Investigations showed no evidence of neoplasms, nor any bacterial, viral, or fungal infections. Neither the history nor clinical findings suggested collagen disease as the underlying cause of the pleural abnormalities. Test results for LE cells and DNA antibodies in three patients (No. 1, 3, and 4) were negative. In patient 2, antinuclear antibodies (IgM) were weakly positive in a titer of 1:10; in the others, they were negative. Mild eosinophilia of 7 percent was found in patient 1. The initial erythrocyte sedimentation rate (ESR) values were 20, 77, 72, and 70 mm/h, and the respective C-reactive protein values, measured in patients 2, 3, and 4 were 58, 116, and 70 g/L. In patient 4, serum IgG concentration was raised (19.2 g/L). The C4 levels were raised in patients 1 and 4 in whom it was measured.
There was no roentgenographic evidence of cardiac abnormalities. The presence of pleural fluid in patients 2 and 3 was confirmed by repeated ultrasound examinations. Pleural fluid could be obtained from two patients (twice in No. 1, once in No. 4). The repeat aspiration in patient 1 was performed three weeks after discontinuing bromocriptine. It was an exudate in both patients (Table 2) as indicated by high protein values and raised LDH fluid-to-serum-ratio. Glucose fluid-to-serum ratio and lysozyme values were normal in both patients. Cytologic examination showed lymphocytic predominance with no evidence of malignancy. A transbronchial lung biopsy obtained from patient 2 showed interstitial fibrosis consisting of mature collagen, but the alveolar architecture was preserved.
After withdrawal of bromocriptine, subjective improvement occurred gradually in all patients. In patient 1, the pleural fluid disappeared within five months, but a minimal right pleural thickening was seen. In the other three patients, the pleural eflusions disappeared, and roentgenographic abnormalities diminished, but both pulmonary and pleural changes persisted after follow-up. The most marked abnormalities were seen in patient 4, and his x-ray film showed the least resolution. No significant improvements were found in pulmonary function (Table 3), but these measurements were performed in the acute stage in only one patient (No. 2). The ESR and C-reactive protein values gradually decreased in all the patients tested during a follow-up period of at least 11 months.
Table 2—Pleural Fluid Findings in I\vo Patients
|Patient||Date||Leukocytes(10°/L)||Differentiation Count (%)||Protein(g/L)||LDH Fluid-to-Serum Ratio*||DNA Antibodies(<5)||Glucose Fluid-to-Serum Ratio (>0.5)|
|1||Dec 3||2.7||Neutrophils 2||55||1.36||1.5||0.66|
|Jan 22||1.3||Neutrophils 1||49||1.65||2.6||0.91|
|2||Sept 9||0.32||Neutrophils 1||35||1.34||0.5||0.57|
Table 3—Lung Function Tests of the Four Patients Expressed as Percentage of Predicted Values
|Patient||Time, Mo After Cessation of Drug||VC||FEV,||FEV*||TLco||Kco||TLC|