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

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    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

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