Elsevier

Clinics in Chest Medicine

Volume 19, Issue 4, 1 December 1998, Pages 713-731
Clinics in Chest Medicine

MANIFESTATIONS OF SCLERODERMA PULMONARY DISEASE

https://doi.org/10.1016/S0272-5231(05)70112-XGet rights and content

Scleroderma (also known as systemic sclerosis) is a disease of unknown cause characterized by the synthesis and deposition of excessive extracellular matrix and vascular obliteration in various organs.7 Although the most common clinical manifestation of scleroderma is hidebound skin, internal organ compromise occurs frequently and is the major determinant of survival.79 Scleroderma (Ssc) has an incidence of approximately 10 cases per million population per year,7 with a range of 1 to 20 new cases per million per year130 and is approximately one-fourth as prevalent as systemic lupus erythematosus (SLE). It is three times more common in women than in men and is slightly more common in blacks than in whites.79, 84, 88 Pulmonary involvement is a significant cause of morbidity and mortality (Table 1) and ranks behind only the skin, peripheral vasculature, and esophagus in frequency of organ involvement.7 Respiratory symptoms were initially attributed to cutaneous changes affecting the chest wall, but in 1898 Von Notthaft154 was the first to conclude that Ssc could directly involve the lungs. Early detection of pulmonary involvement is an important predictor of survival, even in the absence of cardiac and renal involvement.6 Pulmonary complications are the most frequent cause of death in patients with scleroderma7 although only rarely are respiratory symptoms the presenting manifestation, and in these cases occupational exposure (for example to silica) may play a role.81 The most common pulmonary manifestations of scleroderma are pulmonary fibrosis, which occurs in approximately 80% of affected cases, and pulmonary arterial hypertension (PAH), which occurs in approximately 50%.7 Scleroderma is divided into two broad categories on the basis of its clinical features7, 16(Table 2): the limited form, which comprises 60% of cases, usually manifests as the CREST syndrome consisting of calcinosis, Raynaud's phenomenon, esophageal dilatation and dysmotility (Fig. 1), sclerodactyly and telangiectasias; and the diffuse form, which comprises 40% of cases.79 Various circulating antibodies are also found in association with scleroderma although their clinical implications are unknown16, 85, 140, 141(Table 3). (See also the article by Evans in this issue.)

In this article we review the classification of Ssc and the clinical features, pathogenesis, diagnostic modalities, histopathologic characteristics, and management strategies of pulmonary manifestations of this disease.

Section snippets

INTERSTITIAL LUNG DISEASE

Patients with scleroderma develop interstitial lung disease more commonly than patients with any other connective tissue disease.131 Approximately 74% of affected patients are found to have interstitial fibrosis at autopsy.35, 162 Physiologically and histopathologically, scleroderma pulmonary fibrosis resembles idiopathic pulmonary fibrosis.62

Incidence

Depending on the method used to detect PAH and the population under study, the incidence of PAH in patients with scleroderma varies from 6% to 60%.11, 16, 146, 152 Although only 9% of patients with limited cutaneous scleroderma have clinically detectable severe PAH,146 pathology studies show that 65% of these patients have evidence of PAH.166 Ungerer et al152 prospectively studied 49 consecutive patients with scleroderma (39 with diffuse disease and 10 with limited disease). They found definite

LUNG CANCER

Zatucini et al in 1953 were the first to suggest that patients with scleroderma had an increased incidence of lung cancer.167 In 1980, Talbott and Barrocas reviewed the world literature and identified 41 cases of coexisting scleroderma and lung cancer, predominantly bronchoalveolar cell carcinomas.148 In a study of 2141 patients, Duncan and Winkelman41 reported an overall cancer rate of 4% and no increase in the incidence of lung cancer compared with the general population. However, other

OTHER MANIFESTATIONS

Asymptomatic bronchiolitis is a common finding in patients with scleroderma.19 Recently, two cases of bronchiolitis obliterans organizing pneumonia, associated with limited scleroderma, have been reported.20

Diffuse alveolar hemorrhage is a rarely reported consequence of scleroderma,56, 80 and immune complexes are thought to play an important etiologic role in its pathogenesis. Capillaritis and focal fibrinoid necrosis of alveolar walls are seen on microscopy.96

Groen et al in 199357 were the

CONCLUSIONS

Pulmonary involvement in scleroderma is not an unusual occurrence and is a significant cause of morbidity and mortality. Pulmonary fibrosis and PAH constitute the most common manifestations. A multifactorial process involving alveolitis, stepped-up lung fibroblast proliferation, and capillary endothelial damage is responsible. Symptoms and signs, though often present, are nonspecific. Pulmonary function testing often reveals a restrictive ventilatory defect with a decreased DLCO. Aims of

References (168)

  • G.I. Greenwald et al.

    Longitudinal changes in lung function and respiratory symptoms in progressive systemic sclerosis

    Am J Med

    (1987)
  • H. Groen et al.

    Interstitial lung disease and myositis in a patient with simultaneously occurring sarcoidosis and scleroderma

    Chest

    (1993)
  • N.K. Harrison et al.

    Pulmonary involvement in systemic sclerosis: The detection of early changes by thin section CT scan, bronchoalveolar lavage and TC-DTPA clearance

    Respir Med

    (1989)
  • C.G.M. Kallenberg et al.

    The steroid responsive interstitial pulmonary disease in systemic sclerosis

    Chest

    (1984)
  • G.C. Kane et al.

    Lung involvement in systemic sclerosis (scleroderma): Relation to classification based on extent of skin involvement or autoantibody status

    Respir Med

    (1996)
  • J.H. Kim et al.

    Endobronchial telangiectasias and hemoptysis in scleroderma

    Am J Med

    (1988)
  • C. Kostopoulos et al.

    Small airway dysfunction in systemic sclerosis. A controlled study

    Chest

    (1992)
  • E.L. Kramer et al.

    Pulmonary application of nuclear medicine

    Clin Chest Med

    (1991)
  • E.C. LeRoy

    Pulmonary hypertension: The bete noire of the diffuse connective tissue diseases

    Am J Med

    (1991)
  • C. Lombardi et al.

    Systemic sclerosis, small airway dysfunction and bronchial hyper-reactivity [letter]

    Chest

    (1994)
  • R.M. Lomeo et al.

    Progressive systemic sclerosis sine scleroderma presenting as pulmonary interstitial fibrosis

    Am J Med

    (1989)
  • D. Mahler et al.

    Measurement of respiratory sensation in interstitial lung disease

    Chest

    (1989)
  • E. Martinez-Cordero

    Antinuclear antibodies associated with pulmonary involvement in systemic sclerosis

    Chest

    (1989)
  • T.A. Medsger et al.

    Epidemiology of progressive systemic sclerosis

    Clin Rheum Dis

    (1979)
  • D.S. McCarthy et al.

    The lung in systemic sclerosis (scleroderma): A review and new information

    Semin Arthritis Rheum

    (1988)
  • J.M. Morgan et al.

    Hypoxic pulmonary vasoconstriction in systemic sclerosis and primary pulmonary hypertension

    Chest

    (1991)
  • A.P. Niarchos et al.

    Hemodynamic effects of captopril in pulmonary hypertension of collagen vascular disease

    Am Heart J

    (1982)
  • K. Nishi et al.

    Diffuse cutaneous systemic sclerosis associated with pan-serositis, disseminated intravascular coagulation and diffuse alveolar hemorrhage

    Respir Med

    (1994)
  • J.T. O'Brien et al.

    Sustained benefit of verapamil in pulmonary hypertension with progressive systemic sclerosis

    Am Heart J

    (1985)
  • J. Ohar et al.

    The role of vasodilators in patients with progressive systemic sclerosis: Interstitial lung disease and pulmonary hypertension

    Chest

    (1985)
  • G.R. Owens et al.

    Pulmonary function in progressive systemic sclerosis. Comparison of CREST syndrome variant with diffuse scleroderma

    Chest

    (1983)
  • M. Abu-Shakra et al.

    Cancer in systemic sclerosis

    Arthritis Rheum

    (1993)
  • P.K. Adhikari et al.

    Pulmonary function in scleroderma: Its relation to changes in chest roentgenogram and in the skin of the thorax

    American Review of Respiratory Disease

    (1962)
  • A. Akesson et al.

    Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide

    Arthritis Rheum

    (1994)
  • M.R. Al-Sabbagh et al.

    Pulmonary arterial histology and morphometry in systemic sclerosis: A case controlled autopsy study

    J Rheumatol

    (1989)
  • R.D. Altman et al.

    Predictors of survival in systemic sclerosis (scleroderma)

    Arthritis Rheum

    (1991)
  • A.C. Arroliga et al.

    Pulmonary manifestations of scleroderma

    Journal of Thoracic Imaging

    (1992)
  • L.R. Bagg et al.

    Serial pulmonary function tests in progressive systemic sclerosis

    Thorax

    (1979)
  • M. Baron et al.

    67-gallium lung scan in progressive systemic sclerosis

    Arthritis Rheum

    (1983)
  • M. Baron et al.

    Effects of prostaglandin E1 and other vasodilator agents in pulmonary hypertension of scleroderma

    British Heart Journal

    (1982)
  • J. Behr et al.

    Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung

    Am J Respir Crit Care Med

    (1996)
  • A. Bergemann et al.

    Cystic lung disease in systemic sclerosis: A case report with high resolution computed tomography findings

    Rev Rhum (Engl Ed)

    (1996)
  • B. Blom-Bulow et al.

    Lung function in progressive systemic sclerosis is dominated by poorly compliant lungs and stiff airways

    European Journal of Respiratory Disease

    (1985)
  • J.A. Boyd et al.

    Roentgen changes observed in generalized scleroderma: Report of 63 cases

    Arch Intern Med

    (1954)
  • S.N. Breit et al.

    The presence of Sjögrens syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue disease

    J Rheumatol

    (1989)
  • A.J. Bridges et al.

    Bronchiolitis obliterans organizing pneumonia and scleroderma

    J Rheumatol

    (1992)
  • D. Briggs et al.

    A molecular and serologic analysis of the major histocompatibility complex and complement component C4 in systemic sclerosis

    Arthritis Rheum

    (1993)
  • J.B. Cailes et al.

    Neutrophil activation in fibrosing alveolitis: A comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis

    Eur Respir J

    (1996)
  • D. Cairns et al.

    The differing patterns of interstitial lung involvement in connective tissue diseases

    J Rheumatol

    (1992)
  • J.A. Casas et al.

    5-Fluorouracil in the treatment of scleroderma: A randomized, double-blind, placebo controlled international collaborative study

    Ann Rheum Dis

    (1990)
  • Cited by (0)

    Address reprint requests to Alejandro C. Arroliga, MD, Department of Pulmonary and Critical Care Medicine, G-62, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195

    View full text