Clinical History
A 29-year-old female patient presented with progressive dyspnoea on exertion (NYHA class 3) and cough. She denied chest pain, orthopnoea, or paroxysmal nocturnal dyspnoea, or any history of deep vein thrombosis or other thromboembolic disease. She also denied exposure to toxic inhalants, cigarette smoking, or use of appetite suppressants.
Imaging Findings
On admission to hospital, blood gas analysis was indicative of hypoxaemia. Chest radiograph demonstrated dilation of central pulmonary vasculature and enlarged heart with no parenchymal abnormalities (figure 1). Contrast-enhanced CT showed enlargement of central pulmonary arteries with no evidence of intraluminal thrombus, excluding pulmonary thromboembolic disease (confirmed by ventilation/perfusion scan) (figure 2). Chest CT on lung windows showed smooth thickening of interlobular septa, small ill-defined centrilobular nodules and some regions of ground-glass opacity - inhomogeneous attenuation of lung parenchyma, but no evidence of chronic obstructive pulmonary disease or pulmonary fibrosis (figure 3).
Transthoracic echocardiordiogram demonstrated enlargement of the right chambers with normal left ventricular systolic function but diastolic dysfunction due to RV compression.
Right heart catheterization demonstrated high mPAP (90mmHg) and PCWP (20mmHg), cardiac output (2, 3l/min) and elevated pulmonary vascular resistance.
To exclude a secondary cause of pulmonary hypertension she underwent a lung biopsy that revealed granulomatous vasculitis compatible with sarcoidosis.
Discussion
Pulmonary hypertension (PH) is defined haemodynamically by right heart catheter measurements of a mPAP ≥ 25 mm Hg at rest, with a PCWP ≤ 15 mm Hg and pulmonary vascular resistance ≥ 3 Wood units [1].
PH is a well recognized complication of sarcoidosis occurring in 4-28% of patients and occurs commonly in patients with advanced pulmonary sarcoidosis [2, 3]. The pathophysiology of sarcoidosis-related PH (SAPH) is complex and includes multiple potential mechanisms: fibrous destruction of the pulmonary vascular bed, extrinsic compression of the central pulmonary vessels, hypoxic pulmonary vasoconstriction, pulmonary vascular remodelling, intrinsic pulmonary vasoreactivity, pulmonary veno-occlusive disease (PVOD), myocardial dysfunction, porto-pulmonary hypertension and an intrinsic sarcoid vasculopathy [2, 4]. Therefore PH is not always associated with overt parenchymal involvement, with 40–60% of patients with SAPH having no radiographic evidence of pulmonary fibrosis [2, 4].
The classification of PH was revised at the World Symposium on Pulmonary Arterial Hypertension in Dana Point. As the pathogenesis of PH in sarcoidosis is complex and multifactorial, sarcoidosis is included in the fifth ‘miscellaneous’ group [1].
Patients with SAPH have poorer functional status and greater supplemental oxygen requirements than sarcoid patients without PH, are more likely to be listed for lung transplantation and have a 10-fold increase in mortality over those with isolated pulmonary sarcoidosis. Moreover, SAPH in the absence of pulmonary fibrosis may be a more rapidly progressive disorder, with higher pulmonary vascular resistance levels.
Current therapeutic recommendations include the reversal of resting hypoxaemia, treatment of comorbidities and treatment of underlying sarcoidosis. Specific PH therapy is not routinely recommended in SAPH but there are some studies that found that PAH-specific therapy may improve functional class, exercise capacity, and haemodynamics in PH associated with sarcoidosis [5].
In this case a fortuitous association between sarcoidosis and idiopathic PH cannot be definitively ruled out but seems unlikely because of the low incidence of each disease.
High-dose corticosteroid therapy was initiated, together with supplemental oxygen therapy and epoprostenol iv. The patient was referred to a lung transplant centre for evaluation.
Differential Diagnosis List
Pulmonary hypertension secondary to sarcoidosis
Idiopathic pulmonary arterial hypertension
Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis
Final Diagnosis
Pulmonary hypertension secondary to sarcoidosis
