Interstitial Lung Disease Associated With Collagen-Vascular Disease Clinical Presentation

Updated: Sep 10, 2019
  • Author: Isabel F Pedraza, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Presentation

History

A thorough history is key for the diagnosis of collagen-vascular diseases (CVDs). It should include present symptoms, the onset and duration of symptoms, other body systems involvement (other than the lungs), and past medical conditions. A careful history of occupation, environmental exposures, smoking, radiation exposure, and drug use is needed to make a correct diagnosis. Extrapulmonary symptoms should be sought. These may include, but are not limited to rashes, telangiectasias, skin thickening, and nail pitting (can be found in scleroderma); musculoskeletal or joint pain (can be found in RA); and Raynaud symptoms.

A history of smoking is important because it can exacerbate the underlying CVD. A detailed history of previously used medications is needed to exclude the possibility of drug-induced lung disease. Certain CVDs (eg, systemic lupus erythematosus [SLE]) run in families, and a detailed family history is important in these cases. A patient’s previous employment history and environmental exposures may be helpful to differentiate CVD from interstitial lung disease (ILD) secondary to occupational exposure.

The clinical manifestations of CVD depend on the underlying CVD (see below); as a group, almost all CVDs cause diffuse ILD. Predominant symptoms of all CVDs include an insidious onset of dyspnea, cough, hypoxia, and, in the later stages of ILD, hypoxemia. Occasional chest pain is also reported.

Systemic lupus erythematosus

The clinical diagnosis of SLE is based on the presence of at least 4 of the following 10 features:

  • Rash

  • Discoid lupus

  • Photosensitivity

  • Oral ulcers

  • Arthritis

  • Serositis

  • Renal disorders

  • Neurologic disorders

  • Hematologic disorders

  • Immunologic disorders

SLE can involve any part of the respiratory system [36] and can cause acute pneumonitis (in 1-9% of cases), ILD (25%), pleuritis and pleural effusions (50-80%), an increased incidence of bacterial pneumonia, diffuse alveolar damage (1-2%), pulmonary hypertension (9%) and thromboembolism, diaphragmatic dysfunction with reduced lung volumes, [47] shrinking lung syndrome, and acute reversible hypoxemia syndrome. [48]

Pleural disease is the most common lung abnormality; pleural effusion occurs in 50-70% of cases. [49] Effusions are usually small, bilateral, and exudative. Fibrothorax due to lupus pleuritis is a rare complication.

Pneumonia, usually of bacterial origin, is the most common cause of pulmonary infiltrates in SLE patients. It may be related to immunosuppression by the disease itself or may be due to the drug treatment. Lupus pneumonitis occurs in 5% of cases and is characterized by fever, cough, pleurisy, dyspnea, pulmonary infiltrates on radiography, hypoxia, and pleural effusion.

Diffuse alveolar hemorrhage (DAH) [50] due to capillaritis is rare (occurring in 1-2% of cases) and is associated with a high mortality. It is characterized by fever, cough, dyspnea, hypoxia, and hemoptysis. The presentation is similar to that of acute lupus pneumonitis; however, in DAH, the diffusion capacity of the lung for carbon monoxide (DLCO) is usually high, and lupus nephritis is present. Diagnosis is typically made by bronchoscopy with bronchoalveolar lavage, which shows progressively bloody lavage fluid and hemosiderin-laden macrophages.

Diaphragmatic dysfunction or pleuritic chest pain with restriction of respiration has been suggested but not confirmed as a cause shrinking lung syndrome. Patients have shortness of breath, and chest radiographs show loss of lung volume with no evidence of interstitial fibrosis or significant pleural disease. Furthermore, patients with chronic interstitial pneumonitis usually present with an insidious onset of dyspnea, chronic hypoxia, nonproductive cough, and recurrent pleuritic chest pain.

Pulmonary hypertension is less common with SLE than with other CVDs (eg, scleroderma [SD] or mixed connective-tissue disease [MCTD]). Symptoms of pulmonary hypertension include dyspnea (which increases with exercise), fatigue, weakness, and right-side heart failure.

Acute reversible hypoxemia is rare in SLE patients; it manifests as acute hypoxia with negative chest radiography findings and no evidence of pulmonary emboli. Pulmonary leukoaggregation and complement activation are thought to be the causes of this acute hypoxemia. Antiphospholipid antibodies can cause thromboembolic events in patients with SLE.

See Systemic Lupus Erythematosus for more information.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is commonly associated with pleural disease (in 20-40% of cases), interstitial pneumonitis (5-10%), nodules (1%), interstitial fibrosis (similar to interstitial pulmonary fibrosis [IPF]), bronchiolitis obliterans organizing pneumonia (BOOP), and pulmonary vasculitis. Pleural effusions in RA, unlike those in SLE, are usually small, unilateral, and asymptomatic.

ILD occurs most commonly in middle-aged men and is usually associated with severe arthritis and high serum levels of rheumatoid factor (RF). Risk factors include male sex, older age, and a history of cigarette smoking. Clinically, patients develop an insidious onset of dyspnea with occasional dry cough. The underlying pathologic pattern is usually nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP). Pulmonary vasculitis can cause pulmonary hypertension. RA-associated ILD is usually slowly progressive, however approximately 10% of patients die of progressive respiratory failure. Also, findings of ILD can be present before the onset of articular disease.

See Rheumatoid Arthritis for more information.

Scleroderma

The lungs are the second most common organ involved in scleroderma (SD), after the esophagus. SD (also referred to as progressive systemic sclerosis [PSS]) can be divided into 2 types: limited (CREST [calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome) and diffuse. ILD is more prevalent in diffuse SD (30-90%), and pulmonary hypertension is more common in limited SD (10%).

ILD in SD patients manifests as an insidious onset of dyspnea, hypoxia, and fatigue. Later, as the disease progresses, it becomes indistinguishable from IPF. It should be noted that ILD associated with SD follows a less progressive course than IPF does and has a better long-term prognosis.

Pulmonary hypertension (see the image below) is fatal in SD patients. It can occur alone or in combination with ILD. Dyspnea on exertion is the most common symptom, followed by syncope or right-sided chest pain.

Interstitial lung disease associated with collagen Interstitial lung disease associated with collagen-vascular disease. Pulmonary hypertension is a complication of various collagen-vascular diseases. This lung biopsy specimen demonstrates severe interstitial fibrosis and medial fibrosis, as well as smooth muscle hyperplasia of a pulmonary arteriole, features compatible with pulmonary hypertension.

Less commonly, SD can cause pleural disease, aspiration pneumonia, spontaneous pneumothorax, bronchiectasis, and drug-induced pulmonary toxicity (eg, methotrexate-mediated ILD).

See Scleroderma for more information.

Sjögren syndrome

Sjögren syndrome (SS) consists of the triad of keratoconjunctivitis sicca, xerostomia, and parotid swelling. It can be divided into 2 forms: primary (when other connective-tissue diseases are not present) and secondary (when other connective-tissue diseases are present). Pulmonary involvement (eg, pleuritis or vasculitis) is more common in secondary SS, and ILD is more common in primary SS.

Pleuropulmonary manifestations of SS include tracheobronchial gland inflammation, pleuritis, lymphoid interstitial pneumonia (LIP), NSIP, UIP, BOOP, and follicular bronchiolitis. Focal lymphoid hyperplasia (pseudolymphoma, a nonmalignant extraglandular lesion characterized by infiltrates of mature lymphocytes) and lymphoma (non-Hodgkin lymphoma) are more common in these patients.

See Sjogren Syndrome for more information.

Polymyositis/dermatomyositis

Polymyositis (PM)/dermatomyositis (DM) is less commonly associated with pulmonary lung disease. ILD occurs in 10% of patients with PM/DM. Patients with ILD tend to have shorter survival than patients without lung involvement. These patients present acutely with normal creatine kinase levels despite myositis. [51]

Infections are the most common form of pulmonary disease in PM/DM patients. Several mechanisms have been proposed, including weakness of the respiratory muscles, aspiration, lymphocytopenia, and immunosuppression from the drugs used to treat PM/DM.

See Polymyositis and Dermatomyositis for more information.

Mixed connective-tissue disease

Mixed connective-tissue disease (MCTD) is a rare autoimmune disorder that causes signs and symptoms of other connective-tissue diseases. Clinical and laboratory findings overlap those of PSS, SLE, and PM/DM. For this reason, MCTD is sometimes referred to as an overlap disease.

The lungs are commonly affected in persons with MCTD [52, 53] ; most patients are asymptomatic, but they may present with an insidious onset of dyspnea, dry cough, and chest pain. Pulmonary hypertension [54] is the most common cause of death in patients with MCTD.

See Mixed Connective-Tissue Disease for more information.

Ankylosing spondylitis

Ankylosing spondylitis (AS) involves the lungs in 1% of patients. Upper lobe and apical lung fibrosis is seen, usually 10 years or more after the onset of the disease. In 3.5% of cases, AS can cause aortic root dilation and aortic valve regurgitation.

See Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy for more information.

 

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Physical Examination

Physical examination is important in patients with CVDs. Physical findings may be limited to the chest or may involve other body organs (see the images and Table 1 below).

Interstitial lung disease associated with collagen Interstitial lung disease associated with collagen-vascular disease. Note the heliotrope rash in a woman with dermatomyositis.
Interstitial lung disease associated with collagen Interstitial lung disease associated with collagen-vascular disease. This image reveals Gottron papules and nail-fold telangiectasia in a patient with dermatomyositis.
Interstitial lung disease associated with collagen Interstitial lung disease associated with collagen-vascular disease. This image shows the classic malar rash (butterfly rash), with distribution over the cheeks and nasal bridge. Note that the fixed erythema (sometimes associated with mild induration, as seen here) characteristically spares the nasolabial folds.

Table 1. Important Physical Findings in Collagen-Vascular Diseases (Open Table in a new window)

CVD

Skin and Musculoskeletal System

Lungs

Heart

Salivary Glands

Eyes

RA*

Subcutaneous nodules, digital ulcers, nail-fold infarcts

Bibasilar Velcro crackles, signs of pulmonary hypertension, pleural effusion

Pericarditis, myocarditis

N/A

N/A

SLE*

Malar rash, alopecia, livedo reticularis, erythema, telangiectasia, capillary infarcts, polyarthritis

Pleural effusion or rub, pneumonitis, cor pulmonale, diaphragmatic weakness

Pericarditis, myocarditis, CAD

N/A

N/A

SD

Thickening of skin of face, fingers, and hands; Raynaud phenomenon and ischemic changes of fingertips

Cor pulmonale, inspiratory Velcro crackles at lung bases

Restrictive pericardial disease, conduction defects, CHF

N/A

N/A

SS*

Secondary SS can manifest similarly to RA and SLE

Secondary SS can manifest similarly to RA and SLE

N/A

Xerostomia, parotid gland swelling

Keratoconjunctivitis sicca

PM

Proximal muscle weakness

Respiratory muscle failure

N/A

N/A

N/A

DM

Heliotrope rash of eyelids, Gottron papules,

Respiratory muscle failure

N/A

N/A

N/A

AS

Sacroiliitis

Restriction in chest expansion, pulmonary apical fibrosis

Aortic insufficiency

N/A

Anterior uveitis

* MCTD can manifest with the signs and symptoms of RA, SLE, or SS.

AS = ankylosing spondylitis; CAD = coronary artery disease; CHF = congestive heart failure; CVD = collagen-vascular disease; DM = dermatomyositis; PM = polymyositis; RA = rheumatoid arthritis; SD = scleroderma; SLE = systemic lupus erythematosus; SS = Sjögren syndrome.

Interstitial pneumonia with autoimmune features (IPAF)

Specific clinical features suggestive of an underlying CTD are present but do not allow for the diagnosis of a defined CTD. For example, Raynaud's phenomenon, palmar telangiectasia, distal digital tip ulceration and digital edema are specific physical findings that are often seen in systemic sclerosis but rarely seen in idiopathic interstitial pneumonia (IIP). Similarly, the features of digital fissuring (“mechanic hands”) and a fixed rash on the digital extensor surfaces (Gottron's sign) are hallmarks of the anti-synthetase syndrome or systemic sclerosis-myositis overlap associated with PM-Scl antibody positivity. Inflammatory arthropathy is characterised by symptoms or signs of peripheral joint synovitis, but joint pain alone lacks specificity. [8]  

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