Severe Pulmonary Hypertension in Primary Sjögren's Syndrome
A 65-year-old female was presented with dyspnea on exertion (New York Heart Association, NYHA class III) for over a period of 1 year. For 5 years, she had complained of dry mouth, intermittent dry eye, and gritty feeling under the eyelids. However, she did not have Raynaud's phenomenon or parotid swelling. She denied taking anorexiants or other drugs. Further, she did not have any sort of family history.\nBlood pressure, pulse rate, and respiration rate were 114/78 mm Hg, 92 per minute, and 24 per minute, respectively. Cardiovascular examination revealed a grade 2/6 systolic murmur in the left low parasternal area, a more accentuated P2 than A2, and both jugular veins that are both slightly distended.\nLaboratory exam disclosed polyclonal hypergammaglobulinemia identified by slightly increased total protein (8.2 g/dL, normal 6.5-8.1 g/dL) and gamma globulin (22.4%, normal 11.1-18.8%). Autoantibody tests showed positive results for anti-nuclear antibodies (1 : 640, speckled, anticytoplasmic antibody: positive), rheumatoid factors (57.10 IU/mL, normal <14 IU/mL), and anti-Ro (SSA) antibodies (3+), while anti-neutrophil cytoplasmic antibodies (ANCA), antibodies to La (SSB), double stranded DNA, Sm, ribonucleoprotein (RNP), topoisomerase-I (Scl-70), histidyl-tRNA synthetase (Jo-1) were negative. Antibodies to cardiolipin and lupus anticoagulant were also negative. Serum complements protein levels were all slightly decreased (C3 87.0 mg/dL, normal 90-180 mg/dL; C4 7.2 mg/dL, normal 10-40 mg/dL; CH50 21.6 U/mL, normal 34-71 U/mL). Anti-human immunodeficiency virus antibodies, hepatitis B virus antigen and antibodies, and anti-hepatitis C antibodies were all negative. Erythrocyte sedimentation rate was increased (42 mm/hour, normal 0-20 mm/hour). Hemoglobin, white blood cell and platelet counts, and urine test were within normal limits. N-terminal pro B-type natriuretic peptide level was 1469.1 pg/mL (normal 0-125 pg/mL). Creatinine kinase-MB and troponin-I were also within normal limits. Arterial blood gas analysis in room air showed pH 7.44, pO2 78 mm Hg, and pCO2 34 mm Hg.\nPulmonary function test revealed normal ventilatory pattern with normal CO diffusion capacity. Chest X-ray demonstrated grossly normal lung fields with a mildly enlarged right ventricle. Electrocar-diogram showed tall, peak P waves in lead II, III, and aVF, suggesting right atrial enlargement. Transthoracic echocardiography showed a mildly enlarged and thick right ventricle, hypokinetic right ventricular free wall, grade II tricuspid regurgitation, and peak tricuspid regurgitation jet velocity of 4.64 m/s with an estimated right ventricular systolic pressure (RVSP) of 91.1 mm Hg (). Transthoracic and transesophageal echocardiography excluded any other congenital, valvular, and myocardial diseases. Right heart catheterization also revealed severe PH. Pulmonary artery pressure was 74/27 mm Hg (mean 46 mm Hg) with a pulmonary capillary wedge pressure of 7 mm Hg (). Cardiac index was calculated as 2.27 L/min/m2 and pulmonary vascular resistance was 11 Wood units. Elevated pulmonary artery pressure was not significantly decreased with adenosine infusion. Chest computed tomography and lung perfusion scan did not show abnormal findings compatible with pulmonary embolism. Schirmer's test was positive. Salivary gland scintigraphy disclosed severely decreased tracer uptakes in both parotid and submandibular glands.\nConsidering her clinical, laboratory, cardiologic, imaging findings and the Revised International Classification Criteria for Sjögren's Syndrome by the American-European Consensus Group, she was clearly diagnosed with severe PH associated with primary Sjögren's syndrome. She was treated with 62.5 mg endothelin receptor antagonist (Bosentan®) twice a day for the initial month and 125 mg twice a day for the following months, 200 mg hydroxychloroquine twice a day, 50 mg azathioprine twice a day, and topical corticosteroid and sodium hyaluronidate eye drops. A follow-up transthoracic echocardiography after 6 months of treatment showed somewhat improved right ventricle contractility and decreased estimated RVSP (65.5 mm Hg) compared to the initial exam (). Equally, her dyspnea symptom was much improved and uneventfully, she is being followed up at an outpatient clinic.