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Rheumatoid Arthritis: Cardiac & Pulmonary Involvement

Diagnosis (Dig) and Differential Diagnosis (DD)

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CARDIAC INVOLVEMENT

Spectrum of Direct Cardiac Manifestations

• Pericardial effusions occur in up to 50% by echocardiography but are usually asymptomatic. Long-standing disease can progress to fibrinous or constrictive pericarditis.
• The most common cause of death in RA is cardiovascular disease. Patients have significantly increased coronary artery disease and heart failure (approximately 2x the general population rate), even after controlling for traditional risk factors like smoking, hypertension, and obesity. Chronic inflammation is the primary driver, compounded by glucocorticoid use and physical inactivity.
• Congestive heart failure (both systolic and diastolic dysfunction) occurs at ~2x the background rate.
• Cardiac MRI is sensitive for subclinical myocardial involvement.

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Differential Diagnosis of RA Cardiac Findings

• Other CTD: SLE (most common CTD-pericarditis), systemic sclerosis, MCTD
• Viral/idiopathic pericarditis
• Tuberculous pericarditis (especially important in endemic areas; low pleural/pericardial glucose can mimic RA)
• Malignant pericardial effusion
• Hypothyroid pericardial effusion
• Uremic pericarditis
• Dressler syndrome (post-MI)

• Primary atherosclerosis (shared risk factors)
• Coronary vasculitis (PAN, Kawasaki disease)
• Other inflammatory arthropathies (AS, psoriatic arthritis - also have elevated CV risk)

• Rheumatic heart disease (mitral > aortic)
• Libman-Sacks endocarditis (SLE)
• Infective endocarditis

• Cardiac sarcoidosis
• Systemic sclerosis
• Cardiac amyloidosis
• SLE

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PULMONARY INVOLVEMENT

Intrathoracic Manifestations of RA

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1. Pleural Effusion

• Exudate; very low glucose (<30 mg/dL) - this is virtually pathognomonic of RA or empyema
• Elevated LDH, elevated RF, low complement
• Variably serous, purulent, milky, or hemorrhagic appearance
• May progress to pseudochylothorax (cholesterol effusion) in chronic disease
• Trapped lung / fibrothorax can result from untreated chronic effusion

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2. Interstitial Lung Disease (ILD)

• UIP pattern is the most frequent histopathological type (honeycomb changes, peripheral/lower lobe basal predominance)
• NSIP is second most common (bilateral ground-glass opacities, fine reticulations, traction bronchiectasis)
• More common in men, seropositive patients, smokers, high disease activity
• May precede joint symptoms in up to 3.5% of patients
• Pulmonary function: restrictive pattern + reduced DLCO
• Prognosis better than idiopathic UIP/IPF; responds better to immunosuppression

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3. Necrobiotic (Rheumatoid) Pulmonary Nodules

• Associated with subcutaneous nodules; wax and wane
• Single or multiple, 2mm to several cm, well-circumscribed
• May cavitate; subpleural location can cause pneumothorax
• Show increased FDG uptake on PET - do NOT misinterpret as metastatic disease
• May occur in association with pulmonary fibrosis and pleural changes

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CXR demonstrating bilateral lower zone changes in RA:

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4. Caplan Syndrome

• RA + pneumoconiosis (coal workers' pneumoconiosis or silicosis)
• Discrete nodules predominantly in upper lobes; appear suddenly
• Histologically identical to necrobiotic nodules
• (Harrison's 22E; Fishman's; Goldman-Cecil)

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Classical HRCT Summary for RA Pulmonary Disease

• Pleural effusions are common
• UIP is more frequent than NSIP (opposite to systemic sclerosis)
• Bronchiectasis in up to 30%
• Obliterative bronchiolitis causes extensive air trapping
• Necrobiotic nodules: well-circumscribed, may cavitate, may be subpleural

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DIFFERENTIAL DIAGNOSIS OF RA PULMONARY MANIFESTATIONS

For ILD / Pulmonary Fibrosis:

For Pleural Effusion in RA:

• SLE pleuritis (glucose normal, ANA +ve)
• Tuberculous pleuritis (lymphocytic; low glucose can overlap - always exclude)
• Malignant effusion (cytology)
• Heart failure (transudatate)
• Empyema (glucose <30 also - key overlap with RA; culture mandatory)

For Pulmonary Nodules in RA:

• Primary lung carcinoma (FDG-avid - PET not diagnostic alone)
• Metastatic disease
• Pulmonary carcinoid
• Granulomatous infections (TB, fungal - especially in immunosuppressed RA patients)
• Wegener's/GPA nodules (cavitating; c-ANCA, PR3)
• Sarcoid nodules

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Key Clinical Pearls

1. Pleuro-pulmonary disease may precede arthritis in a significant minority of RA patients - maintain suspicion even without established RA diagnosis.
2. Glucose <30 mg/dL in pleural fluid = RA or empyema only - always culture to exclude infection.
3. RA-ILD has a better prognosis than IPF and responds better to immunosuppression, but the HRCT UIP pattern is radiologically identical - clinical context (RF, ACPA, joint disease) is essential.
4. Cardiovascular disease is the leading cause of death in RA - the 2x excess risk of IHD and heart failure cannot be explained by traditional risk factors alone.
5. MTX-related lung toxicity can mimic RA-ILD - temporal drug relationship and eosinophilia are clues.
6. FDG-PET: necrobiotic nodules are FDG-avid and must not be mistaken for malignancy.
7. In immunosuppressed RA patients, opportunistic infections (PCP, CMV, aspergillus) must always enter the DD for acute pulmonary deterioration.

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