Although the development of pulmonary arterial hypertension (PAH) in mixed connective tissue disease (MCTD) is now recognised as the most important life threatening factor, an effective treatment for PAH has not been established. The response to steroid treatment of PAH related to MCTD varies. Furthermore, Raynaud’s phenomenon is the most common symptom of MCTD and one symptom of the 1996 revised criteria for MCTD in Japan.¹ However, a reliable and consistently effective treatment for Raynaud’s phenomenon in MCTD has not been established.

Sildenafil is reportedly effective for PAH and Raynaud’s phenomenon in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE).^2–,⁴ However, the effect of sildenafil on PAH and Raynaud’s phenomenon in MCTD has not been reported.

CASE REPORT

We describe a case of PAH and Raynaud’s phenomenon in a 39 year old female patient with MCTD, in which we evaluated the effects of steroids and sildenafil.

The patient had had dyspnoea on exertion and Raynaud’s phenomenon since December 2002. Because of the worsening of dyspnoea on exertion, she was admitted to our hospital in November 2003. She was diagnosed as having MCTD based on the 1996 revised criteria for MCTD in Japan.¹ Her symptoms and exercise capacity as defined by the New York Heart Association (NYHA) was functional class III. An echocardiogram showed right atrial and ventricular dilatation and the estimated pulmonary artery systolic pressure was 53.6 mm Hg (resulting from tricuspid regurgitation identified on Doppler ultrasonography). Pulmonary function tests showed a diffusing capacity to alveolar volume ratio (Tlco/VA) of 78.0%. She was diagnosed with PAH from these findings.

Methylprednisone pulse therapy (1 g/day for 3 consecutive days) followed by prednisone (50 mg/day) was started. She underwent right heart catheterisation before and 4 weeks after the start of steroid treatment. Mean pulmonary artery pressure declined from 39 mm Hg to 28 mm Hg. The 6 minute walking distance increased from 100 m to 410 m and NYHA functional class improved from III to I. Furthermore, Tlco/VA increased from 78.0% to 87.9%. Serum IgG antiendothelial cell antibody (AECA) titres measured as described before⁵ decreased from 45.0 U/ml to 6.0 U/ml (normal upper limit 7.14 U/ml).

Before the start of steroid treatment, the mean pulmonary artery pressure and pulmonary vascular resistance (PVR) measured by right heart catheterisation before and 40 minutes after the oral administration of sildenafil (50 mg) were reduced by 10.3% and 28.9%, respectively. Four weeks after the start of steroid treatment, the mean finger skin surface temperature of both hands by thermography before and 60 minutes after the oral administration of sildenafil (50 mg) showed an increase of 6.4°C (fig 1⇓).

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Figure 1

 The finger skin surface temperature of both hands measured using an infrared thermal imaging camera, before (A) and 60 minutes after (B) the oral administration of sildenafil (50 mg) in a temperature controlled room (25±1°C), is shown by colour imaging.

DISCUSSION

Serum IgG AECA in this patient showed a high titre before the start of steroid treatment. Serum IgG AECA may reportedly be related to the appearance, development, and activity of PAH in SLE⁵ and MCTD.⁶ General case reports of the improvement of PAH during steroid or immunosuppressive treatment have been published.^7,8 Based on these observations, PAH in this patient might be still in the early and active stage, which responded to steroid treatment. Early detection of PAH should allow an earlier and more aggressive therapeutic approach such as steroid pulse therapy in these patients, before irreversible vascular lesions occur.

Sildenafil increases intracellular cyclic guanosine monophosphate levels in vascular smooth muscle cells, thereby mediating vasorelaxation within 1 hour. In this patient a positive response—decrease of mean pulmonary artery pressure and PVR and increase of peripheral blood flow—was achieved by only a single oral administration of sildenafil. Sildenafil has been reported to be a selective pulmonary vasodilator⁹ but may also work as a vasodilator of peripheral arteries. These observations suggest that long term use of oral sildenafil may improve exercise tolerance and quality of life in MCTD patients with PAH and Raynaud’s phenomenon.