Collagen lung disease

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Collagen lung diseases or as they are better known, interstitial lung disease (ILD) includes many disorders.

Interstitial lung diseases are called such because the tissue between the air sacs of the lungs called the interstitium, are affected by fibrosis (scarring).

Interstitial lung diseases (ILD) may also be called interstitial pulmonary fibrosis.

The common link between the many forms of ILD is that they all begin with an inflammation of part of the lung:

bronchiolitis - inflammation that involves the bronchioles (small airways)

alveolitis - inflammation that involves the alveoli (air sacs)

vasculitis - inflammation that involves the small blood vessels (capillaries)

A significant percentage of patients with ILD will have an autoimmune disease responsible for the lung problem.

In interstitial lung disease, the lung is affected because of inflammation and scarring.

Chronic scarring leads to fibrotic lung tissue. Fibrosis results in loss of that tissue's ability to breathe and carry oxygen. Air sacs, as well as the lung tissue between and surrounding the air sacs, and the lung capillaries, are destroyed by the formation of this scar tissue.

The course of ILD is unpredictable.

The following are the most common symptoms for interstitial lung diseases. Symptoms may include:

• shortness of breath
• fatigue
• loss of appetite
• weight loss
• dry cough
• chest tightness
• bleeding into the lungs

The cause of interstitial lung disease in collagen vascular disease is due to the underlying disorder. In addition to a complete medical history and physical examination, other tests may be needed:

pulmonary function tests - to determine characteristics and capabilities of the lungs

blood gases - to analyze the amount of carbon dioxide and oxygen in the blood


computerized axial tomography (CAT) scan


bronchoscopy - to examine the lung using a long, narrow telescope

bronchoalveolar lavage - to remove cells from the lower respiratory tract to aid in diagnosis

lung biopsy

Specific treatment will be determined by:

•overall health and medical history
•extent of the disease
•tolerance for specific medications, procedures or therapies

Treatments may include:

•oral medications, including corticosteroids
•intravenous medications, including immunosuppressive agents or biologic therapies
•influenza vaccine
•pneumococcal pneumonia vaccine
•oxygen therapy from portable tanks
•lung transplantation

An excellent review was published by the Society of Thoracic Radiology…

Pleuropulmonary Manifestations of Collagen Vascular Disease

Gordon L. Weisbrod, M.D., F.R.C.P.C. The University of Toronto

The collagen vascular diseases (CVD) are a heterogenous group of chronic inflammatory and immune-mediated disorders that share certain clinical characteristics, including inflammation of joints and serosal membranes, connective tissues, and blood vessels in various organs. The frequency of thoracic involvement is considerable: Two thirds of 109 patients in one study showed radiological changes in lungs, pleura or heart; pathologic lesions were found at autopsy in 28 of 34 cases in another study.

These disorders frequently manifest distinctive clinical, radiological, and pathological features that permit classification into one disease process. However, considerable overlap may occur, combining features of more than one disease process.

Rheumatoid Arthritis (RA)

In general, most of the pleuro-pulmonary lesions are commoner in males even though rheumatoid arthritis is largely a female disease. The lesions are also commoner in patients with subcutaneous nodules and highly positive tests for rheumatoid factor. The pleuro-pulmonary manifestations are traditionally considered under six headings.

1) Pleuritis and Pleural Effusion

This is the most frequent manifestation; in one series, 21% of 516 patients gave a history of pleurisy and 3.3% had effusion. Low glucose levels are characteristic (under 25mm%) and may be due to defective transport of glucose across the pleural surface membrane. Up to 1/3 of effusions are associated with no respiratory symptoms. They are more commonly unilateral, can be large, and associated parenchymal disease is uncommon.

2) Diffuse Interstitial Disease
In one large series, 1.6% of patients had diffuse interstitial disease radiologically although many more have pulmonary function test abnormalities. A reticulonodular infiltrate is seen, usually worse in the mid and lower lungs. Later, with progressive fibrosis, a course reticular pattern predominates often with honeycombing. The course varies from a few months to many years, ending for some in respiratory failure or cor pulmonale.

3) Necrobiotic Nodules
This is a relatively rare manifestation, appearing as single or multiple peripheral well defined nodules or masses ranging from a few millimeters to several centimeters in diameter, and often resembling metastases. Cavitation occurs in 1/3 to 1/2. The cavities may become infected to form an abscess.
Because the nodules are commonly situated in the periphery of the lung subpleurally and because cavitation is common, rupture into the pleural space may occur with the development of an effusion, empyema, pneumothorax, or bronchopleural fistula.

4) Caplan's Syndrome
This was originally described in 1953 in coal miners in South Wales. The syndrome consists of single or multiple nodules, usually developing rapidly, most often on a background interstitial pattern of coal-workers pneumoconiosis. The nodules often occur concomitantly with the joint changes of rheumatoid arthritis. They may cavitate, increase in size and number, remain unchanged, calcify, or disappear.

5) Pulmonary Arteritis and Pulmonary Hypertension
Narrowing of the pulmonary arteries and arterioles may lead to pulmonary hypertension and cor pulmonale.

6) Bronchiolitis Obliterans
This rare complication of rheumatoid arthritis should be considered in patients with shortness of breath with clear or hyperinflated lungs. No treatment is available and the course is progressively downhill resulting in death. Drug effects must be considered in the differential diagnosis of pulmonary infiltrates in these patients. Gold sodium thiomalate can cause a chronic interstitial pneumonitis, and sometime fibrosis. Penicillamine has also been related to changes in the lungs.

Systemic Lupus Erythematosis (SLE)

The lungs and pleura are involved more frequently in SLE than in any other collagen vascular disease, the incidence varying from 30 to 70%. The radiology can be considered under several categories, one or more being present at any one time.

1) Pleuritis With or Without Effusion
This is the commonest abnormality, being present at some stage in 50 to 75% of patients. The pleural disease is usually painful (as compared with rheumatoid arthritis) and associated with exacerbation of SLE. Effusions are usually bilateral and small.

2) Atelectasis
Areas of discoid atelectasis, usually in the lung bases, and often migratory, are commonly seen. They are frequently associated with pleuritis, effusion, and sometimes diaphragmatic dysfunction.

3) Acute Lupus Pneumonitis
This is a well recognized but very uncommon manifestation of SLE. Radiologically areas of consolidation are seen, usually in the lower lungs, simulating those of infection. The consolidation may become diffuse and extensive and lead to respiratory failure and death in spite of immunosuppressive therapy. The main differential diagnosis clinically and radiologically is that of infection.

4) Interstitial Disease
This is very uncommon in SLE. Radiologically the pattern is similar to that occurring in other collagen diseases such as rheumatoid arthritis and scleroderma. Honeycombing may occur.

5) Diaphragmatic Dysfunction With Loss of Lung Volume
Elevation of the diaphragm with "sluggish movement" and secondary loss of lung volume unshrinking lungs") has been noted in SLE. The inability of the diaphragm to generate normal pressures may be due to a myopathy or immobility and consequent disuse atrophy following extensive pleural adhesions.

7) Infection
This is the commonest abnormality and accounts for about 50% of the pleuropulmonary changes in SLE. Patients on high dose steroid therapy or with renal disease are especially susceptible. Fever and pulmonary involvement in such a patient with SLE should be regarded as presumptive evidence of life-threatening infection until proven otherwise.
The infections may be due to common community-acquired organisms or may be more esoteric reflecting the immunocompromised state.

8) Vasculitis
Vasculitis and pulmonary arterial hypertension are rare manifestations of SLE in the lungs.

Progressive Systemic Sclerosis (PSS)

This is a multisystem disease characterized by varying degrees of vascular change, inflammation and fibrosis of skin and internal organs. In one study, 90% of patients showed morphologic evidence of pulmonary fibrosis at autopsy. The roentgen pattern is one of diffuse reticular interstitial disease, affecting predominantly the lower lobes. Loss of lung volume is a prominent finding. One should also look for bone resorption of the distal clavicles, erosion of the superior cortex of the ribs, and air in the esophagus. The disease progresses at a variable rate and may eventually lead to respiratory failure and Oar pulmonale. Vascular lesions are common in PSS. They consist of intimal thickening of the small and medium sized pulmonary arteries and arterioles with narrowing of the lumina, resulting in pulmonary arterial hypertension. The disturbances in esophageal motility may lead to aspiration pneumonia. There is an increased incidence of bronchogenic carcinoma, especially bronchioloalveolar cell carcinoma in PSS. When respiratory symptoms suddenly worsen or change in PSS, a search should be made for carcinoma.

Polymyositis and Dermatomyositis (PM/DM)

The reported incidence of interstitial lung disease is around 5%. Radiologically, a diffuse reticular or reticulo-nodular infiltrate is seen identical to the other collagen vascular diseases. When polymyositis involves the muscles of respiration, especially the diaphragm, diaphragmatic elevation and small lung volumes are apparent, often in conjunction with atelectasis at the lung bases. This may be severe enough to produce acute respiratory failure. Pharyngeal muscle paralysis may lead to aspiration pneumonia, a frequent terminal event in these patients. The incidence of coexistent carcinoma is probably not as great as is often assumed. Only 16% in one series and 6% in another series had carcinoma. Therefore exhaustive search for malignancy is seldom warranted.

Sjogren's Syndrome (SS)

This is a chronic inflammatory disorder characterized by xerostomia, xerophthalmia, and enlargement of the salivary glands. Pulmonary abnormalities are common in Sjogren's syndrome, varying from 9 to 29%. Lymphocytic infiltration of the mucous glands of the tracheo-bronchial tree with resulting atrophy causes dryness of the mucosa, inspissation of secretions, followed by tracheobronchitis, recurrent infections, and atelectasis. Pneumonia is a common cause of death. Diffuse interstitial fibrosis identical to that in other collagen vascular diseases may occur. A variety of Iymphoproliferative disorders ranging from the benign Iymphocytic interstitial pneumonitis to malignant Iymphoma occur but are very uncommon. Lymphoma usually causes areas of consolidation, nodular or mass-like lesions, and Iymphadenopathy and pleural effusion.

Overlap Syndromes and Mixed Connective Tissue Disease

Overlap syndromes combining features of RA, SLE, PSS, PM-DM have been described. A subgroup of the overlap syndrome has been identified in which antibodies to the ribonucleoprotein component of extractable nuclear antigens are found. This is called mixed connective tissue disease. The pulmonary abnormalities resemble those of SLE, PSS, and PM-DM. Pleural effusion and interstitial lung disease are the commonest. In general, the disease is characterized by an excellent response to steroid therapy.

Ankylosing Spondylitis (AS)

The pulmonary manifestations are principally of two types: chest wall restriction and upper lobe fibrobullous disease. The chest wall restriction is the result of fusion of the costovertebral joints. The resulting impairment of lung function is usually mild. Fibrobullous disease has a reported incidence of 1.3%. The onset ranges from 2 to 38 years after the onset of ankylosing spondylitis. Usually, the disease begins in one upper lobe, but eventually becomes bilateral. The earliest signs are apical pleural thickening and interstitial infiltrate in the lung apex. Cavities or bullae may develop in the areas of fibrosis. The disease may steadily progress or remain stable for years. The fibrosis may become quite extensive, with considerable volume loss and bronchiectasis, simulating tuberculosis. Mycetoma usually of aspergillus, and secondary infection (atypical tuberculosis) may develop in these cavities leading to haemoptysis.


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