A pleural effusion (PE) is accumulation of excessive fluid in the pleural space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.01 mL/kg weight per hour, and is cleared by lymphatic absorption leaving behind only 5–15 mL of fluid, which helps maintaining a functional vacuum between the parietal and visceral pleurae. Excess fluid within the pleural space can impair inspiration by upsetting the functional vacuum and hydrostatically increasing the resistance against lung expansion, resulting in a fully or partially collapsed lung [1]. Various types of fluid can accumulate in the pleural space, viz., serous (hydrothorax), blood (hemothorax), pus (pyothorax or empyema), chyle (chylothorax), and urine (urinothorax). Excessive PE results from two pathophysiological derangements; (a) transudates due to excessive production, reduced resorption and decrease oncotic pressure as in congestive heart failure, renal failure, liver cirrhosis, nephrotic syndrome, and Meig’s syndrome while (b) exudative ones result from pleural damage by trauma, infection, malignancy, and autoimmune diseases [2]. In the United States, the incidence of PE is estimated to be at least 1.5 million cases annually and the industrialized countries the prevalence of is 320 cases per 100,000 people [3]. Most of these cases are caused by congestive heart failure, bacterial pneumonia, malignancy, and pulmonary embolism. In our case report, we present a patient with progressive and unilateral PE due to rheumatoid arthritis (RA) yet without systemic manifestations of disease which is exceedingly rare.

A 70-year-old man presented with shortness of breath for two weeks. He denied fever, chest and abdominal pain, skin rash, and joint pains. Past history was significant for type II diabetes mellitus (DM) for 10 years that had disappeared after progressive worsening of his renal function with edema and hypertension in the past three years. Lately, he was started on hemodialysis and kidney biopsy had confirmed that he had advanced nodular glomerulosclerosis. On his initial physical examination, the patient was conscious, oriented X3, and in distress of shortness of breath. Blood pressure was 120/80 mmHg. He was afebrile with a body weight of 77 kg. He did not have lymphadenopathy, goiter, jugular venous distension, or edema. Systemic examination did not show abnormality except for dull percussion at right lower chest zones. Laboratory investigations showed normal peripheral leukocytic and platelets counts. Hemoglobin was 110 g/L with normal mean corpuscular volume (MCV). Serum urea and creatinine were elevated at 21 mmol/L and 440 umol/L, respectively. Serum glucose was 12 mmol/L. Serum electrolytes and liver functions were normal except for albumin at 28 g/L. Serum lactate dehydrogenase (LDH) was 280 U/L. Serum cholesterol was 6 mmol/L. Thyroid stimulating hormone (TSH) was normal. Urine routine and microscopy showed 3(+) protein without hematuria and pyuria. Serum complements (C3 and C4) and protein electrophoresis were normal. Antinuclear antibody (ANA), anti-ds DNA, antineutrophil cytoplasmic antibody (ANCA), anti-GBM AB, hepatitis B surface antigen, and anti-HCV antibodies were negative. Chest X-ray showed large right-sided pleural effusion without pulmonary infiltrate and lymphadenopathy (Figure 1A). Electrocardiogram (ECG) was normal. Abdominal and pelvic ultrasound was normal except for bilateral normal-sized yet echogenic kidneys and without ascites. Ultrasound examination of the chest confirmed the effusion and allowed its pleural tapping (Figure 2). Its analysis showed pH: 7.4, leukocytic count: 600 cells/mm3 of which 82% were lymphocytes, LDH 1528 U/L, glucose 6 mmol/L. Pleural fluid and blood cultures for bacteria, fungus, and mycobacteria were negative. Smear of pleural fluid, stained with Giemsa stain, showed spindle and giant multinucleated macrophage (Figure 3). No acid-fast bacilli were seen on Ziehl-Neelsen stain. Real-time polymerase chain reaction (PCR) for mycobacteria tuberculosis was negative. Based on such data which suggested RA, anti-cyclic citrullinated peptide antibody was done. The results were very high (280 EU/mL. Normal < 20) which further confirmed the diagnosis of PE associated with RA. Moreover, kidney biopsy was done and showed diffuse nodular glomerulosclerosis without granulomatous interstitial nephritis. Ancillary stains were negative for Congo-red and immune deposits. After establishment of final diagnosis; the patient was treated with Prednisone 60 mg daily and the effusion has decreased dramatically one month later (Figure 1B). To avoid long-term steroid side effects on his DM and bones; he was treated also with Rituximab 1 g followed by 1 g two weeks later and Prednisone was tapered down and discontinued after two months. Up to one year of follow-up; the patient did not manifest active RA or recurrence of his PE.

Rheumatoid arthritis (RA) is an autoimmune disease that manifests as a progressive mutilating arthritis with a worldwide prevalence at 0.24% [4]. Its extra-articular manifestations are rare [5]. Pleuropulmonary manifestations of RA without primary articular symptoms are exceedingly rare and therefore pose difficult problems in differential diagnosis [6]. In our elderly and diabetic patient with severe renal disease the list of differential diagnosis is huge yet the algorithm plan had narrowed the diagnosis. The initial step was the pleural tap which, based on criteria, has confirmed its exudative nature and ruled out fluid overload or hypoalbuminemia associated with his diabetic renal disease [7]. Lack of significant pyothorax and culture ruled out parapnemonic etiology. Moreover, lack of lung infiltrates, lymphadenopathy, and negative PE polymerase chain reaction (PCR) test for mycobacteria excluded tuberculosis [8]. Moreover, his kidney biopsy showed diabetic glomerulosclerosis without evidence of interstitial granulomatous tuberculous involvement. Autoimmune workup had ruled out systemic diseases such as systemic lupus erythematosis and vasculitis. Patients with severe renal disease can develop uremic pleuropericarditis and subsequent effusions yet the modest level of his renal disease was against such complication. In our patient, the low PE glucose compared to plasma and its cytopathological findings were suggestive of RA [9]. Finally, the high level of anti-CCP consolidated the diagnosis. The latter test has a sensitivity of 61.6–75.2% for rheumatoid arthritis and specificity of 94–99% [10]. In difficult cases; thoracoscopic pleural biopsy may assist in diagnosis and exclusion of other etiologies [11].

Rheumatoid arthritis should be considered in patients presenting with exudative PE that lacks history of trauma, and manifestations of infection, malignancy, and autoimmune diseases. High anti-CCP and cytological examination are useful in diagnosis.