Typical features
Lymphadenopathy: hilar, mediastinal, bilateral symmetric, well defined
Nodules: micronodules (2- to 4-mm), well defined, larger coalescing nodules
Perilymphatic distribution: subpleural, interlobular septa, peribronchovascular
Fibrosis: reticular densities, architectural distortion, traction bronchiectasis, volume loss
Distribution: predominance of parenchymal abnormalities in upper lobes and perihilar areas
Atypical features
Lymphadenopathy: unilateral, isolated, in atypical mediastinal locations
Airspace consolidations: conglomerate masses, confluent alveolar opacities (alveolar sarcoidosis)
Linear opacities: interlobular septal thickening
Fibrocystic changes: cysts, bullae, honeycomb like opacities, upper lobe predominance
Airway involvement: atelectasis, mosaic pattern
Pleural disease: effusion, chylo/hemothorax, pneumothorax, pleural plaques
Especially in advanced disease stages with fibrosis, the differential diagnosis between sarcoidosis and other fibrosing diseases can be very challenging. Table 2 summarizes the imaging findings that are helpful in differentiating several diseases.
Table 2.
Diseases with imaging features that overlap with sarcoidosis
Differential diagnosis | Overlapping finding | Suggestive of sarcoidosis |
|---|---|---|
Lymphangitic carcinomatosis | • Irregular “beaded” thickening of the interlobular septa | • Upper lobe predominance |
• Absence of pleural effusion | ||
• Less central bronchial cuffing | ||
Silicosis/Pneumoconiosis | • Pleural pseudoplaques | • No calcifications in pseudoplaques |
• Eggshell calcifications of lymph nodes | • Pseudoplaques consist of confluent nodules | |
• Perinilar fibrotic masses | • The perihilar fibrotic masses extend directly from the hilar structures and move posteriorly (upper lobe volume loss) | |
• UIP pattern predominantly in upper lobes or perihilar region | ||
Chronic EAA/chronic HP and UIP/IPF | • Honeycombing | • Thickened interlobular septa |
• Traction bronchiectasis | • Lymph node calcifications | |
• Architectural distortion | • Fibrosis and traction bronchiectasis tend to run from the hilar structures dorsolaterally | |
• Lobular distribution of areas with air trapping (in the presence of obliterative bronchiolitis) and fibrosis | ||
Lymphoproliferative disorders | • Lymphadenopathy | • Usually but not always symmetric |
• Presence of typical parenchymal findings (caveat: biopsy may be necessary) | ||
Chronic beryllium disease | • Nodular pattern | • Large hilar lymphadenopathy |
• No exposure to beryllium | ||
• Other organ involvement | ||
Tuberculosis | • Nodular pattern (normally random versus perilymphatic nodules, however, sarcoidosis may occasionally show a random pattern) | • Egg shell or disperse calcifications as opposed to rough TB calcifications |
• Symmetric calcifications (in TB frequently asymmetric) | ||
• Clinical symptoms of acute infection in patients with miliary TB | ||
CVID | • Nodules in perilymphatic distribution | • Different clinical history (in CVID recurrent bacterial infection) |
• Ill-defined nodules in mid-lower predominance | • Different histological features |
Complications include the development of aspergillomas and pulmonary hypertension. Mycetomas are a typical complication of stage IV sarcoidosis: they present as a soft-tissue mass located in a preexisting cavitation in patients with fibrotic sarcoidosis. Life-threatening hemoptysis may require immediate interventional therapy (embolization of the bronchial arteries). Pulmonary hypertension occurs in patients with end-stage fibrosis but may be also caused by mediastinal fibrosis, extrinsic compression of the pulmonary arteries by lymphadenopathy, or intrinsic sarcoid vasculopathy, including features of pulmonary veno-occlusive disease.
Collagen Vascular Diseases
Collagen vascular diseases are characterized primary on clinical grounds, namely, typical clinical complaints and physical examination findings. The presence of specific autoantibodies may greatly assist in the correct diagnosis. Involvement of the respiratory system is often seen in collagen vascular diseases and results in significant morbidity and mortality. It is important to note that lung abnormalities may precede the other clinical manifestations, sometimes by more than 5 years.
Lung injury from collagen vascular disease can affect each portion of the lung, the pleura, alveoli, interstitium, vasculature, lymphatic tissue, and both the large and small airways. Commonly, more than one compartment is involved. Many of the parenchymal manifestations of collagen vascular disease are similar to those of the idiopathic interstitial pneumonias and can be classified using the same system.
Lung biopsy is rarely obtained in patients with a defined connective tissue disease. For this reason, HRCT often determines the predominant pattern of injury, which in turn is important in determining treatment and prognosis.
while many patterns of injury are associated with the particular collagen vascular diseases, certain patterns are more representative than others. For instance, nonspecific interstitial pneumonia is the most common pattern in patients with scleroderma. It is also important to note that more than one pattern of injury may be present in the same patient.
Rheumatoid Arthritis
Most patients with rheumatoid arthritis (RA) have abnormalities on HRCT. However, CT-detected abnormalities are often not associated with symptoms. Airways abnormalities such as bronchial wall thickening (12–92%) or bronchial dilation (30–40%) are more common than parenchymal changes, including reticular abnormality (10–20%), ground-glass opacity (15–25%), honeycombing (10%), and consolidation (5%). Nodular changes and pleural disease, the latter preceding parenchymal changes, are also seen.
Airways disease appears to be the earliest manifestation of RA in the lung. Bronchiectasis and air trapping are common findings. There is a recognized association between rheumatoid disease and obliterative bronchiolitis (constrictive bronchiolitis), in which the bronchioles are destroyed and replaced by scar tissue. The characteristic CT finding is mosaic perfusion with expiratory air trapping often associated with bronchial dilation. Follicular bronchiolitis is a second type of small-airway disorder recognized in rheumatoid lung disease. The major CT finding is centrilobular nodules and areas of ground glass opacity.
Rheumatoid lung fibrosis is substantially more common in males than in females. The two most frequently occurring patterns of lung fibrosis are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Of all connective tissue diseases, RA is the most common to present with a UIP pattern. The CT findings in interstitial pneumonia associated with RA are often indistinguishable from those of the idiopathic varieties; however, other findings, such as nodules, pulmonary arterial enlargement, or pleural abnormality, may provide a clue to the underlying diagnosis. UIP and NSIP both typically demonstrate a subpleural and basilar distribution of findings. A confident diagnosis of UIP may be made when honeycombing and reticulation is also present. In NSIP there is an absence of honeycombing and subpleural sparing is present.
The introduction of a new generation of biologic agents used to treat RA has resulted in a new array of potential pulmonary side effects. The most important of these is the impaired immunity related to the use of antitumor necrosis factor (TNF) antibodies (etanercept, infliximab, and adalimumab), which has resulted in a substantially increased incidence of tuberculosis (sometimes disseminated or extraarticular) and of nontuberculous mycobacterial infection.
Low-dose methotrexate may be associated with subacute hypersensitivity pneumonitis in 2–5% of patients. Pre-existing radiographic evidence of interstitial lung disease in patients with RA suggests a predisposition to the development of methotrexate pneumonitis. Infections, such as Pneumocystis pneumonia, are another potential complication of therapy.
Scleroderma (Progressive Systemic Sclerosis)
Parenchymal lung involvement is very common in patients with scleroderma. At autopsy, the lungs are abnormal in at least 80% of cases. Lung fibrosis is the most common pattern of abnormality, with NSIP being much more common (>90%) than UIP. Pulmonary hypertension, either isolated or in association with lung fibrosis, is another frequent finding. Pulmonary hypertension develops especially in patients with limited scleroderma (CREST syndrome). Esophageal dilation is seen on CT in up to 80% of cases.
The CT findings in scleroderma reflect the dominant NSIP histology. Cellular NSIP presents with ground glass opacity and/or a fine reticular pattern, often in posterior and subpleural distributions. Fibrotic NSIP shows irregular reticulation and traction bronchiectasis as the predominant findings. Honeycombing is often absent, but when present it is limited in extent. Cellular and fibrotic NSIP often co-exist such that the findings may overlap. Subpleural sparing is particularly suggestive of a NSIP pattern.
The lung fibrosis associated with scleroderma is associated with a much better prognosis than that found in idiopathic lung fibrosis, probably due in part to the predominant NSIP histology. Fibrotic changes may remain stable for many years. In a large treatment study, the extent of lung fibrosis identified on baseline CT was an important independent predictor of physiologic progression and of the response to treatment.
Pulmonary arterial hypertension usually causes enlargement of the main and proximal pulmonary arteries, as seen on chest radiograph or CT, but normal-sized pulmonary arteries do not exclude the diagnosis. The presence of pericardial thickening or fluid in patients with scleroderma is also a strong predictor of echocardiographic pulmonary hypertension.
There is an increased prevalence of lung cancer in patients with scleroderma, especially in those with lung fibrosis. The relative risk of malignancy ranges from 1.8 to 6.5.
Systemic Lupus Erythematosus
Pleuritis is the most commonly seen pleuropulmonary manifestation of systemic lupus erythematosus (SLE), found in 40–60% of patients, and may or may not be associated with pleural effusion.
Fibrotic interstitial lung disease is less frequent in SLE than in the other collagen vascular diseases. While pulmonary infection is said to be the most common pulmonary complication of lupus, acute pulmonary hemorrhage is also an important pulmonary complication of this condition, characterized radiologically by diffuse or patchy consolidation and ground glass abnormality.
In patients with lupus, acute lupus pneumonitis is a poorly defined entity, characterized by a variable degree of respiratory impairment accompanied by focal or diffuse pulmonary consolidation. It is now believed that most cases previously identified as lupus pneumonitis probably represented acute interstitial pneumonia with or without pulmonary hemorrhage. It is mostly associated with renal infiltration and multi-organ failure.
Other complications of lupus may include diaphragmatic dysfunction, pulmonary hypertension, and pulmonary thromboembolism, which may be related to the presence of antiphospholipid antibodies. Diaphragmatic dysfunction, thought to be due to a diaphragmatic myopathy, is manifested by reduced lung volumes (“shrinking lungs” with plate-like atelectasis).
Polymyositis/Dermatomyositis
The presence of interstitial lung disease (ILD) in polymyosistis/dermatomyositis (PM/DM) correlates strongly with the presence of anti-Jo-1 antibodies. Between 50% and 70% of patients who are anti-Jo-1 positive have ILD whereas the frequency of ILD falls to about 10% if antibodies are absent. ILD may antedate myositis in patients with anti-Jo-1 antibodies.
The most common pathological findings are NSIP and organizing pneumonia (OP), often occurring in combination. As with other collagen vascular diseases, the occurrence of interstitial pneumonia may precede the development of clinical myositis.
Lung disease associated with PM/DM or with the antisynthetase syndrome, a closely related entity, often has a typical CT appearance consisting of confluent ground glass opacity and consolidation in the lower lobes superimposed on a background of reticular abnormality with traction bronchiectasis. This pattern reflects the characteristic histologic combination of OP and fibrotic NSIP. On serial evaluation, the changes of consolidation, ground glass abnormality, reticular abnormality, and traction bronchiectasis may all be partially reversible with treatment. Consolidation may also progress to reticular abnormality.
PM/DM can be associated with other collagen vascular diseases (SLE, scleroderma, RA, Sjögren syndrome). There is an increased risk for malignancy (especially breast lung, ovary, and stomach malignancies), which in up to 20% of patients is concurrently diagnosed within 1 year of follow-up.
Sjögren Syndrome (SS)
CT provides substantial information regarding the patterns of pulmonary involvement by Sjögren syndrome (SS). These may be divided into airway abnormality, interstitial fibrosis, pulmonary hypertension, and those suggestive of lymphoid interstitial pneumonia.
Airway-related abnormalities consist of bronchial wall thickening, bronchiectasis, bronchiolectasis, and the tree-in-bud pattern. Small-airway disease may manifest as a mosaic attenuation pattern and expiratory air trapping.
NSIP and lymphoid interstitial pneumonia (LIP) are the most common patterns of parenchymal lung disease. NSIP resembles that seen in scleroderma. LIP is characterized by ground glass abnormality due to the homogeneous lymphocytic infiltration. Peribronchovascular, centrilobular, and subpleural nodules may also be seen, and cysts measuring 5–30 mm are often present. These cysts frequently contain thin septa; they may be associated with soft-tissue nodules sitting either close to them or in their walls. Similar cysts may be found in follicular bronchiolitis. These changes are ascribed to bronchiolar obstruction on the basis of lymphocytic wall infiltration. Cysts are helpful in distinguishing LIP from lymphoma.
Lymphoma should be suspected if consolidation, large nodules (>1 cm), mediastinal lymphadenopathy or effusions are present. However, similar large, “pseudo-alveolar,” poorly defined nodules were found in four patients with combined amyloidosis and LIP. In contrast to other cystic lung diseases, such as lymphangioleiomyomatosis, the cysts of LIP show a peribronchovascular and lower lung predominance.
Mixed Connective Tissue Disease
Mixed connective tissue disease (MCTD) is an overlap syndrome that is a distinct clinicopathological entity. The principal characteristics are the presence of: (1) features of SLE, scleroderma, and PM/DM, occurring together or evolving sequentially during observation; and (2) antibodies to an extractable nuclear antigen (RNP).
Pulmonary involvement is common in MCTD. A study of 144 unselected patients found CT evidence of infiltrative lung disease in 67%. Many affected patients are asymptomatic. The pulmonary abnormalities resemble those seen in SLE, SS, and PM/DM. Thus, pleural thickening and pleural and pericardial effusions are common. Ground glass attenuation is the most frequent parenchymal abnormality. The CT pattern corresponds most closely to that of NSIP. Less frequent findings include honeycombing, consolidation, and poorly defined centrilobular nodules.
Other important complications of MCTD are pulmonary arterial hypertension, and esophageal dysmotility, with sequelae of recurrent aspiration.
Undifferentiated Connective Tissue Disease (or Interstitial Lung Disease with Autoimmune Features)
Not all patients with interstitial lung disease meet the criteria of having a collagen vascular disease. Among patients with histologically proven UIP or NSIP whose disease was originally diagnosed as idiopathic, because it did not fulfill the criteria of one of the established collagen vascular diseases, subgroups of patients with one or more serological features of an autoimmune process have been subsequently identified. Several terms have been suggested to describe the condition detected in these subgroups, including undifferentiated connective tissue disease (UCTD), interstitial lung disease with autoimmune features, and lung-dominant CTD. Whether these patients have a better prognosis than patients without these autoimmune features or even a prognosis comparable to that of patients with established collagen vascular diseases is not yet known.
The term “lung-dominant CTD” has been proposed for the subgroup of patients with: (1) NSIP, UIP, LIP, OP, or diffuse alveolar damage in the lung determined by histology or HRCT; (2) insufficient extrathoracic features of a definite collagen vascular disease but a combination of serologic features suggesting an autoimmune process; and (3) no identifiable alternative cause for interstitial pneumonia.
Pulmonary Vasculitis/Diffuse Alveolar Hemorrhage
The pulmonary vasculitides encompass a clinically, radiologically, and histopathologically heterogeneous group of diseases that are usually associated with a systemic vasculitis. The clinical symptoms and radiologic signs suggestive of pulmonary vasculitis include diffuse alveolar hemorrhage (DAH), acute glomerulonephritis, upper-airways disease, lung or cavitary nodules, mononeuritis multiplex, and palpable purpura.
The classification of systemic vasculitis remains controversial. In the most recent classification, the Chapel Hill Consensus Conference (CHCC) of 2012 (Table 3), the main consideration remained the predominant vascular size involved but the presence of ANCA (anti-neutrophil cytoplasmic antibody) was newly added. Small vessel vasculitis (SW) is divided into ANCA-associated vasculitis (AAV) and immune complex SW AAV represents necrotizing vasculitis with only few or no immune deposits predominantly affecting the small vessels; patients are MPO-ANCA or PR3 ANCA positive but in a minority of cases ANCA-negative. ANCA specificity should be indicated because it appears to identify distinct categories of disease.
Table 3.
The most recent classification of systemic vasculitis: from the 2012 Chapel Hill Consensus conference
Vasculitis | Pulmonary-renal syndrome | Pulmonary hemorrhage | Pulmonary hypertension | |
|---|---|---|---|---|
Small-vessel vasculitis, ANCA-associated | GPA | Pulmonary involvement 90% | In about 10% | – |
(formerly Wegener’s) | Renal involvement 80% | |||
Eosinophilic granulomatous | up to 25% | Rare | – | |
vasculitis with polyangiitis | ||||
GPA(Church Strauss)
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|