A 50-year-old woman was admitted due to high fever and progressive dyspnea for 20 days. For ten years, she suffered from arthritis which was treated irregularly, without specific evaluation, at a private clinic. Eleven days before, she visited another hospital because of fever, cough, sputum and dyspnea with mild pleuritic chest pain. She was managed under the impression of tuberculous pleurisy, but she did not improve with anti-tuberculous medication. A chest radiography showed right pleural effusion with bilateral pulmonary infiltrations (Figure 1A). Cytology of pleural fluid revealed mesothelial cells, histiocytes and neutrophils. Serum creatinine level was 2.2 mg/dL. She was brought to this hospital for further evaluation and management.
On admission, she complained of fever, cough and dyspnea. Her body weight was 33 kg and her vital signs were as follows: temperature 38.6 C; heart rate 120/min; and respiratory rate 28/min. At that time, she also had keratoconjunctivitis sicca and xerostomia. On physical examination, she had bibasilar crackling rales. Pale conjunctiva, hepatomegaly by two fingers width below the costal margin and pretibial pitting edema were also discovered. But, clubbing of finger and cyanosis were absent.
A chest radiograph showed pneumonic infiltrations in both lower lung fields with pleural effusion (Figure 1B). Laboratory studies revealed hemoglobin of 8.5 g/dL, hematocrit of 24%, white blood cell count of 3900/mm3 (13% of band form, 85% of segment form), platelet count of 148,000/mm3 and ESR of 72 mm/hr. Serum creatinine was 2.5 mg/dL, protein was 7.2 g/dL and albumin was 2.5 g/dL. Urinalysis showed proteinuria (+2) and hematuria (+4). Antinuclear antibody was positive (1/640, speckled pattern), but anti-DNA antibody was negative. Tests for anti-Ro, anti-La and anti-RNP antibodies were positive. The level of C3 and C4 were decreased to 25 mg/dL (normal 45-100 mg/dL) and 9 mg/dL (normal 10-40 mg/dL), respectively. C-reactive protein was 7.2 mg/dL (normal <0.5) and rheumatoid factor was 52 IU/mL (normal <20). Direct Coombs' test was positive, but indirect Coombs' test was negative.
Peripheral blood smear demonstrated normochromic normocytic anemia with mild leukopenia and thrombocytopenia. Blood culture grew nothing. Ziehl-Neelson stains for acid-fast bacilli of her sputum were negative and cultures for M. tuberculosis were negative 3 consecutive times. On 24-hour urine collection, protein was 3.0 g/dL and creatinine clearance was decreased to 20 mL/min. Determination of urinary Bence-Jones protein revealed no abnormality. Immunoelectrophoresis of serum proteins revealed polyclonal increase at gamma-region, especially IgG lane. A pleural fluid study disclosed that straw-colored fluid contained 127 leukocytes/muL (neutrophil 26%, lymphocyte 74%), protein 1.7 g/dL, lactic dehydrogenase 972 mg/dL and glucose 37 mg/dL and had a high likelihood of being an exudate. AFB smear and culture of pleural fluid did not show any organism. Test for IgM antibody to Epstein-Barr (E-B) virus was positive in the serum. Antineutrophil cytoplasmic antibodies (ANCA), Human Immunodeficient Virus (HIV) and Cytomegalovirus (CMV) assays were all negative.
Pulmonary function test showed normal ventilatory pattern with reduced diffusion capacity: forced vital capacity (FVC) 1.90 L (84% of predictive value), forced expiratory volume in one second (FEV1) 1.63 L (94% of predictive value), FEV1/FVC 113%, total lung capacities (TLC) 2.78 L (88% of predictive value) and diffusing capacity of the lung DLCO) 6.5 mL/min/mmHg (54% of predictive value). Echocardiography revealed left ventricular dysfunction with moderate amount of pericardial effusion.
Sialography of salivary gland showed multiple-sized ectatic changes in acina without dilatation and filling defect in the main duct (Figure 2). On biopsy finding of the lower lip, hyperkeratosis and spongiosis were seen, and lymphocytes infiltrated the dermis with exocytosis to the epidermis which was compatible with Sjogren's syndrome (Figure 3).
High-resolution computed tomography of the chest demonstrated bilateral consolidations in both lower lung zones, associated with bilateral pleural effusion and moderate amount of pericardial effusion (Figure 4).
An open lung biopsy was performed at the right lower lobe of the lung. There was dense lymphoplasmacytic infiltration in the interstitium of the lung parenchyme (Figure 5A) and the pleura forming reactive lymphoid follicles with germinal centers (Figure 5B). Multifocal areas of vasculitis (Figure 5C) and interstitial fibrosis were shown without any fibroblastic plug or honeycombing cystic change. The immunohistochemical stains failed to reveal monoclonality of these lymphocytic infiltrations as below; LCA (CD45RB) (+), CD3 (+) and L26 (CD20) (+). In situ hybridization of paraffin block tissue with anti-Ebstein-Barr virus antibody (NCL-EBV-K, Novocastra Lab, UK) was positive.
The patient was treated with prednisolone of 1 mg/kg/day for one month. But, she had no improvement on radiologic finding and showed generalized edema as an adverse effect of steroids. With prednisolone tapering, she was also added oral cyclophosphamide 50 mg/day. Following this therapy, her condition significantly improved in subjective symptoms, physical signs and objective pulmonary function and radiologic findings (Figure 1C).
The inflammatory laboratory markers were still slightly increased, but pulmonary function test and chest radiograph were nearly normalized.
CT scan of the chest shows bilateral consolidation in both lower lung zones. Bilateral pleural effusion and pericardial effusion are present.