Hospital Medicine

Interstitial lung disease

Rheumatologic interstitial lung disease

I. Problem/Condition.

The interstitial lung diseases (ILDs) are a group of diffuse parenchymal lung disorders that are classified according to their specific clinical, radiological, and histopathological features. Table I below shows a simple classification according to etiologies. ILD can complicate many rheumatological or connective tissue disorders (CTDs), and occurs with higher frequency in certain conditions than in others. Scleroderma frequently has pulmonary involvement, whereas rheumatoid arthritis, lupus, inflammatory myositis (polymyositis and dermatomyositis), Sjogren’s, and mixed connective tissue disorder can less frequently be associated with ILD. Many CTDs can also be associated with disorders of the pleura, airways, and pulmonary vasculature as well, but this section will discuss parenchymal lung disease or ILD.

Table I.

Classifications of interstitial lung diseases

The pathophysiology of CTD-associated ILD is related to autoimmune-associated inflammation and fibrosis. Several histopathological patterns are seen, including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), diffuse alveolar damage (DAD), and lymphocytic interstitial pneumonia (LIP).

II. Diagnostic Approach

A. What are the symptoms of ILD in patient with CTD?

Patients with CTD and ILD complain of dyspnea with minimal exertion, cough (mainly dry), and other nonspecific symptoms including fevers, fatigue and weight loss.

What is the differential diagnosis for this problem?

Pulmonary symptoms in a patient with CTD can have several causes other than ILD.

  • Pleural effusions, pleuritis, pulmonary hypertension can be associated with ILD

  • Volume overload from cardiac or renal failure

  • Pulmonary embolism due to the hypercoagulable state of chronic inflammation

  • Pulmonary infection from immunosuppressive therapy

  • Side effects of drugs used to treat CTD (e.g., methotrexate)

It is worth noting that ILD may sometimes be the presenting manifestation of CTD. These patients have serological markers for CTD but joint, skin, or other organ involvement appears months or even years later after the onset of ILD. This is referred to as Interstitial Pneumonitis with Autoimmune Features (IPAF) or lung-dominant CTD.

B. Describe a diagnostic approach/method to the patient with this problem

Patients with CTD who develop pulmonary symptoms should undergo testing to assess the severity of their disease (pulse oximetry, pulmonary function tests [PFTs]) as well as tests to determine the etiology. Infection should be ruled out in patients on immunosuppressant medications.

1. Historical information important in the diagnosis of this problem.

In addition to knowing which CTD the patient has been diagnosed with, it is also important to know the antibody profile associated with their disease. The presence of certain antibodies influences the type, prevalence, and severity of ILD. For example, systemic sclerosis associated with Scl-70 antibodies is more likely to be associated with ILD/pulmonary fibrosis whereas the CREST syndrome, associated with anti-centromere antibodies, is most likely to be associated with pulmonary arterial hypertension. The presence of anti-Jo-1 in patients with inflammatory myositis syndromes (poly and dermatomyositis) significantly increases the likelihood of ILD.

Other important information includes:

  • Did symptoms begin suddenly or gradually?

  • Any exposures to dusts, chemicals or pets?

  • Is the patient taking any medications known to cause pulmonary disease (e.g. methotrexate, amiodarone)?

  • Are there any signs of cardiac or renal failure?

  • Does the patient have chronic aspiration?

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

  • Look for extrapulmonary evidence of a systemic disease including joint deformities, skin tightness, telangiectasia, petechial hemorrhages, rash and mechanical hands signs of CTD.

  • Lung auscultation is variable and often reveals coarse ("dry" or "velcro") crackles

  • Jugular venous distension, lower extremity edema and right-sided heart failure indicate severe disease with right-sided heart failure

  • Look for cyanosis and clubbing

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

All patients with ILD should have CTD biomarkers checked. These will aid in the diagnosis and has implications in treatment and prognosis of CTD-ILD (See Table II).

Table II.

Serologic testing in Connective tissue disease

Chest radiograph and PFTs with lung volumes and carbon monoxide diffusing capacity (DLCO) measurement should also be obtained. Patients with suspicion of ILD based on these tests should undergo high resolution computed tomography (HRCT). If certain characteristic findings on HRCT imaging are present in patients with an appropriate clinical history, a diagnosis of CTD-ILD can be made and no further work up to aid diagnosis is required.

In patients with less typical findings, a surgical or video-assisted lung biopsy (VAT) is often required to confirm the diagnosis. Table III shows the radiologic/clinical diagnosis with corresponding histopathological diagnosis.

Bronchoscopy should not be performed for purpose of diagnosing CTD-ILD. The bronchoscopy-guided transbronchial biopsy specimens are often inadequate for the diagnosis of ILD. However, bronchoscopy with bronchial alveolar lavage (BAL) may be performed to exclude infections.

Table III.

Clinical Diagnosis and Corresponding Histopathological diagnosis

C. Characteristic findings of specific tests in CTD-ILD

  • PFT shows restrictive ventilatory impairment with decreased diffusion capacity.

  • Characteristic pattern on HRCT includes basilar ground-glass opacities and septal thickening in NSIP, peripheral and basilar reticulonodular opacities and honeycombing in UIP, patchy airspace consolidation in COP, or cysts with centrilobular nodules and ground-glass opacities in LIP seen in Sjorgen’s disease.

  • Surgical lung biopsy demonstrating characteristic histologic pattern which correlates with the HRCT findings of NSIP, UIP, COP or LIP.

The process of reaching the final diagnosis, therefore, requires a multidisciplinary approach and discussion among the treating clinician, radiologist and the surgeon obtaining the biopsy.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

If clinical and radiographic findings are characteristic, the diagnosis of CTD-ILD can be made without surgical lung biopsy.

III. Management while the Diagnostic Process is Proceeding

A. Management of rheumatologic interstitial lung disease.

Patients with CTD-ILD most often present with insidious onset and gradual progression of dyspnea. Acute respiratory failure is more common in lupus, as patients can develop acute interstitial pneumonia (AIP) or diffuse alveolar hemorrhage (DAH). These patients may require admission in an intensive care unit, as well as treatment with lupus specific medications.

In any disease, hypoxia and signs of right ventricular failure should be addressed immediately. This may be a sign of CTD-associated pulmonary arterial hypertension (CTD-PAH).

The mainstay of therapy for CTD-ILD is treatment of the underlying CTD, with considerations for immunosuppressive therapy as follows.

  • Corticosteroids: Medium- to low-dose therapy with prednisone is used. High-dose steroids in scleroderma should be avoided because of concern of precipitating scleroderma renal crisis.

  • Cytotoxic drugs: Cyclophosphamide is the most commonly used agent. Azathioprine and mycophenolate are alternatives when cyclophosphamide toxicities are intolerable.

  • Lung transplantation is an option for patients with rapidly progressive lung disease. Particular attention is paid to esophageal involvement before lung transplant. Gastroesophageal reflux disease caused by esophageal dysmotility can lead to allograft dysfunction.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

  • Use supplemental oxygen as needed, unless drug-induced (e.g., amiodarone) pneumonitis is suspected, as oxygen will worsen the disease.

  • Avoid aggressive diuresis in patients with right ventricular failure, as they are preload- dependent.

  • Non-invasive positive pressure ventilation should be considered early in the absence of contraindications.

  • All patients should receive chemical deep vein thrombosis (DVT) prophylaxis in the absence of contraindications.

  • All patients should be prescribed aggressive pulmonary expansion therapy (e.g., incentive spirometry) to avoid complications due to atelectasis.

What’s the Evidence?/References

Solomon, JJ, Chartrand, S, Fischer, A. "Current approach to connective tissue disease-associated interstitial lung disease". Curr Opin Pulm Med. vol. 20. 2014 Sep. pp. 449-56.

Vij, R, Strek, ME. "Diagnosis and treatment of connective tissue disease-associated interstitial lung disease". Chest. vol. 143. 2013 Mar. pp. 814-24.

Fischer, A, du Bois, R. "Interstitial lung disease in connective tissue disorders". Lancet. vol. 380. 2012. pp. 689-98.

Ruano, CA, Lucas, RN, Leal, CI, Lourenço, J, Pinheiro, S, Fernandes, O, Figueiredo, L. "Thoracic Manifestations of Connective Tissue Diseases". Curr Probl Diagn Radiol. vol. 44. 2015 Jan-Feb. pp. 47-59.

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