Pulmonary complications are the leading cause of death in scleroderma and an important feature in both systemic lupus erythematosus and patients with overlap syndromes (mixed presentations of scleroderma and lupus). In scleroderma, 10-15% of patients have evidence of pulmonary arterial hypertension and another 10-15% of patients have pulmonary hypertension as a complication of interstitial lung disease and/or left ventricular dysfunction.
Pulmonary hypertension should be suspected if there is reduced exercise capacity-fatigue or shortness of breath on exertion. Patients with scleroderma are limited by their musculoskeletal disease features and become physically deconditioned as an intrinsic feature of their underlying disease. A high clinical index of suspicion for pulmonary hypertension is appropriate for all patients.
In general, the PAH of scleroderma is less responsive to modern therapies than other forms of the syndrome. Possible explanations include its occurrence in older patients frequently in the presence of concomitant interstitial lung disease. It is possible that patients with scleroderma have more severe structural disease of their pulmonary arterioles or have a reduced capacity of their right ventricles to accommodate elevated pulmonary vascular resistance. Earlier diagnosis and intervention should lead to better long term outcomes.
Since patients with scleroderma are typically under care for other scleroderma features, clinical strategies should incorporate early, annual screening for PAH and PH. The elements of screening include a close history talking about level of physical activity and what symptoms limit activity. Unexplained pedal edema or an increased pulmonic valve closure sound (P2) on auscultation are helpful signs.
Most patients with scleroderma have a reduced diffusing capacity either in isolation or in disproportion to reduction in measures of lung volume. Echocardiography with Doppler is a useful screening tool although its accuracy in early, milder pulmonary hypertension or in the setting of concomitant lung disease is less than 50%. Elevated serum NT-proBNP (brain natriuretic peptide) should cause consideration of either right or left ventricular dilatation. Right heart catheterization remains the definitive diagnostic test and permits accuracy in diagnosis as well as exclusion of occult left heart dysfunction.
All patients benefit from simple basic measures including weight loss, attention to fluid balance, agents to improve the efficiency of the heart, e.g., digoxin, supplemental oxygen and anticoagulation (blood thinning). Once medical therapy has been optimized, many patients make significant gains with cardiopulmonary rehabilitation training (CPRT) although this requires close physician guidance.
Recent years have witnessed the development of a variety of treatments that are highly specific to the pathophysiology of PAH. All forms of PAH share evidence of disruption of endothelial function leading to diminished production of the vasodilating prostacyclin and nitric oxide and increased release of the vasoconstrictive endothelin.
Current agents licensed by the U.S. Food and Drug Administration include synthetic prostacyclins; agents that potentiate the effects of nitric oxide (Type V cyclic GMP phosphodiesterase inhibitors); and agents that block the interaction of endothelin with its receptors. Other similar drugs are at late stages of preapproval clinical trials and there is great interest in studying the benefits of various combination therapies. All of these agents are uniquely and specifically suited to the blood vessel issues of PAH.
These agents are very complex and choosing the correct initial treatment requires considerable expertise. Pulmonary Hypertension Centers are important in identifying pulmonary hypertension and in choosing the correct path in treatment.
These drugs are extraordinarily expensive, ranging from $15,000-$150,000 per year. Pharmaceutical benefit issues influence choice of therapy as do specific clinical features in each individual patient. All of these drugs were developed under new government programs that foster drug development for rare or "orphan" diseases. In part, because the "market" is small, the cost per prescription is high.
All of these treatments reduce shortness of breath, improve exercise capacity, and slow the rate of clinical worsening.