Lung Involvement in Scleroderma

doi:10.1378/chest.85.3.318

Chest

Volume 85, Issue 3, March 1984, Pages 318-324

https://doi.org/10.1378/chest.85.3.318 Get rights and content

Lung involvement (LI) was studied by lung function (LF) in 101 scleroderma patients (circumscribed scleroderma, n = 17; progressive systemic scleroderma [PSS], n = 84; with the subtypes I, acroscleroderma [n=19]; 2, proximal ascending scleroderma [n=61]; 3, trunk scleroderma [n=4]). Eighteen percent of morphea, 32 percent of type 1, 56 percent of type 2, and 75 percent of type 3 patients had impaired LE The LI was more frequent (57 percent vs 45 percent) and more severe (20 percent vs 3 percent) in PSS with systemic inflammation (form A) compared to those without (form B). Elevated lymphocytes/neutrophils in bronchoalveolar lavage (BAL) were found associated with form A and severe LI. The LF of patients showing an inflammatory cell pattern in initial BAL (n=3) worsened, whereas those with normal BAL findings (n=4) did not. Collagenase activity in BAL was significantly elevated in those with elevated lymphocytes/neutrophils in lavage. Patients with type 2 or 3 of PSS, especially form A, carry a higher risk of developing severe LI than circumscribed scleroderma, type 1, or form B patients. Differential cell count and collagenase activity in BAL is correlated with active disease and provides prognostic information.

Section snippets

Patients

One hundred and four patients (30 men, 74 women; aged 18 to 78 years, mean 47.0 ± 12.8 years, M ± SD) with clinical and histologic evidence of scleroderma were included in the study. These patients were seen in the years 1979 to 1982. Each patient underwent dermatologic staging, skin biopsies, and a clinical investigation especially from the point of view of internal-pulmonary medicine. The PSS as diagnosed and typed according to clinical picture and symptoms in agreement with the proposals of

RESULTS

Of the 101 patients who were finally considered, 54 percent had normal, 26 percent mild, 10 percent moderate, and 10 percent severely reduced lung function which was characteristic for interstitial lung disease.

Frequency, as well as severity of pulmonary functional impairment was related to the clinical type of scleroderma (Table 2). The vast majority of patients in the groups circumscribed scleroderma and type 1 PSS had normal and none had severely impaired lung function. In contrast, most

DISCUSSION

In general terms, we have confirmed the previous findings28, 29, 30 that lung function in severe pulmonary PSS shows the typical pattern of interstitial lung disease with decrease of lung volumes and CO-transfer factor, as well as hypoxemia at rest and during exercise in the absence of bronchial obstruction.

In a seven-year study including 309 patients, Medsger et al³¹ found lung involvement as well as heart and kidney manifestation to be one of the life limiting complications in scleroderma.

ACKNOWLEDGMENT

G. Heinz, C. Lehr, E. Miller, E. Simon and A. Wielath provided technical assistance, and C. Fink, secretarial assistance.

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Cited by (53)

Bronchoalveolar Lavage Fluid in Scleroderma Interstitial Lung Disease: Technical Aspects and Clinical Correlations: Review of the Literature
2010, Seminars in Arthritis and Rheumatism
Citation Excerpt :
For the purpose of this review, only those clinical studies that included more than 15 patients and aimed at evaluation of the relationships between the BAL fluid differential cell count analysis and clinical status of the patients were selected. Nineteen studies fulfilled the selection criteria and are included in the analysis (6-26) (Table 1). Additional references pertaining to the research aspects of BAL in SSc-ILD are also reviewed.
Bronchoalveolar lavage (BAL) has been used for clinical and research purposes in scleroderma interstitial lung disease (SSc-ILD). However, inconsistencies regarding technical aspects of BAL are obstacles in the reproducibility and interpretation of BAL results. This review summarizes clinical correlations and methodological issues of using BAL in the assessment of patients with SSc-ILD. In addition, we review the investigational use of BAL in SSc-ILD.
The PubMed database from inception through May 2008 was searched using the following keywords: “systemic sclerosis, scleroderma, interstitial lung disease, and bronchoalveolar lavage.” The search was limited to English-language studies that included at least 15 SSc patients that had BAL.
An increased percentage of neutrophils, eosinophils, and/or lymphocytes, often referred to as “alveolitis,” was reported in a significant percentage of SSc patients (range, 38 to 100%) irrespective of patient selection criteria, cytological cutoff values, or technical aspects of BAL processing. Alveolitis is associated with more severe lung impairment as defined by lung function tests and overall lung high-resolution computed tomography scores, but there is insufficient evidence at this time to recommend BAL cytology as an independent predictor of outcome in SSc-ILD patients. Myofibroblasts have been cultured from BAL fluid, and inflammatory and fibrogenic mediators can be measured in the supernatant of BAL fluid from patients with SSc-ILD.
Further studies using standardized BAL protocols are required to establish the role of BAL fluid in the clinical evaluation of SSc-ILD. When performed for research purposes, BAL has provided valuable insight into the pathogenesis of SSc-ILD.
Uncommon causes of cough: ACCP evidence-based clinical practice guidelines
2006, Chest
To describe the uncommon causes of cough.
An English language literature search by MEDLINE citations from 1975 through 2004 was used to identify publications on uncommon pulmonary and nonpulmonary disorders in which cough was present as the major or presenting symptom in > 50% of those persons affected by the uncommon diseases.
A substantial number of uncommon or rare pulmonary and nonpulmonary disorders were identified. The uncommon occurrence of these diseases made it difficult to develop a meaningful evidence-based guideline to the diagnosis and therapy of many of the uncommon causes of cough. As cough was the major or presenting symptom, it was usually initially attributed to common respiratory diseases (eg, asthma or bronchitis). As a result, a substantial time lag existed from the onset of cough to the diagnosis of the etiologic entity. Diagnostic tests limited to the respiratory system did not always provide clues to the diagnosis of uncommon causes of cough.
Cough is the major or presenting symptom in many uncommon pulmonary and nonpulmonary disorders. A strong index of suspicion is essential to consider and diagnose the uncommon causes of cough. The diagnosis and management of cough in patients with uncommon causes of cough is dependent on the underlying etiology.
Pulmonary function tests in interstitial lung disease: What role do they have?
2001, Clinics in Chest Medicine
Organizing diffuse alveolar damage associated with progressive systemic sclerosis
1997, Mayo Clinic Proceedings
Diffuse alveolar damage (DAD) is a relatively nonspecific pattern of acute lung injury that can be observed in a wide range of clinical circumstances. DAD has often been recognized in association with various connective tissue diseases; however, to our knowledge, it has not been previously reported in the setting of progressive systemic sclerosis. Herein we describe two patients with established diagnoses of progressive systemic sclerosis who had development of the acute respiratory distress syndrome. Open-lung biopsy specimens from both patients showed a histologic pattern of DAD with no identifiable cause other than their progressive systemic sclerosis. Our results suggest that DAD should be added to the list of pleuro-pulmonary complications of progressive systemic sclerosis.
Cardiorespiratory responses to incremental exercise in patients with systemic sclerosis
1996, Chest
Patients with systemic sclerosis are known to have histologic pulmonary abnormalities despite normal chest radiograph or conventional pulmonary function or both. In an attempt to detect early features of lung involvement in progressive systemic sclerosis, we investigated patients with systemic sclerosis using cardiopulmonary exercise testing. We have studied 78 patients who fulfilled the American Rheumatism Association criteria for the classification of systemic sclerosis, and according to the classification of LeRoy, 44 had limited cutaneous systemic sclerosis and 34 had diffuse cutaneous systemic sclerosis. A significantly decreased diffusing capacity (65±3% of that predicted) was present only in the group with diffuse cutaneous systemic sclerosis. The patients with lung involvement showed a significant reduction in exercise capacity (54±3% of that predicted) and in oxygen uptake (70±3% of that predicted). Additionally, we could demonstrate an increased functional dead space ventilation (0.34±0.02) and widened alveolar-arterial oxygen difference during exercise (44±3 mm Hg). By cardiopulmonary exercise testing, 12 of the 78 patients (15%) with normal single-breath diffusing capacity for carbon monoxide had increased dead space to tidal volume ratio. Our results suggest that occult pulmonary impairment may be present in patients with normal pulmonary function and that cardiopulmonary exercise testing enables detection of such impairment. Our study results show the limitations of resting data in predicting abnormalities during exercise in patients with systemic sclerosis.
Clinical problems. The lungs
1996, Rheumatic Disease Clinics of North America
Pulmonary manifestations of systemic sclerosis (SSc, scleroderma) are manifold (Table 1) and often have a profound influence on the course of the disease. A discussion of all the pulmonary complications of SSc is beyond the scope of this article but is presented in a recent review.¹⁰ The two major pulmonary conditions occurring among SSc patients, pulmonary hypertension and interstitial fibrosis (Table 2), will be discussed in detail. Isolated pulmonary hypertension occurs primarily in patients with limited cutaneous SSc (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia [CREST] variant) in the absence of significant pulmonary fibrosis, whereas interstitial fibrosis occurs in either limited or diffuse cutaneous SSc.

View all citing articles on Scopus

This work was supported by the Deutsche Forschungsgemeinschaft

Manuscript received June 7; revision accepted August 17.

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Chest

Lung Involvement in Scleroderma

Section snippets

Patients

RESULTS

DISCUSSION

ACKNOWLEDGMENT

Am J Med

Chest

J Chron Dis

Chest

Histologic diagnosis of inflammatory skin diseases

Cellular infiltrates in scleroderma skin

Arthritis Rheum

Connective tissue synthesis by scleroderma skin fibroblasts in cell culture

J Exp Med

Scleroderma fibroblasts: some aspects of in vitro assessment of collagen synthesis

Arch Dermatol Res

The connective tissue of lung

Am Rev Respir Dis

Lung function in patients with systemic sclerosis

Thorax

Pulmonary function in scleroderma

Thorax

The pathophysiology of scleroderma involving the heart and respiratory system

Ann Intern Med

The lung in scleroderma

Mayo Clin Proc

Pathogenesis and staging of scleroderma

Acta Dermatovener (Stockholm)

Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage

Am J Pathol

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis

J Clin Invest

Idiopathic pulmonary fibrosis: clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects

Ann Intern Med

Cells, collagen and idiopathic pulmonary fibrosis

Lung

Morphology and therapeutic chances of interstitial lung disease

Respiration