty" or frozen appearance; slightly inflamed and thickened with numerous small vesicles or granules ~0.5 mm in diameter.
• Visceral pleura: Varying degrees of non-specific inflammation.

• Absence of normal mesothelial cell covering (most constant finding).
• Pseudostratified layer of epithelioid cells with multinucleated giant cells (different from Langerhans or foreign-body type).
• Nodular areas show features of a rheumatoid nodule: palisading cells, fibrinoid necrosis, lymphocytes, and plasma cells - virtually diagnostic.
• Thickened pleura may contain cholesterol clefts.

Clinical Manifestations

• Nearly all patients are >35 years old.
• ~80% are men.
• ~80% have subcutaneous nodules.
• Arthritis typically precedes the effusion by a mean of ~10 years; rarely, effusion precedes arthritis.
• Symptoms: ~50% are asymptomatic; others have pleuritic chest pain, dyspnea; rarely, respiratory failure.
• Chest radiograph: Small-to-moderate-sized effusion (<50% hemithorax), usually unilateral (no side preference); ~25% bilateral; may alternate sides.
• ~1/3 of patients have associated intrapulmonary manifestations of RA.
• PET scans show intense pleural uptake.

Pleural Fluid Characteristics

Cytology

1. Slender elongated multinucleated macrophages (comet/tadpole-shaped cells)
2. Round giant multinucleated macrophages (Fig. 21.2)
3. Granular necrotic background material

Glucose Mechanism

• Thickened pleura limits glucose entry into the pleural space.
• High metabolic activity of the pleural surface consumes glucose rapidly.
• Result: Pleural glucose falls far below serum glucose.
• Raising serum glucose does not raise pleural glucose, but oral urea/IV d-xylose loads do equilibrate - suggesting a selective block in carbohydrate transport.

Associated Finding: Cholesterol

• 21% of rheumatoid pleural fluids contain cholesterol crystals (Ferguson, Naylor).
• Many more have high cholesterol levels (>1,000 mg/dL) without crystals.
• Crystals impart a sheen to the fluid; high cholesterol makes it turbid.

Complication: Concomitant Infection

• Necrobiotic subpleural nodules can break down, creating a bronchopleural fistula.
• Jones and Blodgett: 5 of 10 patients with rheumatoid pleural effusion developed empyema over 5 years.
• Empyemas more common in patients on corticosteroids.
• Always obtain aerobic and anaerobic cultures + Gram stain of centrifuged sediment.

Biopsy

• Closed pleural biopsy has limited role.
• May occasionally reveal a rheumatoid nodule (diagnostic) but usually shows only chronic inflammation or fibrosis.
• Not recommended in typical cases.
• Thoracoscopy or pleural biopsy indicated in atypical cases (no arthritis, or normal pleural fluid glucose) to exclude malignancy and tuberculosis.

Differential Diagnosis from Other High-ADA Conditions

Prognosis

• Favorable: 76% (13/17 patients) had spontaneous resolution within 3 months.
• 1 patient resolved after 18 months; another persisted >2 years.
• One patient developed progressive severe pleural thickening requiring decortication.
• One developed an empyema.

Treatment

1. NSAIDs (aspirin/ibuprofen) for 8-12 weeks initially.
2. Systemic corticosteroids if effusion persists and joint symptoms uncontrolled - some patients respond; no controlled trials available.
3. Intrapleural corticosteroids: Limited evidence; one case responded to 120 mg depomethylprednisolone.
4. Methotrexate: May improve arthritis but can paradoxically cause pleural effusion.
5. Therapeutic thoracentesis: For symptomatic relief.
6. Decortication: For symptomatic patients with thickened pleura causing dyspnea; technically difficult (poor tissue planes, prolonged air leaks); but can substantially improve quality of life.
   • Measure pleural pressure serially during thoracentesis: rapid drop = trapped lung = consider decortication.
7. Bronchopleural fistula/empyema: Managed same as complicated parapneumonic effusion; higher incidence of persistent fistula requiring thoracotomy.

Key Points to Remember (Exam Summary)

• Older male + RA + subcutaneous nodules + pleural effusion = Rheumatoid pleurisy until proven otherwise
• Glucose <20 mg/dL is the hallmark - most characteristic finding
• pH <7.20, LDH >700, RF ≥1:320 in pleural fluid (≥ serum titer)
• Low complement (C3, C4, CH50)
• Pathognomonic cytology: giant elongated multinucleated macrophages + necrotic background
• Cholesterol crystals in 21% (can mimic pseudochylothorax)
• Must rule out empyema when glucose very low
• Natural history mostly favorable with spontaneous resolution
• NSAIDs first; corticosteroids for persistent disease; decortication for trapped lung