Elsevier

Clinics in Chest Medicine

Volume 29, Issue 3, September 2008, Pages 549-563
Clinics in Chest Medicine

Pulmonary Hypertension Caused by Sarcoidosis

https://doi.org/10.1016/j.ccm.2008.03.010Get rights and content

Pulmonary hypertension is an uncommon complication of sarcoidosis, but in severe pulmonary disease it occurs frequently. It is an important cause of cryptogenic dyspnea in sarcoidosis patients and can occur despite the absence of pulmonary fibrosis. The true prevalence is unknown. With the advent of specific therapies for pulmonary hypertension, there has been a resurgence of interest in the pathophysiology, diagnosis, and treatment of sarcoidosis-associated pulmonary hypertension. This article reviews the status of the current epidemiologic, pathophysiologic, and therapeutic knowledge regarding this entity.

Section snippets

History

The modern history of sarcoidosis probably began in 1898, when Hutchinson [11], a London dermatologist, described a case of a patient with “Mortimer's malady,” allegedly a patient with evidence of cutaneous disease. In the initial description, the disease was thought to be a form of cutaneous lupus. Sarcoidosis was recognized as a distinct pathologic entity a year later, when Boeck [12] described the histology of the “sarkoid” granulomas. By 1929, Bernstein [13] had described cardiopulmonary

Epidemiology

The actual prevalence of SAPH has not been established. In patients with significant parenchymal lung disease, the disease was historically thought to be rare, with involvement of the pulmonary vasculature in less than 5% of the cases. Unfortunately, most of the early cohorts were identified retrospectively based on autopsies or case series of patients with clinically diagnosed right heart failure. For example, Mayock and colleagues [20] performed a review of 145 patients with sarcoidosis from

Pathophysiology

The World Health Organization (WHO) currently classifies pulmonary hypertension into five groups, with sarcoidosis included as Class V (miscellaneous) [32]. Compared with idiopathic pulmonary fibrosis, where pulmonary hypertension is probably caused by fibrotic destruction of the distal capillary bed, several mechanisms may be relevant in SAPH. Thus, it is not incorrect to state that the mechanisms for SAPH could be grouped into all five WHO categories [33].

The granulomatous inflammation in

Clinical presentation

Pulmonary hypertension should be suspected in any sarcoidosis patient with dyspnea, hypoxemia, or clinical evidence suggesting right heart failure, particularly if symptoms appear to be out of proportion to the degree of parenchymal lung disease. Unfortunately, these symptoms are often present in patients without PH. Other considerations when patients present with unexplained dyspnea or exercise limitation include myopathy (skeletal or respiratory muscle), large airway obstruction, occult

Management

The optimal management strategy for pulmonary hypertension associated with sarcoidosis is unknown. Treatment has typically involved use of systemic anti-inflammatory medications, anticoagulants, pulmonary vasodilators, endothelin receptor antagonists, and supplemental oxygen. The available literature regarding these therapeutic strategies is limited to small cohort studies, retrospective analyses, and case reports.

Prognosis

Sarcoidosis is generally considered a disease with a favorable long-term prognosis. Although the disease remits spontaneously in nearly two-thirds of patients, about 1% to 5% of patients die from progressive respiratory failure, central nervous system disease, or myocardial involvement [8], [91], [92]. Right ventricular failure has been described in up to 30% of sarcoidosis-related deaths [20], [93]. Patients with substantial pulmonary fibrosis have a particularly elevated risk. A single-center

Summary

The authors conclude that SAPH may be present irrespective of the degree of parenchymal involvement. It may account for a substantial proportion of dyspnea among all sarcoidosis patients, and appears to be common in those with severe parenchymal disease. A major gap in current clinical practice is identification of a cost-effective, reliable, noninvasive method to screen for the presence of SAPH. Further studies are needed to characterize the natural history more closely, to establish whether

References (96)

  • R.P. Baughman et al.

    Right and left ventricular function at rest and with exercise in patients with sarcoidosis

    Chest

    (1984)
  • E.N. Schachter et al.

    Pulmonary granulomas in a patient with pulmonary veno-occlusive disease

    Chest

    (1975)
  • L.J. Smith et al.

    Vascular sarcoidosis: a rare cause of pulmonary hypertension

    Am J Med Sci

    (1983)
  • T.E. Damuth et al.

    Major pulmonary artery stenosis causing pulmonary hypertension in sarcoidosis

    Chest

    (1980)
  • I.R. Preston et al.

    Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension

    Chest

    (2001)
  • R. Bargout et al.

    Sarcoid heart disease: clinical course and treatment

    Int J Cardiol

    (2004)
  • H.J. Kabitz et al.

    Impact of impaired inspiratory muscle strength on dyspnea and walking capacity in sarcoidosis

    Chest

    (2006)
  • A. Chambellan et al.

    Endoluminal stenosis of proximal bronchi in sarcoidosis: bronchoscopy, function, and evolution

    Chest

    (2005)
  • D.A. Zisman et al.

    High-resolution chest CT findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis

    Chest

    (2007)
  • R.P. Baughman et al.

    Six-minute walk test and health status assessment in sarcoidosis

    Chest

    (2007)
  • M. Berger et al.

    Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound

    J Am Coll Cardiol

    (1985)
  • M. McGoon et al.

    Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines

    Chest

    (2004)
  • K.L. Chan et al.

    Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure

    J Am Coll Cardiol

    (1987)
  • P.J. Currie et al.

    Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients

    J Am Coll Cardiol

    (1985)
  • A. Homma et al.

    Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation

    J Heart Lung Transplant

    (2001)
  • E. Bossone et al.

    Echocardiographic features of primary pulmonary hypertension

    J Am Soc Echocardiogr

    (1999)
  • E. Bossone et al.

    Pulmonary arterial hypertension: the key role of echocardiography

    Chest

    (2005)
  • D.M. Rodman et al.

    Successful treatment of sarcoidosis-associated pulmonary hypertension with corticosteroids

    Chest

    (1990)
  • P.F. Castro et al.

    Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium

    Chest

    (1998)
  • H.A. Ghofrani et al.

    Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial

    Lancet

    (2002)
  • K. Jones et al.

    Pulmonary vasodilation with prostacyclin in primary and secondary pulmonary hypertension

    Chest

    (1989)
  • S.M. Palmer et al.

    Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease

    Chest

    (1998)
  • K.A. Fisher et al.

    Sarcoidosis-associated pulmonary hypertension: outcome with long-term epoprostenol treatment

    Chest

    (2006)
  • B.P. Madden et al.

    A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease

    Vascul Pharmacol

    (2006)
  • H.R. Collard et al.

    Sildenafil improves walk distance in idiopathic pulmonary fibrosis

    Chest

    (2007)
  • N.M. Gideon et al.

    Sarcoidosis mortality in the United States 1979–1991: an analysis of multiple-cause mortality data

    Am J Med

    (1996)
  • K. Takada et al.

    The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis

    J Clin Epidemiol

    (1993)
  • M. Sones et al.

    Course and prognosis of sarcoidosis

    Am J Med

    (1960)
  • S.M. Arcasoy et al.

    Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation

    Chest

    (2001)
  • A.F. Shorr et al.

    Predicting mortality in patients with sarcoidosis awaiting lung transplantation

    Chest

    (2003)
  • J.B. Orens et al.

    International guidelines for the selection of lung transplant candidates: 2006 update—a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation

    J Heart Lung Transplant

    (2006)
  • L.J. Henderson

    Blood: a study in general physiology

    (1928)
  • G. Simonneau et al.

    Clinical classification of pulmonary hypertension

    J Am Coll Cardiol

    (2004)
  • M. Humbert et al.

    Pulmonary arterial hypertension in France: results from a national registry

    Am J Respir Crit Care Med

    (2006)
  • R.P. Baughman et al.

    Clinical characteristics of patients in a case control study of sarcoidosis

    Am J Respir Crit Care Med

    (2001)
  • B.A. Rybicki et al.

    Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization

    Am J Epidemiol

    (1997)
  • G.W. Hunninghake et al.

    ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders

    Sarcoidosis Vasc Diffuse Lung Dis

    (1999)
  • J. Hutchinson

    Cases of Mortimer's malady (lupus vulgaris multiplex non ulcerans et non serpiginosis)

    Arch Surg

    (1898)
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    D.A. Culver's work is supported by NIH grant HL081538, from the National Heart Lung and Blood Institute.

    D.A. Culver and J. Parambil are site investigators on an investigator-sponsored trial (Actelion).

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