Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis

Abstract

Background: Pulmonary hypertension (PH) is a rare complication of sarcoidosis, although it is not uncommon in advanced disease. Methods: A retrospective series of 22 sarcoidosis patients (16 men) of mean (SD) age 46 (13) years with PH was divided into two groups depending on the absence (stage 0: n = 2, stage II: n = 4, stage III: n = 1) or presence (n = 15) of radiographic pulmonary fibrosis at the time of PH diagnosis. Results: In both groups PH was moderate to severe and there was no response to acute vasodilator challenge. In non-fibrotic cases no other cause of PH was found, suggesting a specific sarcoidosis vasculopathy, although no histological specimens were available. In cases with fibrosis there was no correlation between haemodynamics and lung volumes or arterial oxygen tensions, suggesting other mechanisms for PH in addition to pulmonary destruction and hypoxaemia. These included extrinsic arterial compression by lymphadenopathies in three cases and histologically proven pulmonary veno-occlusive disease in the five patients who underwent lung transplantation. Ten patients received high doses of oral prednisone for PH (stage 0: n = 1, stage II: n = 4 and stage IV: n = 5); three patients without pulmonary fibrosis experienced a sustained haemodynamic response. Survival of the overall population was poor (59% at 5 years). Mortality was associated with NYHA functional class IV but not with haemodynamic parameters or with lung function. Conclusion: Two very different phenotypes of sarcoidosis combined with PH are observed depending on the presence or absence of pulmonary fibrosis. PH is a severe complication of sarcoidosis.

Pathogenesis of pulmonary hypertension: a case for caveolin-1 and cell membrane integrity

“…Since inflammation induces the activation of ECs leading to endothelial dysfunction, it is not surprising that inflammation plays a significant role in the pathogenesis of PH. Patients with underlying inflammatory and autoimmune diseases such as scleroderma (75), polyneuropathy, organomegaly, endocrinopathym M-protein, skin abnormalities (POEMS) syndrome (71), acquired immunodeficiency syndrome (21), sarcoidosis (94), and schistosomiasis (66) have a propensity to develop PH. Furthermore, patients with PH exhibit perivascular infiltrates of inflammatory cells (126), regulated on activation, normal T cell expressed and secreted (RANTES) associated with CD45 ϩ inflammatory cells (26), and increased circulating levels of proinflammatory cytokines such as IL-1, IL-6 (51), fractalkine (7), and monocyte chemoattractant protein-1, currently known as chemokine (C-C motif) ligand 2 (57).…”

Severe pulmonary arterial hypertension as a predominant manifestation of angioimmun- oblastic T-cell lymphoma: a case report

“…PAH is also presumed to occur secondary to the extrinsic compression of the main pulmonary arteries by swollen mediastinal lymph nodes [9] . Although mediastinal lymph node swelling was observed in this case, no changes in the diameters of the pulmonary hilar arteries were observed on CT images after chemotherapy, compared with the initial state, enabling this possible cause to be ruled out.…”

Pulmonary veno-occlusive disease: advances in clinical management and treatments

“…However, we have reported the same proportion of hemoptysis in idiopathic PAH and PVOD, even with the use of anticoagulation. As in idiopathic PAH, no data support the role of immunosuppressive therapy in idiopathic PVOD, but it may be of interest in PAH or PVOD associated with other inflammatory conditions, including sarcoidosis, mixed connective tissue disease and systemic lupus erythematosus, but not in scleroderma-associated PAH [14,74,75].…”

“…PVOD is also thought to be present in some cases of pulmonary hypertension patients displaying sarcoidosis. However, in these patients, the pulmonary vascular component may be less responsive to treatment with glucocorticoids than the parenchymal lung disease [14]. There has been mounting evidence that PAH has a significant inflammatory component [90], and that PAH seen in some connective tissue diseases responds well to immunosuppressive therapy [75,80,89].…”

“…PVOD can also occur in conditions usually associated with pulmonary hypertension including connective tissue diseases [11][12][13], sarcoidosis [14], pulmonary Langerhans cell histiocytosis [7,15,16] and, more rarely, HIV infection [17][18][19].…”