Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue diseases (CTDs) including systemic sclerosis and systemic lupus erythematosus (SLE). The prevalence of PAH in SLE is estimated to be 0.5% to 17.5%. The pathophysiology of PAH involves multiple mechanisms from vasculitis and in-situ thrombosis to interstitial pulmonary fibrosis which increases pulmonary vascular resistance, potentially leading to right heart failure. Immune and inflammatory mechanisms may play a significant role in the pathogenesis or progression of PAH in patients with CTDs, establishing a role for anti-inflammatory and immunosuppressive therapies. The leading predictors of PAH in SLE are Raynaud phenomenon, anti-U1RNP antibody, and anticardiolipin antibody positivity. The first-line of diagnostic testing for patients with suspected SLE-associated PAH (SLE-aPAH) involves obtaining a Doppler echocardiogram. Once the diagnosis is confirmed by right heart catheterization, SLE-aPAH patients are generally treated with oxygen, anticoagulants, and vasodilators. Although the prognosis and therapeutic responsiveness of these patients have improved with the addition of intensive immunosuppressive therapies, these treatments are still largely unproven. Recent data showed  one-year survival rate for SLE-aPAH patients at 94%. Pulmonary arterial hypertension (PAH) is a complex and devastating disease. PAH is defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, pulmonary artery wedge pressure (PAWP), or left ventricular end diastolic pressure ≤15 mmHg and increased pulmonary vascular resistance (PVR). PAH can be idiopathic (IPAH), heritable, drug, or toxin induced or associated with human immunodeficiency virus infection, portal hypertension, congenital heart diseases, schistosomiasis, or chronic hemolytic anemia. It can also be associated with varied connective tissue diseases (CTDs) such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or mixed connective tissue disease (MCTD). PAH disease progression is characterized by narrowing of the pulmonary arterial bed due to extensive endothelial, adventitial and smooth muscle dysfunction. Genetic, environmental, and other predisposing conditions, including vasodilator and vasoconstrictor imbalance, inflammatory and uncontrolled immune response, and an imbalance between proliferation and apoptosis, lead to constrained blood flow, potentially resulting in increased pulmonary vascular resistance.

Although PAH is documented in SLE, is not very common. Pathophysiologic mechanisms are same as for Idiopathic PAH. Treatments are also same, the only drug shown to be effective to reduce pulmonary artery pressure is CCB with other supportive measures like Diuretics and Sildenafil. I have one patient with SLE with ILD with sev PAH, she is responding to Nifedepine, Sildenafil and low dose Diuretic.

Although direct injury mediated by immunologic factors has not been clearly  demonstrated , the presence of antinuclear antibodies , anti DNA antibodies , immunoglobulins and complement fractions on the pulmonary vessels in PAH- SLE related patiens, sugessted an immune basis. Cyclophosphamide and in refractory cases Rituximab could be added to the standard treatment.

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Nothig to add about pathogenesis. We had some patients on cyclophosphamide or/and corticosteroids. Attempts to withdraw these therapy resulted in patients' condition worsening.

Thank you Ravi Kant, Bhupen, Javier, and Yuriy for all of your responses.  The literature is sparse as to the treatment of Pulmonary Arterial Hypertension.  You all have included literature examples and anecdotal evidence which is always a good combination.  The etiology seems to be important in determining the treatment in the context of pulmonary hypertension.

I agree with the comments above. In the US, most of these patients are eventually referred to pulmonary hypertension centers of excellence, and following a right heart cath, their treatment revolves around the use of sildenafil, CCB, anticoagulants, prostacyclin, bosentan, etc, in various combinations, as above-aluded to. Usually, these patients are already on some type of immunosuppressive therapy, including Plaquenil, however their use is not necessarily directed at or dictated by the PH bur rather at the underlying inflammatory disease,