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Objective.Raynaud’s phenomenon (RP) is an important clinical feature of systemic sclerosis (SSc) for which consistently effective therapies are lacking. The study was designed to assess the safety, tolerability, and efficacy of tadalafil, a selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in this clinical syndrome.Methods.We performed a prospective, randomized, double-blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP secondary to SSc.Results.Thirty-nine subjects completed the study and were evaluable. There were no statistically significant differences in Raynaud Condition Score (RCS), frequency of RP episodes, or duration of RP episodes between treatment groups. Placebo response was a confounding factor. Tadalafil was well tolerated.Conclusion.Tadalafil appears to be safe and well tolerated but lacks efficacy in comparison to placebo as a treatment for RP secondary to SSc.

The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease.To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness.Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment.Lavage was performed in 201 individuals, including 141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P = 0.04), more severe lung function, including a worse forced vital capacity (P = 0.003), worse total lung capacity (P = 0.005) and diffusing capacity of the lung for carbon monoxide (P = 0.004), more extensive ground-glass opacity (P = 0.005), and more extensive fibrosis in the right middle lobe (P = 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P = not significant).The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).

Pulmonary hypertension (PH) is an ominous complication in patients with scleroderma (systemic sclerosis, SSc). We compared noninvasive assessment of PH with pulmonary artery (PA) pressures obtained by right-heart catheterization (RHC).Forty-nine patients with SSc were evaluated for suspected PH based on clinical findings, progressive dyspnea, and pulmonary function tests (PFT). PH was defined as mean PA pressureor = 25 mm Hg, oror = 30 mm Hg after exercise, with normal pulmonary capillary wedge pressure (PCW). Doppler echocardiography (echo) and cardiac magnetic resonance imaging (MRI) were performed within 4 hours of RHC, and the predictive accuracy of the tests was compared.RHC identified 24/49 (49%) patients with PH. The noninvasive cutpoints were: estimated right ventricular systolic pressure47 mm Hg by echo; diameter of the main PA28 mm by MRI; and the ratio of forced vital capacity to diffusion capacity (%FVC/%DLCO)2.0 by PFT. Echo classified 38 subjects correctly (14/24 with and 24/25 without PH; sensitivity 58%, specificity 96%). The area under receiver-operating characteristic curve (AUC) was 0.84 for echo. MRI measurement of PA diameter had a sensitivity of 68% and specificity 71% (AUC 0.78). PFT evaluation had a sensitivity of 71% and specificity of 72% (AUC 0.76).In evaluation of SSc with suspected PH, echo appeared to be the most useful among the noninvasive tests, mainly due to the high specificity, high positive predictive value, and highest AUC. However, due to the low sensitivity of noninvasive testing, RHC should remain the gold standard.

To assess the efficacy and tolerability of bosentan in pulmonary arterial hypertension secondary to systemic sclerosis (SSc-PAH) including patients with restrictive lung disease.We retrospectively reviewed 23 SSc-PAH patients with PAH at baseline [PA systolic pressure (PASP)or= 45 mm Hg by echocardiogram or mean PA pressure25 mm Hg at rest by cardiac catheterization], World Health Organization (WHO) functional classes II-IV, and with data available for 18 months. Bosentan dose was 62.5 mg twice daily for 1 month then 125 mg twice daily. Outcomes were WHO functional class, PASP, and pulmonary function tests (PFT) at 3-month intervals for 18 months.WHO class at baseline 3.1 +/- 0.1 (mean +/- SE); 3 months, 2.5 +/- 0.2*; 6 months, 2.4 +/- 0.2*; 9 months, 2.5 +/- 0.2* (*p0.02 vs baseline, n = 21 to 23), indicating clinical improvement at 9 months. After 9 months, results were not significant versus baseline. Reduction in WHO class by at least one rank was 57% at 3 months; none worsened. After 9 months, WHO class tended to worsen compared to baseline. Baseline PASP was 54 +/- 2 mm Hg (n = 23) and did not change significantly with therapy. Restriction (total lung capacity 76% +/- 4% of predicted) and reduced diffusing capacity (39% +/- 3% of predicted) were unchanged during therapy. Abnormal transaminases in 2 patients (9%) necessitated discontinuing drug in both.Bosentan is clinically beneficial in patients with SSc-PAH including patients with restrictive lung disease, but pulmonary hemodynamics and PFT results remained stable during treatment.