Diagnosis of Pulmonary Arterial Hypertension in a Patient With Systemic Sclerosis

Jörg HW Distler, MD; Marius M Hoeper, MD; Oliver Distler, MD


Nat Clin Pract Rheumatol. 2008;4(3):160-164. 

In This Article

Summary and the Case

Background: A 42-year-old woman with limited cutaneous systemic sclerosis presented with rapid-onset dyspnea on exertion, which had developed over the previous 8 weeks. She had not experienced any dyspnea before this period. Transthoracic Doppler echocardiography performed 6 months before presentation demonstrated an estimated right ventricular systolic pressure of 32 mmHg. Lung function tests also performed at that time revealed a decreased diffusion capacity for carbon monoxide of 54% and normal lung volumes, and high-resolution CT scan of the lungs was normal.
Investigations: Physical investigation, CBC, analysis of C-reactive protein and pro-brain natriuretic peptide, transthoracic Doppler echocardiography, six-minute walk test, lung function tests including diffusion capacity for carbon monoxide, right heart catheter, high-resolution CT scan, and ventilation/perfusion scan.
Diagnosis: Pulmonary arterial hypertension associated with limited cutaneous systemic sclerosis.
Management: Treatment with oral anticoagulation therapy and the endothelin-receptor antagonist bosentan. Monitoring of adverse effects of bosentan therapy was performed using liver function tests.

A 42-year-old woman was diagnosed with limited cutaneous systemic sclerosis (SSc) three years ago. At the time of diagnosis, she had suffered from Raynaud's phenomenon for six years and recurrent finger-tip ulcers during the last two winter seasons. The patient reported having no other problems, including no dyspnea on exertion. Physical examination demonstrated two small inactive ulcers at the tips of the third and fourth fingers of the left hand, acrosclerosis with a total modified Rodnan skin score of nine, and telangiectasias on the face. Physical examination did not reveal any other pathological findings. Nailfold capillaroscopy demonstrated a reduced capillary density with dilated and giant capillaries, two microhemorrhages and a few avascular areas highly suggestive of SSc. Lung function tests revealed normal lung volumes and a predicted diffusing capacity for carbon monoxide (DLCO) of 54%. High-resolution CT (HRCT) scanning of the lungs did not demonstrate pathologic findings. The right ventricular systolic pressure (RVSP), as estimated by transthoracic Doppler echocardiography (TTE) was 32 mmHg. Laboratory tests showed an antinuclear antibody titer of 1:10000 and presence of anticentromere antibodies, but not anti-topoisomerase I antibodies or other extractable nuclear antigens. Serum level of N-terminal pro-B-type natriuretic peptide (pro-BNP), which was measured at baseline for comparison at later follow-ups, was within normal limits. The patient was prescribed nifedipine and paraffin baths, and advised to avoid exposure to cold.

The patient responded well to this symptomatic treatment. The intensity and frequency of her Raynaud's attacks decreased considerably and she did not develop digital ulcers during the following years. At the first two annual follow-ups no evidence of progression of SSc was observed. The patient's modified Rodnan skin score remained unchanged, lung function tests demonstrated normal lung volumes, and her DLCO was stable. The TTE-estimated RVSPs were 28–33 mmHg, and chest X-rays were normal.

At the third, and most recent, annual follow-up the patient reported experiencing shortness of breath when climbing stairs. She first noted these symptoms eight weeks before the follow-up appointment and dyspnea had progressed since then. She was otherwise well and had noticed no other physical changes. On physical examination, a slightly accentuated pulmonary component of the second heart sound was noticed, but no murmurs were audible. Lung sounds were normal. No peripheral edema, ascites, hepatomegaly, or jugular vein distension were detectable. The patient's body temperature and CBC were within normal ranges, and her C-reactive protein level was not elevated. TTE was performed and revealed an estimated RVSP of 41 mmHg without evidence of left heart disease. Lung function tests demonstrated a further decrease of the DLCO from 54% to 43%, whereas lung volumes remained normal. In addition, pro-BNP level was found to be elevated to threefold higher than normal values. Right heart catheterization was used to confirm the suspected diagnosis of pulmonary arterial hypertension (PAH). The resting mean pulmonary arterial pressure in this patient was 36 mmHg, with a normal pulmonary wedge pressure of 8 mmHg, an increased pulmonary vascular resistance of 509 dynes/sec/cm5, and a cardiac index of 2.2 l/min/m2. After confirming the diagnosis of PAH by using right heart catheterization, interstitial lung disease and thromboembolic disease were excluded by HRCT and ventilation/perfusion scans. The patient was, therefore, classified as having PAH associated with limited cutaneous SSc. A six-minute walk test was performed with a result of 460 meters and a Borg dyspnea index of 3.

The patient's dyspnea progressed rapidly, with symptoms occurring after slight to moderate exercise, and her PAH was classified as New York Heart Association (NYHA) functional class III. Therapy with oral anticoagulation (phenprocoumon, prothrombin time target international normalized ratio 2.0–3.0) and the oral endothelin A and B receptor antagonist bosentan (62.5 mg twice daily for four weeks, followed by a maintenance dose of 125 mg twice daily) was initiated for the treatment of PAH. The patient responded well to the treatment, with an improvement to NYHA class II after four weeks and an increase in the six-minute walking distance from 460 to 520 meters. In addition, pro-BNP levels dropped to within 1.5 fold of the upper normal range. Bosentan therapy was well tolerated and liver function tests remained normal.


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