Idiopathic pulmonary fibrosis

A 70-year-old man is evaluated in the office for dyspnea on exertion. He reports feeling well until about 8 months ago, when he developed slowly progressive shortness of breath. He also developed an intermittent dry cough. He does not have chest pain, fever, or chills. He has no other medical problems, has never smoked cigarettes, and takes no medications other than an occasional aspirin. He is a retired professor and has never worked outside of academia. His hobbies include golf and fishing.

On physical examination, the patient is dyspneic at rest and has digital clubbing. Temperature is 37 °C (98.6 °F), blood pressure is 130/82 mm Hg, heart rate is 90/min, respiration rate is 16/min, and oxygen saturation is 88% with the patient breathing room air. Pulmonary auscultation reveals bilateral basilar end- inspiratory Velcro-like crackles. Cardiac examination is normal.

Routine serologic studies and urinalysis are normal. Chest radiograph shows diffuse, predominantly basilar bilateral infiltrates.

Which of the following is the most likely diagnosis?
A Asbestosis
B Chronic obstructive pulmonary disease
C Cryptogenic organizing pneumonia
D Idiopathic pulmonary fibrosis
E Sarcoidosis



Key Points

* Idiopathic pulmonary fibrosis is characterized by basilar-predominant infiltrates on chest radiography, restrictive lung physiology, and evidence of impaired gas exchange.
* Physical examination clues compatible with idiopathic pulmonary fibrosis include digital clubbing and bibasilar end-inspiratory crackles with a Velcro-like quality.

Answer and Critique (Correct Answer = D)


This patient most likely has idiopathic pulmonary fibrosis, which is a specific form of chronic fibrosing interstitial pneumonia of unknown cause limited to the lung. It is characterized by predominantly basilar infiltrates on chest radiograph, restrictive physiology, and evidence of impaired gas exchange. Most patients with this disorder are more than 50 years old and develop progressive dyspnea and nonproductive cough, with many patients reporting symptoms of more than 6 months' duration before medical evaluation. Fever is rare, and when present, suggests an alternative diagnosis. Weight loss, fatigue, and malaise may be present. More than 80% of patients have bibasilar end-inspiratory dry crackles that have a Velcro-like quality. Cardiac examination may be normal or, in the case of advanced disease, show evidence of cor pulmonale. Digital clubbing occurs in 25% to 50% of patients. The next diagnostic steps in this patient include chest CT to evaluate the type of infiltrate and complete pulmonary function testing to confirm the presence of restrictive pulmonary disease with evidence of impaired gas exchange. Lung biopsy is often needed to establish the diagnosis.

Asbestosis is the best characterized of the occupational lung diseases and may present similarly to pulmonary fibrosis. Although asbestosis typically involves the lung bases, it is unlikely in the absence of an exposure history. On high-resolution CT scan, more than 90% of patients with asbestosis show some pleural abnormality such as pleural plaques or thickening. Chronic obstructive pulmonary disease is unlikely in a nonsmoker and in the absence of other irritant exposures. Additionally, this patient's chest radiograph is not consistent with chronic obstructive pulmonary disease, which typically includes hyperinflation, flattened diaphragms, and increased anterior-posterior diameter. Cryptogenic organizing pneumonia is characterized by a preceding flu-like illness in 40% of patients, with most patients reporting fewer than 3 months of symptoms before medical evaluation. This disorder may be associated with collagen vascular diseases, neoplasms, and viral illnesses. Chest radiograph may show unilateral or bilateral consolidation, with nodules in 10% to 50% of patients. High-resolution CT scan shows patchy air space consolidation in the periphery of the lung and often in the lower lung zones. This disorder often presents like a community-acquired pneumonia and is not compatible with this patient's slowly progressive disease. Sarcoidosis typically presents with bilateral hilar lymphadenopathy with or without infiltrates and may include extrapulmonary manifestations such as liver involvement, uveitis, or arthritis. High-resolution CT scan may show nodules along bronchovascular bundles with bilateral hilar and mediastinal lymphadenopathy.
Bibliography

1. Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, Brown KK; IPF Study Group. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005:21;142:963-7. Summary for patients in: Ann Intern Med. 2005;142:I23. [PMID: 15968010] [PubMed]

CREST syndrome

A 48-year-old man is evaluated in the office for progressive exertional dyspnea and a nonproductive cough. He is an ex-smoker (30-pack-years) and has gastroesophageal reflux disease, hypertension, and hypothyroidism. His medications are a proton pump inhibitor, an angiotensin-converting enzyme inhibitor, and thyroid hormone replacement.

On physical examination, blood pressure is 140/88 mm Hg, heart rate is 86/min, and respiration rate is 16/min. The skin on the hand is shown (Figure 27). He has localized areas of skin thickening on the arms and chest. Bibasilar mid- to late-inspiratory crackles are audible. There is no peripheral edema.

High-resolution CT scan of the chest shows reticular lines that are most prominent in the periphery of the lower lobes, accompanied by patchy, ground-glass opacities. Pulmonary function testing shows an FEV1 84% of predicted, an FVC 78% of predicted, and a DLCO 39% of predicted. Antinuclear antibody titer is 1:160.

Which of the following is the most likely diagnosis?
A Hypersensitivity pneumonitis
B Idiopathic pulmonary fibrosis
C Systemic sclerosis (scleroderma)
D Systemic lupus erythematosus


Key Points

* Lung disease is the most common cause of morbidity and mortality in patients with systemic sclerosis (scleroderma).
* In systemic sclerosis, both interstitial lung disease and pulmonary hypertension can develop (independently or together) and have an adverse effect on outcome.

Answer and Critique (Correct Answer = C)

In patients with systemic sclerosis (scleroderma), the lung is commonly involved, and lung disease is now the most common cause of scleroderma-related morbidity and mortality. Scleroderma is suggested by the typical skin findings. Pigment changes appear first, followed by skin thickening, digital pitting, and ulceration. Skin changes can extend proximally; patients with skin findings proximal to the elbows have diffuse scleroderma, as does this patient. In patients with scleroderma, both interstitial lung disease and pulmonary hypertension can develop (either independently or together) and have an adverse impact on outcome. Pulmonary disease can also be the initial clinical manifestation of scleroderma and is most commonly associated with diffuse scleroderma. Pulmonary hypertension is more commonly associated with limited scleroderma (CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia). A comprehensive history and physical examination are necessary to identify and confirm the underlying cause. In this patient, the presence of gastroesophageal reflux disease, sclerodactyly, proximal skin findings, late crackles on examination, abnormal high-resolution CT scan findings, a restrictive pulmonary physiologic defect, and the positive antinuclear antibody titer suggest the presence of scleroderma-related interstitial lung disease.

Idiopathic pulmonary fibrosis is an idiopathic interstitial pneumonia (i.e., it occurs in the absence of other explanations for the lung disease). The presence of features suggestive of scleroderma excludes this diagnosis. Various intrathoracic complications occur in patients with systemic lupus erythematosus; however, classic interstitial lung disease is uncommon. The clinical diagnosis of hypersensitivity pneumonitis requires a specific exposure that is temporally related to the development of the lung disease, and the high- resolution CT scan pattern is generally one of centrilobular nodules with areas of focal air-trapping. In addition, hypersensitivity pneumonitis cannot explain the patient's skin findings and gastroesophageal reflux disease.
Bibliography

1. Steen VD. The lung in systemic sclerosis. J Clin Rheumatol. 2005;11:40-6. [PMID: 16357695] [PubMed]