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Pulmonary hypertension complicating sarcoidosis

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Summary

Pulmonary hypertension is a challenging complication of sarcoidosis, which reported rates of prevalence largely depend on the advancement of pulmonary disease. About 6% of unselected sarcoidosis patients suffer from PH. Although destruction of the distal capillary bed and resultant hypoxemia are important, the mechanisms of sarcoidosis-PH are multifactorial, including specific vasculopathy, local increased vasoreactivity, extrinsic compression of pulmonary vessels and portal hypertension. As a result, a proportion of patients exhibit “out of proportion” PH, i.e. more severe than expected from functional impairment (mean PAP > 35–40 mmHg). The sarcoidosis vasculopathy prevails in the venous side, reflecting the spreading of granulomatous process, and can cause pulmonary veno-occlusive disease. The responsibility of left-heart dysfunction is probably underestimated by echocardiography. There is no validated screening algorithm for the detection of sarcoidosis-PH but recent studies have underlined the role of right heart catheterisation to exclude post-capillary PH. PH carries a poor prognosis in sarcoidosis patients, with a significantly increased morbidity and mortality. Management of sarcoidosis-PH mainly relies on supportive therapy (supplemental oxygen and diuretics as needed) and lung transplantation in otherwise eligible patients. Rare cases of sarcoidosis-PH with nonfibrotic pulmonary disease respond to corticosteroids. Data on the efficacy and safety of PAH agents are scarce and discrepant. Further controlled trials are warranted and should integrate the concept of disproportionate PH in their design.

Section snippets

Classification of pulmonary hypertension and concept of “out of proportion” pulmonary hypertension

PH is defined by an increased mean pulmonary arterial pressure (mPAP) greater or equal to 25 mmHg at rest on right heart catheterisation (RHC). In an attempt to assist physicians on their clinical practice, an updated clinical classification of PH derived from the Dana Point meeting has been published in 2009 (box 1) [2]. Group 3 refers to “PH due to lung diseases and/or hypoxia”, including interstitial lung diseases (ILDs). Group 5 has been created for “PH with unclear and/or multifactorial

Frequency of sarcoidosis-associated PH

The exact prevalence of PH complicating sarcoidosis remains to establish. The wide distribution in published rates is most likely due to the use of different measurement techniques, selection of diverse patient populations or various stages of disease (table I). Overall, PH affects 1% to 6% patients with sarcoidosis [4], [5], [6], [7], [8] but it is much more frequent in advanced lung disease [9] or in symptomatic patients [10].

The only available prospective study conducted by Handa et al. has

Pathogenesis of sarcoidosis-associated PH

As already indicated above, sarcoidosis is classified in the group 5 of PH classification but essentially, the mechanisms of sarcoidosis-associated PH may fit into all five categories [2], [3].

Diagnosis of sarcoidosis-associated PH

The clinical picture of underlying respiratory disorder can mask PH and delay its recognition. Several symptoms should, yet, prompt diagnostic intervention: dyspnoea more severe than one would expect from functional impairment, chest pain, palpitations, near syncope on exertion. Physical signs include a loud P2 component to the second heart sound, a fixed, split S2, a holosystolic murmur of tricuspid regurgitation (TR) and a diastolic murmur of pulmonic regurgitation. About one quarter of

Screening of sarcoidosis-associated PH

As PH bears a severe prognosis in sarcoidosis, early diagnosis and consideration of treatment options may be keys to improve patients’ outcome. Nonetheless, there is no consistent single clinical criteria that can be used to adequately segregate sarcoidosis patients with a high or low risk for PH. Owing the limited accuracy of TTE, this should not serve as the only guide to determine who requires further invasive intervention. In light of recent data, RHC seems particularly important in

Clinical impact and prognosis of sarcoidosis-associated PH

PH is a debilitating condition in sarcoidosis patients, which accounts for refractory dyspnoea [10] and reduced exercise capacity [12], [59]. Additionally, the burden of PH on functional status and employment status is substantial [9]. Transplantation candidates with PH are more likely to need some or total assistance with their activities of daily living (nearly 70% of those with mPAP  40 mmHg) and PH increases the risk of being unemployed due to disease [9]. Furthermore, PH is well known to

Treatment of sarcoidosis-associated PH

In view of limited publications, no recommendation can be drawn on the optimal therapeutic strategy for sarcoidosis-associated PH, which should take into account the prominent underlying mechanism of PH. Obviously, supportive therapy is the cornerstone of management, including supplemental oxygen in patients who are hypoxemic at rest or during exercise and diuretics as needed.

With respect to therapy directed to sarcoidosis, published results are somewhat discrepant. PH can worsen despite

Conclusion

PH is a challenging complication of sarcoidosis both in terms of diagnosis and management. There are recent shreds of evidence suggesting that sarcoidosis-associated PH may be more complex than just the result of parenchymal lung disease and hypoxemia. Intrinsic vasculopathy may play an important role. The presence of PH signifies a grave prognosis in patients with sarcoidosis. PAH-targeted therapy is tempting in sarcoidosis-associated PH but the lack of conclusive data leaves many

Disclosure of interest

the authors declare that they have no conflicts of interest concerning this article.

Glossary

CCB
calcium channel blockers
ILDs
interstitial lung diseases
IPF
idiopathic pulmonary fibrosis
PAH
pulmonary arterial hypertension
PH
pulmonary hypertension
PVOD
pulmonary veno-occlusive disease
PWP
pulmonary wedge pressure
RHC
right heart catheterisation

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