A 52-year-old woman comes to the emergency department due to worsening chest pain and shortness of breath for the past week. The patient has right-sided, "stabbing" pain whenever she takes a deep breath associated with shortness of breath on moderate exertion. She has no fever, chills, or leg swelling but has had frequent pain in her hands and feet. The patient has pain while walking in the morning and is unable to bend her fingers to hold a coffee cup. She takes no medications. For several years in her twenties, the patient used tobacco (half-pack of cigarettes daily). She does not drink alcohol. Temperature is 37.2 (99 F), blood pressure is 142/80 mm Hg, pulse is 84/min, and respirations are 18/min. BMI is 30 kg/m2. Lung auscultation reveals bilateral fine inspiratory crackles and decreased breath sounds over the right base. Heart sounds are normal with no murmurs. The patient has no rashes. The wrists and small joints of the hands are mildly swollen and tender bilaterally; there is no clubbing. Laboratory results are as follows:
| Hematocrit | 32% |
| Leukocytes | 8,200/mm3 |
| Serum creatinine | 0.8 mg/dL |
| Serum protein | 6 g/dL |
| Lactate dehydrogenase | 70 U/L |
| TSH | 4.0 µU/mL |
| Antinuclear antibody (ANA) | negative |
Chest x-ray shows increased interstitial markings and a moderate-sized right pleural effusion. Diagnostic thoracentesis reveals pleural fluid protein of 4 g/dL, lactate dehydrogenase of 950 U/L, and glucose of 10 mg/dL. Which of the following is the most likely underlying cause of this patient's pleural effusion?
Exudative & transudative pleural effusions | ||
Exudate | Transudate | |
Light criteria | Pleural protein/serum protein >0.5 OR Pleural LDH/serum LDH >0.6 OR Pleural LDH >2/3 upper limit of normal of serum LDH | Exudate criteria not met |
Pathophysiology | Inflammatory disruption of vascular permeability | Change in hydrostatic or oncotic pressure |
Common causes |
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CABG = coronary artery bypass grafting; LDH = lactate dehydrogenase; RA = rheumatoid arthritis; SLE = systemic lupus erythematosus; TB = tuberculosis. | ||
This patient with pleuritic chest pain has a pleural effusion with a high pleural fluid/serum protein ratio of 0.67 (4 g/dL / 6 g/dL) and a high lactate dehydrogenase (LDH) ratio of 13.6 (950 U/L / 70 U/L). Based on the Light criteria these findings are consistent with an exudative effusion, which usually results from an inflammatory disruption of vascular permeability. Several features of this patient's presentation suggest rheumatoid arthritis (RA) as the underlying diagnosis:
Rheumatoid effusions are often marked by very low (eg, <50 mg/dL) glucose and very high LDH (>700 U/L); they may also have a low pH resembling bacterial empyema. In general, effusions with very low glucose levels are most often due to RA, empyema, malignancy, or tuberculosis.
The patient has evidence of an inflammatory arthritis with joint swelling, tenderness, and morning stiffness.
Her fine crackles on examination and increased interstitial markings on x-ray are consistent with interstitial lung disease (ILD), which, along with pulmonary nodules, is a pulmonary manifestation of RA.
Exudative pleural effusions are a relatively common extraarticular manifestation of RA, although they may be asymptomatic and usually resolve spontaneously.
(Choice A) Pleural effusions in decompensated heart failure are typically transudative (ie, due to increased pulmonary capillary hydrostatic pressure), with lower protein and LDH levels than in this patient.
(Choices B and D) Diffuse cutaneous systemic sclerosis (scleroderma) can cause finger contractures (eg, difficulty bending the fingers) and is associated with ILD; however, pleural effusion is uncommon, patients often have Raynaud syndrome, and inflammatory arthritis is rare. Sarcoidosis also causes ILD and arthritis; however, pleural effusions are uncommon, and arthritis typically involves the ankles and is often seen in association with hilar adenopathy and erythema nodosum (ie, Lofgren syndrome).
(Choice E) Systemic lupus erythematosus (SLE) can cause ILD and pleural effusions and can also cause inflammatory arthritis resembling RA. However, antinuclear antibodies (ANA) are extremely (>95%) sensitive for SLE, with a positive result seen in 98%-100% of patients with active SLE; therefore, this patient's negative ANA result makes SLE much less likely. In contrast, RA is associated with a positive ANA result in <50% of cases; therefore, the negative ANA result in this patient does not rule out the diagnosis, especially given the other findings (eg, exudative effusion with low glucose, inflammatory arthritis with morning stiffness).
Educational objective:
Rheumatoid arthritis can cause exudative pleural effusions characterized by low glucose, very high lactate dehydrogenase, and (often) low pH and is associated with interstitial lung disease.