Unmasking Connective Tissue Disease Through Pulmonary Hypertension: A Diagnostic Challenge

Abstract

Pulmonary arterial hypertension (PAH) is a severe and potentially life-threatening manifestation of connective tissue diseases, often presenting insidiously and complicating timely diagnosis. We report the case of a 48-year-old Saudi woman with no prior chronic illness who presented with progressive exertional dyspnea and fatigue over six weeks. Examination revealed mild central cyanosis, elevated jugular venous pressure, and a prominent right ventricular heave. Laboratory evaluation showed elevated NT-proBNP and mild hypoxemia, while echocardiography demonstrated right ventricular dilation and an estimated pulmonary artery systolic pressure of 70 mmHg. Right heart catheterization confirmed pre-capillary pulmonary hypertension. Serologic workup revealed high-titer anti-U1 RNP antibodies, ANA positivity, and features consistent with mixed connective tissue disease (MCTD), with no evidence of left heart disease, thromboembolic disease, or significant interstitial lung involvement. Management included combination PAH-targeted therapy with an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor, alongside low-dose corticosteroid immunosuppression. Supportive care comprised oxygen supplementation and close hemodynamic monitoring. Over three months, the patient’s functional status improved from WHO functional class III to II, with reduction in NT-proBNP and increased six-minute walk distance. This case underscores the diagnostic challenge of MCTD presenting primarily with PAH, emphasizing that subtle systemic features may precede cardiovascular compromise. Early recognition, prompt hemodynamic assessment, and a multidisciplinary management strategy are crucial to improve prognosis and prevent irreversible right ventricular dysfunction. Clinicians should maintain a high index of suspicion for PAH in patients with connective tissue disease, even in the absence of overt systemic manifestations.