The Core Curriculum: Cardiopulmonary Imaging, 1st Edition (2004)

Chapter 13. Pulmonary Manifestations of Systemic Diseases

Many systemic diseases have thoracic manifestations. In some patients the initial presentation of the disease can be abnormality on chest x-ray (CXR) or chest computed tomography (CT). Only some of the more common diseases are covered in this chapter.

Collagen Vascular Disease

Rheumatoid Arthritis

Rheumatoid arthritis is usually insidious in onset, marked by ill health and chronic joint deformity. It has a prevalence of up to 2%, an age at onset of 25 to 55 years, and a male-to-female ratio of 1:3. Rheumatoid factor is positive in 50% to 70% of patients. The term “rheumatoid disease” may be more appropriate. Although the brunt of disease falls on the joints, this is a systemic connective tissue disease with extraarticular manifestations (pulmonary, cardiac, vascular, reticuloendothelial, hematologic, renal, and ocular) in up to 76% of patients (1,2,3,4,5,6,7). Rheumatoid lung disease affects 2% to 54% of patients with rheumatoid arthritis, with a male-to-female ratio of 5:1. The manifestations may be subdivided into eight categories (Table 13.1.).

Although rheumatoid disease has a 3:1 female predilection, rheumatoid lung disease has a 5:1 male-to-female ratio.

Pleural abnormalities are most frequent (Fig. 13.1A), manifesting as unilateral exudative pleural effusion in 90% of patients and sometimes demonstrating little change over months. Bilateral large effusions can be seen. For pleural disease, the male-to-female ratio is 9:1 (5). There are usually not other pulmonary rheumatoid changes. Pleural disease may antedate the onset of arthritis. The effusion is an exudate with protein content greater than 4 g/dL, a low glucose content (less than 30 mg/dL), and no rise in pleural glucose during intravenous glucose infusion (as opposed to tuberculosis, which also has low pleural fluid glucose). There is generally a low white cell count with many lymphocytes, and pleural fluid is usually positive for rheumatoid factor, lactate dehydrogenase, and rheumatoid arthritis cells (8). Pleural thickening may also occur, usually bilaterally. Pleural fibrosis and adhesions are often found at autopsy. Pneumothorax can occur secondary to rupture of a rheumatoid nodule or end-stage fibrotic lung disease.

Table 13.1: Radiologic Manifestations of Rheumatoid Arthritis

Pleural abnormalities
Diffuse interstitial fibrosis
Necrobiotic nodules
Caplan syndrome
Bronchial abnormalities
Pulmonary arteritis
Cardiac enlargement
Bone abnormalities on chest radiograph

Diffuse interstitial fibrosis is seen in 2% to 6% (8), most frequently with seropositive rheumatoid arthritis. It causes a restrictive ventilatory defect with deposition of IgM in alveolar septa and has a lower lobe predominance. The radiographic findings are often indistinguishable from idiopathic pulmonary fibrosis or usual interstitial pneumonitis (Fig. 13.1B). Irregular linear opacities, honeycombing, or a reticulonodular pattern are seen in the lower lobes and occasionally more cephalad. High resolution CT (HRCT) has greatly improved early detection of fibrosis with inter- and intralobular septal thickening and patchy ground glass opacity, mainly in a subpleural distribution. As disease progresses, it eventually results in honeycombing. It is thought that rheumatoid lung disease is more benign than usual interstitial pneumonitis (7,8,9).

Necrobiotic nodules are identical to subcutaneous nodules. They are well-circumscribed masses in the lungs, pericardium, and visceral organs and are associated with advanced rheumatoid disease. They are a rare manifestation in the lungs. They are usually multiple and noncalcified, measuring 3 mm to 7 cm in size. They are commonly located in the lung periphery. Nodules may cavitate, typically with a thick wall and a smooth outline. They are often found in conjunction with subcutaneous nodules that wax and wane with the activity of the disease (1,3,7,8,9).

Caplan syndrome consists of multiple nodules due to hypersensitivity reaction to irritating coal dust particles in the lungs of coal miners with rheumatoid. Appearances are similar to necrobiotic nodules without pneumoconiosis. These well-defined nodules of 5 mm to 5 cm may develop rapidly. They tend to appear in clusters, predominantly in the upper lobes and in the lung periphery. Nodules may remain stable but may increase in number, may calcify, or may resolve completely. There is no relationship between severity of arthritis and extent of nodules.

Figure 13.1 Rheumatoid disease. A. Computed tomography: moderate loculated right pleural effusion (E). B. High resolution computed tomography photographed at lung window settings, more caudal than A: peripheral basilar fibrotic change, with traction bronchiectasis(arrows) and honeycombing (arrowheads).

Bronchial abnormalities such as bronchiectasis or bronchiolitis obliterans occasionally occur. Pulmonary arteritis is a rare manifestation of rheumatoid arthritis, with fibroelastoid intimal proliferation of the pulmonary arteries that may result in pulmonary arterial hypertension and/or cor pulmonale (8). Cardiopericardial silhouette enlargement is also unusual and may result from pericarditis with pericardial effusion or myocarditis causing congestive cardiac failure.

Various bone abnormalities may be seen on the CXR. This includes arthritis of visualized joints, ankylosis of vertebral facet joints, and vertebral body collapse secondary to steroid therapy.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) has an incidence of 1 in 2,000, a typical age at onset between 20 and 40 years, and is nine times more common in females than males. It is common in the United States and East Asia, and the incidence is greater in African Americans. Among African-American women the incidence approaches 1 in 250, and disease often has a more severe course. There is an increased incidence of the human leukocyte antigens (HLAs) B8 and DR3. SLE may be exacerbated by sunlight and infection, and a lupus-like syndrome is induced by certain drugs such as hydralazine, oral contraceptives, phenothiazines, and procainamide. The most common early features are fever, arthralgia, general ill health, and weight loss. A characteristic manifestation is the “butterfly” rash on the face, although this does not have to be present. Antinuclear antibodies are present in 95%. The presence of antibodies to double-stranded DNA is diagnostic, although Sm antibodies are more specific for SLE. Hypergammaglobulinemia occurs in 77%, lupus erythematosus (LE) cells in 80%, and a false-positive Wasserman test for syphilis in 24%. SLE affects the joints in 90% of patients, the skin in 80%, the kidneys in 60%, the lungs in 50% to 70%, the cardiovascular system in 40%, the nervous system in 35%, and also the blood and lymphatic system (1,2,5,6,7). SLE affects the respiratory system more commonly than any other connective tissue disease, with radiologic abnormalities listed in Table 13.2.

SLE affects the respiratory system more commonly than any other connective tissue disease.

Radiographically, the acute form (lupus pneumonitis) is characterized by poorly defined areas of ground glass opacity or consolidation peripherally at the lung bases. In the chronic form there is basal interstitial pulmonary fibrosis, seen in approximately 3% of patients (Fig. 13.2) (5). Bibasal fleeting plate-like atelectasis secondary to infection or infarction can also occur. Alveolar hemorrhage may manifest as ground glass opacity or consolidation. Patients with SLE have an increased incidence of pulmonary emboli secondary to circulating antiphospholipid antibodies. Pulmonary infections due to immunosuppressive therapy are also seen (10,11).

Table 13.2: Radiologic Manifestations of SLE

Pulmonary abnormalities
   Ground glass opacity (pneumonitis or hemorrhage)
   Consolidation (pneumonitis or hemorrhage)
   Atelectasis
   Pulmonary embolism
Pleural abnormalities
   Effusion (pleuritis)
   Thickening
Cardiovascular abnormalities
   Effusion (pericarditis)
   Cardiomegaly (cardiomyopathy)

SLE, systemic lupus erythematosus

Pleural effusion is the most common radiographic manifestation (Fig. 13.3), with recurrent small bilateral pleural effusions in 70%. Pleural thickening may also occur. Pericardial effusion from pericarditis is also common. Cardiomegaly from primary lupus cardiomyopathy is a rare manifestation (10,11).

Figure 13.2 Systemic lupus erythematosus. High resolution computed tomography with basilar fibrotic disease, worst in the left lung(arrows).

Figure 13.3 Systemic lupus erythematosus, with left pleural effusion (E).

Progressive Systemic Sclerosis or Scleroderma

Scleroderma has an incidence of 2 to 12 per million, a typical age at onset of less than 45 years, and a male-to-female ratio of 1:3. It is a systemic disease with atrophy and sclerosis of the skin, gastrointestinal tract, musculoskeletal system, lungs, and heart. There is an association with primary biliary cirrhosis. Blood vessels show arteritis and thickening. Generally, the clinical presentation includes fever, lassitude, and weight loss. Antinuclear antibodies are present in 30% to 80%. Anti-topoisomerase or antiScl-70 is present with diffuse cutaneous involvement; anti-centromere antibody is present in one-third of patients with progressive systemic sclerosis and in two-thirds of patients with a more limited form of the disease known as CREST (calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, andtelangiectasias). Progressive systemic sclerosis affects the skin in 90% of patients; the vascular system, esophagus, and intestines in 80%; the lungs in 45%; the heart in 40%; the kidneys in 35%; and the musculoskeletal system in 25% (1,2,7,12).

Basilar interstitial pneumonitis and fibrosis is the usual CXR abnormality, present in up to 80% (3) of patients with lung disease. The basilar distribution is even more pronounced in progressive systemic sclerosis than in other collagen vascular diseases. On CXR there may be fine or coarse reticulations at the bases with low lung volumes. HRCT demonstrates inter- and intralobular septal thickening, subpleural lines and micronodules, ground glass opacity, and honeycombing (Fig. 13.4). Aspiration pneumonia may occur secondary to disturbed esophageal motility. Esophageal dysmotility may result in a dilated air esophagram on CXR or CT. Pleural involvement is rare. Pulmonary arterial hypertension occurs in 6% to 60% (13), and sclerosis of cardiac muscle may result in cor pulmonale. There is an increased risk of lung cancer, especially bronchoalveolar carcinoma.

Basilar distribution of lung disease, typical of most collagen vascular diseases, is especially pronounced in scleroderma.

Polymyositis and Dermatomyositis

These diseases have an incidence of 1 to 8 per million, a bimodal age distribution with an early peak at 5 to 15 years and a later peak at 45 to 65 years, and male-to-female ratio of 1:4. There is an increased incidence of HLAs A1, B8, DR3, and DR5. Clinical presentation may be acute or chronic, with proximal muscle weakness, a heliotrope or violaceous skin rash in dermatomyositis, and telangiectasias over the joints of the hand. Dysphagia occurs in up to 50%. Skin and muscle changes may occur together or 2 to 3 months apart. General ill health and fever are common. Disease is associated with the anti-Jo1 antibody. In 10% there is an underlying malignancy, with carcinomas of lung, breast, stomach, and ovary being the most common. In men presenting over the age of 50, 60% have carcinoma, usually bronchogenic carcinoma (1,2,5). Polymyositis/dermatomyositis presents in one of four ways:

1. Primary idiopathic polymyositis/dermatomyositis;

2. Childhood polymyositis/dermatomyositis;

3. Polymyositis/dermatomyositis with neoplasia;

4. Polymyositis/dermatomyositis with collagen vascular disease.

In 10% of polymyositis patients there is an underlying malignancy, often in lung, breast, stomach, or ovary.

Figure 13.4 Scleroderma. High resolution computed tomography with interstitial abnormality limited to the lung bases. Note esophageal dilation (E).

Chest radiographs are often normal. Basal interstitial pulmonary fibrosis indistinguishable from usual interstitial pneumonitis or nonspecific interstitial pneumonitis occurs in up to 10% (Figs. 13.5 and 13.6). Bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia also occur. When pharyngeal muscle paralysis occurs in polymyositis, aspiration pneumonia may develop. Diaphragmatic elevation with small lung volumes can also be seen (3,7,14).

Figure 13.5 Dermatomyositis. High resolution computed tomography demonstrates extensive ground glass opacity with traction bronchiectasis (arrows).

Figure 13.6 Dermatomyositis. High resolution computed tomography predominantly with traction bronchiectasis at the extreme lung bases.

Ankylosing Spondylitis

Of all the seronegative arthritides, ankylosing spondylitis is the main one with chest manifestations. It has an incidence of 1 in 1,000, an age at onset of 15 to 35 years, and male-to-female ratio of 4:1. It is most common in people from the Indian subcontinent. It is more common in whites than blacks and is rare in East Asians. There is a 90% association with HLA B27 (1,2,5). Characteristic findings include synovitis, juxtaarticular osteitis and chondritis with erosion of subchondral bone, and skeletal ankylosis, especially of the sacroiliac joints. Calcification of paraspinal ligaments is noted if there is involvement of the lumbar, thoracic, or cervical spine. Aortic regurgitation is seen in up to 5% of patients. In 1% to 2% of patients, upper lobe pulmonary fibrosis and bullae develop. These fibrobullous lesions may contain mycetomas and are occasionally secondarily infected by Mycobacterium tuberculosis (3,7,15).

Unlike other collagen vascular diseases, lung disease in ankylosing spondylitis has an upper lobe predilection.

Pulmonary Vasculitides

The pulmonary vasculitides can be categorized according to the size of the vessels primarily involved (Table 13.3) and to whether they are associated with an elevated antinuclear cytoplasmic antibody (ANCA). These disorders have manifestations in many other organ systems, commonly the skin and kidneys, and frequently present with pulmonary hemorrhage (3).

Non–Antinuclear Cytoplasmic Antibody Associated Vasculitides

Large Vessel (Giant Cell) Vasculitis

Giant cells are a prominent histologic feature of both giant cell (temporal) and Takayasu arteritis. The aorta and great vessels are usually affected, and CT may demonstrate vascular narrowing. Other chest manifestations are extremely rare (1,2,16,17).

Medium-sized Vessel Vasculitis

In polyarteritis nodosa, pulmonary artery involvement is rare, whereas bronchial artery involvement is common. However, thoracic radiologic findings are usually secondary to cardiac and/or renal failure. A few cases of idiopathic pulmonary fibrosis and cryptogenic organizing pneumonia have been described (1,2,17).

Table 13.3: Principle Systemic Vasculitides

Large vessel vasculitides
   Giant cell (temporal) arteritis
   Takayasu arteritis
Medium-sized vessel arteritis
   Polyarteritis nodosa
   Kawasaki disease
Small vessel vasculitis
   ANCA associated (pauci-immune, lacking immune complex)
      Microscopic polyangiitis
      Wegener granulomatosis
      Churg-Strauss syndrome
   Immune complex vasculitis
      Henoch-Schonlein purpura
      Mixed cryoglobulinemia
      Connective tissue disorders
      Hypocomplementemic urticarial vasculitis
      Behçet disease
      Goodpasture syndrome
      Serum sickness/drug/infection

ANCA, Antinuclear cytoplasmic antibody.

Antinuclear Cytoplasmic Antibody Associated Vasculitides

Microscopic Polyangiitis

Microscopic polyangiitis is pauci-immune necrotizing small vessel angiitis without granulomatous inflammation. It is a rare disease, has a mean age at onset of 50 years, and a male-to-female ratio of 2:1. It presents with constitutional symptoms, including fever, arthralgias, myalgias, and purpura. pANCA is present in more than 80% of patients. It is the most common cause of a pulmonary–renal syndrome. Common radiologic findings in the chest are pulmonary edema in 6% of patients and pleural effusion in 15% (1,2,3,16).

Wegener Granulomatosis

Classic Wegener granulomatosis is a triad of (a) upper and lower respiratory tract necrotizing granulomatous inflammation, (b) systemic small vessel vasculitis, and (c) necrotizing glomerulonephritis. It has an incidence of 3 per million, a mean age at onset of 40 years, and a male-to-female ratio of 1.3:1. There is an increased incidence of HLAs B8 and DR2. Onset is usually acute or subacute but may be indolent. In patients with Wegener granulomatosis, 85% have a positive cANCA (1,2,3).

The upper respiratory tract is involved in 100% of cases, affecting the nasal cavity with cartilage destruction and the sinuses with mucosal thickening. Pulmonary involvement is present in 85% to 90% (5). The classic CXR shows widely distributed multiple irregular nodules or masses, varying up to 9 cm, mainly in the lower lungs. Nodules cavitate in 25% to 50% of patients (Fig. 13.7) and are sometimes single. Patchy airspace disease due to pneumonia or pulmonary hemorrhage also occurs (Fig. 13.8). Pleural effusions occur in 25% and tracheobronchial stenosis is not uncommon (Fig. 13.9), but lymph node enlargement is rare. Limited Wegener granulomatosis is Wegener granulomatosis without the renal involvement (3,16,17,18).

Common thoracic manifestations of Wegener granulomatosis are lung nodules or cavities, pulmonary hemorrhage, pleural effusions, and tracheobronchial stenosis.

Figure 13.7 Wegener granulomatosis. Computed tomography reveals large bilateral cavitary masses (M).

Churg-Strauss Syndrome

This consists of a triad of (a) allergic rhinitis and asthma, (b) eosinophilic pneumonia and gastroenteritis, and (c) systemic small vessel vasculitis with granulomatous inflammation. The disease often evolves in this order. It is rare, has a typical age at onset of 38 to 57 years, and affects men and women equally. pANCA is elevated in 70%, cANCA is rarely elevated, tissue eosinophilia occurs in 100% with serum eosinophilia in greater than 30%, and serum IgE is commonly elevated. The cardiac, gastrointestinal, skin, and central nervous systems are commonly involved (1,2,3,5). CXR manifestations include patchy airspace disease, noncavitary pulmonary nodules, and pleural effusions. Cardiopericardial silhouette enlargement results from pericarditis and/or myocarditis (16,17,19).

Figure 13.8 Wegener granulomatosis. A. Chest x-ray and (B) computed tomography: pulmonary hemorrhage manifesting as bilateral central airspace disease (A).

Figure 13.9 Wegener granulomatosis. A. Posteroanterior and (B) lateral chest x-ray: left upper lobe collapse (C), best seen on the lateral radiograph, where the major fissure is displaced anteriorly (arrows). C. Conventional tomogram through the left upper lobe bronchus: marked bronchial narrowing (arrows).

Immune-Complex Vasculitis

Necrotizing Sarcoidal Angiitis

Necrotizing sarcoidal angiitis is distinguished from sarcoidosis by the presence of arteritis. It is a rare disorder, has a mean age at onset of 45 years, and a male-to-female ratio of 1:2.5. In general, this is a benign condition that does not require treatment (1,2,3). Radiologically, the most common pattern is bilateral nodules, occurring in 75% of patients and ranging up to 4 cm in diameter. There is a slight predilection for the lower lobes. Nodules may cavitate and may be miliary. Less common patterns include bilateral airspace disease, basal interstitial abnormality, and pleural effusions (16).

Diffuse Pulmonary (Alveolar) Hemorrhage

Table 13.4 lists the causes of diffuse pulmonary hemorrhage (3).

Table 13.4: Causes of Diffuse Pulmonary Hemorrhage

Antiglomerular basement membrane (Goodpasture disease)
ANCA-associated small vessel vasculitides
   Microscopic polyangiitis
   Wegener granulomatosis
   Churg-Struss syndrome
Immune complex disease/collagen vascular disease
   Systemic lupus erythematosus
   Other CVD (RA, PSS, Polymyositis, Mixed connective tissue disease)
   Henoch-Schonlein purpura
   Antiphospholipid syndrome
   Behçet’s disease
   Mixed cryoglobulinemia
Idiopathic pulmonary hemosiderosis
Coagulopathy
Drugs/chemicals

ANCA, Antinuclear cytoplasmic antibody.

Antiglomerular Basement Membrane Disease (Goodpasture Disease)

Goodpasture disease is a rare disease with an incidence of 1 in two million, a typical age at onset of 20 to 30 years, and a male-to-female ratio of 2 to 9:1. It is rare in African Americans and is essentially a disease of young white males. There is an increased incidence of HLA DR2. When there is pulmonary involvement, it is termed Goodpasture syndrome. Classically, antiglomerular basement membrane disease is a triad of (a) glomerulonephritis, (b) circulating antibodies against the glomerular and alveolar basement membranes, and (c) pulmonary hemorrhage (1,2,20). Usually, IgG causes linear immunofluorescent staining of the basement membranes. Hemoptysis is the most common and earliest feature of Goodpasture disease, typically preceding renal disease by several months. This disease has a poor prognosis, with one series showing 96% mortality and a mean survival of 15 weeks (3). Therapy includes supportive care, plasmapheresis to remove circulating antibodies, and immunosuppression to stop the production of antibodies.

Goodpasture disease affects the lungs and kidneys, but hemoptysis typically precedes renal disease.

Acute pulmonary hemorrhage causes diffuse or sometimes patchy airspace disease, predominantly in a perihilar distribution (Fig. 13.10) and at the lung bases, with sparing of the costophrenic angles and apices. It is asymmetric and often unilateral. On CT, acute pulmonary hemorrhage is often seen as ground glass opacity or airspace disease, patchy or diffuse. With time this is replaced by a reticular pattern that resolves in less than 2 weeks. If there are repeated hemorrhages, interstitial fibrosis can develop, causing a permanent reticular pattern. Hilar lymph nodes may be enlarged during acute episodes (16,20).

Idiopathic Pulmonary Hemosiderosis

This is a rare disease of childhood with the usual age at onset between 1 and 7 years. Only 20% of cases present over the age of 10. In children males and females are equally affected, but for those older than 20 years of age the male-to-female ratio is 2:1. There is an association with celiac disease and dermatitis herpetiformis. Idiopathic pulmonary hemosiderosis is characterized by a triad of (a) pulmonary hemorrhage, (b) iron-deficiency anemia, and (c) immunoallergic reaction with eosinophilia and mastocytosis (1,2,3,4).

Radiologically, abnormalities are identical to those seen in Goodpasture disease, with patchy or diffuse perihilar or basilar airspace disease, in time replaced by a diffuse reticular pattern (Fig. 13.11). With recurrent hemorrhage, generalized fibrosis can occur. HRCT demonstrates patchy or diffuse ground glass opacity or airspace disease in the acute stage, later progressing to fibrosis. Magnetic resonance imaging is particularly useful because of the paramagnetic qualities of intraalveolar hemosiderin, demonstrating high signal on T1 and markedly low signal on T2. This allows a diagnosis of hemorrhage that can aid patient management, especially in the very young (3).

Figure 13.10 Goodpasture disease. Bilateral airspace disease results from pulmonary hemorrhage. Surprisingly, the patient is a woman.

Figure 13.11 Idiopathic pulmonary hemosiderosis. A. Posteroanterior chest x-ray: diffuse abnormality of the lungs, not well characterized. B. High resolution computed tomography: extensive traction bronchiectasis, honeycombing, and interlobular septal thickening from chronic idiopathic pulmonary hemosiderosis.

Hematologic Disorders

Sickle Cell Disease

Sickle cell disease is the term given to the group of disorders characterized by the presence of hemoglobin S (HbS). The homozygous form (HbSS) is known as sickle cell anemia and the heterozygous form (HbSA) is known as sickle trait; there are other heterozygous variants. Up to 13% of African Americans have sickle trait (5). The disease only presents after the sixth month of life when fetal hemoglobin (HbF) is replaced by HbS. Red blood cells containing HbS have reduced oxygen transfer capabilities, and at lower oxygen tensions are less plastic, adopting the characteristic sickle shape. This leads to increased blood viscosity and stasis in areas of slow flow or high metabolism. Sickle cell anemia mainly affects the bones and bone marrow, brain, kidney, and spleen but also has manifestations within the chest (1,2). Findings on the CXR may be cardiac, pulmonary, osseous, and abdominal (Table 13.5).

Chronic anemia may result in cardiomegaly and pulmonary plethora. Sickle cell patients may present with “acute chest syndrome.” This is a triad of (a) fever, (b) clinical findings of a pulmonary process, and (c) radiologic pulmonary disease. This is a frequent cause for hospitalization. Acute chest syndrome results in lobar or segmental airspace disease, atelectasis, and/or pleural effusions. It is caused by pneumonia or infarction, and distinguishing the two can be difficult. Sickle cell patients are at increased risk of infection, especially withStreptococcus pneumoniaeHaemophilus influenza, and Mycoplasma due to autosplenectomy. Salmonella and Staphylococcus infections also occur. Infarction is rare in children, so that acute chest syndrome is usually due to infection. Infarcts are more frequent in adults, although most cases of sickle cell crisis are still due to infection. Imaging for infarction is difficult. Pulmonary angiography is not generally indicated, ventilation-perfusion scanning is often indeterminate, and CT pulmonary angiography may be required. Pulmonary infarct is often associated with evidence of infarction elsewhere, such as in the abdomen, muscle, and bone (3,21,22,23).

Autosplenectomy in sickle cell disease increases the risk of infections caused by S. pneumoniae, H. influenzae, Mycoplasma, Salmonella, and Staphylococcus.

Coarsening and diffuse sclerosis of the thoracic skeleton results from chronic anemia and infarction. Infarcts within the central portions of the vertebral bodies result in H-shaped vertebrae (Fig. 13.12). Periosteal reaction may be due to infarction or infection. Infarcts of the humeral head result in focal sclerosis, called “snow-capping.” Ribs may be shortened (4). Below the diaphragm cholelithiasis or cholecystectomy clips may be noted, because sickle cell patients have an increased incidence of gallstones secondary to increased hemoglobin turnover. Children may have splenomegaly, whereas adults may have a prominent gastric air bubble as a manifestation of autosplenectomy.

Table 13.5: Chest Radiographic Manifestations of Sickle Cell Disease

Lung/pleura
   Consolidation (infection or acute chest syndrome)
   Atelectasis
   Pleural effusion
Cardiac
   Cardiomegaly
   Increased pulmonary blood flow
Osseous
   Osteosclerosis
   Humeral head infarcts (focal sclerosis or periosteal reaction)
   H-shaped vertebral bodies
   Short ribs
Abdominal
   Splenomegaly
   Splenic infarction (small and/or calcified spleen)
   Cholelithiasis

Figure 13.12 Sickle cell disease. Lateral chest x-ray shows typical H-shaped vertebrae (V).

Extramedullary Hematopoiesis

Extramedullary hematopoiesis is the formation of blood outside the bone marrow in the reticuloendothelial organs such as liver, spleen, and lymph nodes. It occurs in severe anemia, usually in congenital anemias such as spherocytosis and sickle cell disease (1,2). The lungs are rarely involved. On CXR or CT, extramedullary hematopoiesis manifests as multifocal smooth paravertebral masses, usually in the lower chest (Fig. 13.13). There may be additional extrapleural masses adjacent to ribs, which may or may not be continuous with the paravertebral masses. Masses can be unilateral or bilateral. They usually do not cause pressure erosion of adjacent bone, a differentiating point from neurogenic tumors (4,24).

Unlike neurogenic tumors, masses of extramedullary hematopoiesis tend not to erode adjacent bone.

Lymphoproliferative Disorders of the Lung

There are many forms of lymphoproliferative disease in the lung (3), with radiologic manifestations including solitary and multiple masses within the lung and/or mediastinum and solitary and multiple lung nodules, areas of ground glass opacity, or consolidation. A list of lymphoproliferative disorders is given in Table 13.6. Lymphoma is discussed in Chapters 8 and 9.

Posttransplant Lymphoproliferative Disorder

Posttransplant lymphoproliferative disorder occurs in 2% of transplant patients, especially heart-lung and renal transplant patients. It is associated with Epstein-Barr infection and immunosuppression. Radiologically, there may be one or multiple nodules and hilar or mediastinal lymph node enlargement (25,26).

 

Lymphoid Interstitial Pneumonitis

Lymphoid interstitial pneumonitis is associated with acquired immunodeficiency syndrome in children and autoimmune and connective tissue disease in adults. Radiologically, it may appear as septal lines, reticulonodular opacities, or nodules. HRCT is particularly useful in its assessment and may demonstrate ground glass opacity (Fig. 13.14). Honeycombing and fibrosis can ultimately occur. Lymphoid interstitial pneumonitis may progress to typical lymphoma (Fig. 13.15). In fact, other than Castleman disease the lymphoproliferative disorders (Fig. 13.16) are now thought to be lymphomas (26).

Figure 13.13 Extramedullary hematopoiesis. A. Posteroanterior and (B) lateral chest x-ray: multilobular bilateral posterior mediastinal masses (H). C. Computed tomography: soft tissue attenuation paravertebral masses (H).

Table 13.6: Lymphoproliferative Disorders of the Lung

Plasma cell granuloma
Posttransplant lymphoproliferative disorder
Lymphoid interstitial pneumonitis
Lymphomatoid granulomatosis
Pseudolymphoma
Angioimmunoblastic lymphadenopathy
Castleman disease

Figure 13.14 Lymphoid interstitial pneumonitis. Ground glass opacity predominantly in the lower anterior lungs.

Leukemia

The leukemias are a heterogeneous group of neoplasms of the hematopoietic cells. They may be of myeloid or lymphoid cell origin and acute or chronic in presentation (Table 13.7). There is an overall incidence of 13 per 100,000, but this varies depending on the specific type of leukemia and the affected age range. Acute leukemias are more common in children and young adults, whereas chronic leukemias are more common in older adults. Abnormalities seen on chest imaging in leukemia can be divided into three categories, as listed in Table 13.8 (1,2,27,28).

Figure 13.15 Lymphoid interstitial pneumonitis/lymphoma. A. Posteroanterior and (B) lateral chest x-ray: mass-like bibasilar airspace disease (L) with air bronchograms (arrows). The biopsy was interpreted as lymphoid interstitial pneumonitis and/or lymphoma, reflecting the overlap of these entities.

Figure 13.16 Pseudolymphoma. Widespread nodular and patchy opacities, with questionable cavities in the right lung.

Leukemic infiltration of the lung is common pathologically but is rarely a cause of significant opacities on the chest radiograph. Lung parenchymal abnormalities are better seen on HRCT, but it can be difficult to diagnose the nature of the abnormality. Hemorrhage and infection cannot be distinguished, and both may resemble leukemic infiltrate (Fig. 13.17). Occasionally, leukemic infiltrates can present with a “tree-in-bud” appearance (29).

T-cell leukemias may show massive mediastinal lymph node enlargement that resolves quickly with treatment. Pleural effusions are common. Subpleural and chest wall deposits may occur, causing extraparenchymal masses that may be associated with rib destruction (called chloromas). Chloromas most commonly occur with myeloid leukemias (3).

Pulmonary infection, hemorrhage, and edema are complications of the disease and also of its treatment. Drug reactions may occur, with alveolitis or pulmonary fibrosis. The CXR is very useful for detecting pulmonary abnormality but less useful for distinguishing the specific etiology (29).

Acute graft-versus-host disease occurs 20 to 100 days after bone marrow transplantation. The effects in the lungs are minimal, with the brunt of the disease affecting skin, gastrointestinal tract, and liver. After 100 days it is termed chronic graft-versus-host disease.

The CXR is frequently normal. When abnormal, there may be diffuse or patchy perihilar airspace disease. More severe disease may result in development of a diffuse interstitial pattern. Bronchiolitis obliterans is the most common finding in chronic graft-versus-host disease and is best appreciated on HRCT with expiratory scanning. This reveals bronchial wall dilation, a mosaic pattern of altered attenuation, and evidence of air trapping on the expiratory scans (30).

Chronic graft-versus-host disease of the lungs is best diagnosed with HRCT that includes expiratory scans.

Table 13.7: Common Leukemias

Myeloid leukemias
   Acute myeloid leukemia
   Chronic myeloid leukemia
Lymphoid leukemias
   Acute lymphoblastic leukemia
   Chronic lymphocytic leukemia
   Hairy-cell leukemia

Table 13.8: Thoracic Leukemia Categories of Abnormality

Leukemic infiltrates of the lung, intrathoracic lymph nodes, pleura, and/or chest wall
Complications of the disease or its treatment
Graft-versus-host disease

Multiple Myeloma

Multiple myeloma is a malignant proliferation of plasma cells from a single clone. It has an incidence of approximately 3 per 100,000, usually presents in the fifth to eighth decade with 98% of patients over the age of 40, and has a male-to-female ratio of 2:1. Blacks have nearly twice the incidence of whites. It is diagnosed by the presence of a monoclonal gammopathy on serum electrophoresis (1,2,5).

Lung involvement is rare. However, thoracic lymph node enlargement and pleural effusions can occur. Myeloma predominantly affects bone; on the CXR this can be seen as generalized osteoporosis of the ribs and vertebral bodies with widespread osteolytic lesions. Expansile lytic rib lesions can occur, as can extrapleural soft tissue masses that erode rib (Fig. 13.18). Plasmacytomas may occur in unexpected locations (Fig. 13.19). In 10% of patients, amyloidosis develops (p. 341).

Figure 13.17 Acute myeloid leukemia. A. Posteroanterior chest x-ray in April: multifocal airspace disease, most visible in the right suprahilar lung (L). Biopsy revealed leukemic infiltration, and abnormality resolved after administration of chemotherapy. B.Posteroanterior chest x-ray in July: new mass-like opacity at right apex (A) proved to be invasive aspergillosis.

Figure 13.18 Multiple myeloma with extraparenchymal mass (M).

Figure 13.19 Tracheal plasmacytoma (P).

Figure 13.20 Metastatic calcifications in chronic renal failure. A. Computed tomography: widespread airspace disease with a somewhat nodular character. B. Radionuclide bone scan: image of the chest reveals bilateral uptake throughout the lungs, creating a “negative image” of the heart (H).

 

Metabolic Diseases

Renal Disease

Nephrotic syndrome and renal failure cause a variety of abnormalities on chest imaging. Both can result in pleural effusions, usually bilateral, due to hypoproteinemia or fluid overload. They can also result in airspace disease on CXR due to fluid, red cells, or white cells in the alveoli. Pulmonary edema can occur secondary to fluid imbalance and hypoproteinemia. Hemorrhage can occur as part of diseases such as Goodpasture disease and Wegener granulomatosis (discussed above) or during anticoagulation for dialysis. Renal patients are subtly immunosuppressed and are more prone to infections, including those with atypical organisms. This is especially true of renal transplant patients on immunosuppressive therapy. Patients with renal failure may also develop pericardial effusions due to uremic pericarditis. Metastatic calcification can occur due to renal impairment with secondary hyperparathyroidism (1,2,3,4,31).

Metastatic Pulmonary Calcification

Metastatic pulmonary or soft tissue calcification can occur in patients with chronic renal impairment, secondary hyperparathyroidism, multiple myeloma, hypervitaminosis D, milk-alkali syndrome, and sarcoidosis. On CXR there is typically persistent airspace disease without clinical evidence of pneumonia or pulmonary edema. In fact, patients are generally minimally symptomatic or asymptomatic. CT may demonstrate that abnormality is high in attenuation. Increased activity on radionuclide bone scan (Fig. 13.20) clinches the diagnosis (1,2,3,4,32).

Liver Disease

Liver disease is a rare cause of pulmonary parenchymal abnormalities. Liver disease can result in hypoproteinemia and/or portal hypertension with pleural effusions, unilateral or bilateral. Reduced clotting factors in cirrhosis can cause pulmonary hemorrhage. Hepatomegaly can cause elevation of the right hemidiaphragm and atelectasis at the right lung base (1,2,3,4).

Amyloidosis

Amyloidosis is the extracellular deposition of proteinaceous twisted β-pleated sheet fibrils. It may be localized or systemic. The classification of amyloidosis is listed in Table 13.9 (1,2,5).

Table 13.9: Classification of Amyloidosis

Systemic
   Primary amyloidosis (AL type)
   Amyloidosis associated with multiple myeloma/Waldenstrom macroglobulinemia (AL type)
   Amyloidosis secondary or reactive to chronic infection and inflammation (AA type)
   Heredofamilial amyloidosis (AA type)
Localized
   Localized amyloidosis (AL type)
   Amyloidosis associated with aging (AL type)

Table 13.10: Thoracic Manifestations of Pulmonary Amyloidosis

Tracheobronchial
   Diffuse airway narrowing
   Multifocal airway narrowing
   Focal endobronchial mass(es)
Nodular parenchymal
   Nodules(s) (+/- calcification)
   Lymph node enlargement (+/- calcification)
   Pleural effusion

Diffuse parenchymal
   Interstitial lung disease (septal lines, honeycombing)

In systemic amyloidosis there may be pathologic involvement of the lungs, but clinical or radiologic manifestations are rare. Most cases of pulmonary amyloidosis are of the localized type, which affects the lung parenchyma and/or the airways. It usually follows one of three patterns, as given in Table 13.10 (5).

Tracheobronchial amyloidosis is the most common type. It may be diffuse or nodular, but diffuse disease is more common. Radiologically, diffuse disease causes multiple eccentric or concentric areas of stricture, sometimes with calcification and typically affecting the trachea or bronchi to the segmental level. In the nodular form, nodules protrude from the trachea and/or main bronchi. The membranous portion of the trachea is involved, in contradistinction to tracheobronchopathia osteoplastica, where the membranous portion is spared (Figs. 13.21 and13.22).

The nodular parenchymal form is less common than the tracheobronchial form and usually occurs in patients less than 60 years old. These patients are often asymptomatic. There may be mediastinal or hilar lymph node enlargement or calcification (Figs. 13.23 and 13.24). The nodules may be single or multiple, tend to have a peripheral or subpleural distribution, and can calcify or ossify (Figs. 13.25 and 13.26). Nodules range in size from 5 mm to 5 cm and are smooth or lobulated in outline. They can be spiculated and may resemble cancer. Pleural effusion is sometimes associated.

Figure 13.21 Tracheobronchial amyloidosis. A. Computed tomography: plaque-like calcification around the entire circumference of the tracheobronchial tree (arrows)B. Coronal reconstruction: marked wall thickening (T) with foci of calcification (arrows).

Figure 13.22 Tracheobronchopathia osteoplastica. A. Posteroanterior chest x-ray: marked narrowing of bronchus intermedius (arrows).B. Computed tomography: calcification (arrows) does not extend around the entire tracheal circumference.

Figure 13.23 Amyloidosis. Enlarged right paratracheal (R) and prevascular (P) lymph nodes with speckled calcification (arrows). (Courtesy of Dr. E. V. Bouffard III, Olney, IL.)

Figure 13.24 Amyloidosis. Enlarged right paratracheal lymph nodes (R) with faintly visible calcification of supraclavicular lymph nodes (arrows).

Figure 13.25 Amyloidosis. Calcified right lung nodule.

Figure 13.26 Amyloidosis. Multiple bilateral lung nodules (N). At computed tomography, several were faintly calcified.

Figure 13.27 Amyloidosis. Extensive bilateral parenchymal involvement. (Courtesy of Dr. Michael Streiter, Huntington, NY.)

Diffuse parenchymal disease is the least common form and usually occurs in patients over age 60. When systemic amyloidosis affects the lungs it usually does so in this form. With diffuse disease, patients are often asymptomatic with normal imaging. When imaging is abnormal, there are often widespread interstitial opacities that may or may not calcify and can become confluent (Fig. 13.27). Honeycombing has been demonstrated (33,34).

Miscellaneous

Langerhans Cell Histiocytosis (Histicytosis X)

This is a poorly understood group of disorders characterized by proliferation of Langerhans cells, possibly due to a defect in immunoregulation. It is subdivided into three separate diseases according to age and severity: Letterer-Siwe disease, an acute disseminated and fulminant form occurring in neonates; Hand-Christian-Schuller disease, a chronic, disseminated, less severe form occurring in children ages 5 to 10 years; and eosinophilic granuloma, the most benign form, occurring in young adults and predominantly affecting the lungs and bones. Lung involvement occurs in 20% of cases and is termed pulmonary Langerhans cell histiocytosis. It has an incidence of 1 to 5 per million and an age at onset of 20 to 40 years. Once thought to be a male-predominant disease, it is now considered equally prevalent in both sexes. This may reflect changing smoking patterns, because there is a strong association with cigarette smoking. It is much rarer among African Americans (1,2,3,5).

Because it is strongly associated with cigarette smoking, eosinophilic granuloma has changed from a male-predominant to a gender-neutral disease.

The lungs are initially involved, with multiple upper lobe stellate nodules of 3 to 10 mm, sparing the costophrenic angles. This is the granuloma stage. On HRCT these nodules have a centrilobular peribronchiolar distribution with normal intervening lung. Cavitation is uncommon. Small irregular cysts are also seen. HRCT is extremely useful in the evaluation of the nodules and cysts (Fig. 13.28). Alveolar consolidation is rare but can occur when the alveoli fill with histiocytes and eosinophils. Abnormality progresses to a reticulonodular pattern and finally culminates in fibrosis, large cystic spaces, and honeycombing. Volume loss is uncommon, and one-third actually have increased lung volumes. Spontaneous pneumothorax is very common (35).

Rib involvement results in well-defined osteolytic lesions, which may be expansile (Fig. 13.29). Involvement of vertebral bodies may cause severe collapse with vertebra plana.

Figure 13.28 Pulmonary Langerhans cell histiocytosis. High resolution computed tomography with multiple upper lobe cysts and scattered irregular lung nodules (arrows).

Figure 13.29 Pulmonary Langerhans cell histiocytosis. A. Computed tomography at soft tissue window settings: expansile lytic right anterolateral rib lesion (E). B. Computed tomography at lung window settings, more cephalad than A: numerous lung cysts, with scattered lung nodules.

The Phakomatoses

Table 13.11 lists these disorders.

Neurofibromatosis (von Recklinghausen Disease)

Neurofibromatosis type 1 (von Recklinghausen disease) is an autosomal dominant disease. It has an incidence of 1 per 3,000, half of cases are sporadic mutations, and there is no gender or racial predominance. The abnormal gene is located on chromosome 17. There is an association with multiple endocrine neoplasia type IIb (pheochromocytoma, medullary thyroid carcinoma, and multiple neuromas). There is also a 10-fold increase in the incidence of congenital heart disease (1,2,5). Neurofibromatosis has a variety of manifestations in the chest and can cause chest wall involvement, mediastinal masses, and lung involvement

Cutaneous tumors can be seen as nodules on the CXR. If they are projected outside the lungs, a diagnosis of cutaneous nodules can easily be made, but otherwise they can be mistaken for pulmonary nodules. Neural tumors can arise from chest wall (Fig. 13.30) or intercostal nerves, and if they are large enough they may erode ribs and cause rib notching (Fig. 13.31). The ribs themselves may be abnormal, being thin and/or twisted (ribbon ribs). Kyphoscoliosis of the thoracolumbar spine occurs in 10% to 60% of patients. There may also be developmental and modeling abnormalities of vertebrae such as posterior vertebral scalloping, enlargement of intervertebral foramina, and absence or remodeling of pedicles (36,37).

Neural tumors, especially neurofibromas, neurilemmomas, schwannomas, and their malignant counterparts, may arise in the middle mediastinum. They can be localized or diffuse. They are more common on the left. They often arise from the vagus nerve and present as slowly growing, smoothly marginated, middle mediastinal masses that are often low in attenuation on contrast-enhanced CT but may be of muscle attenuation. Nerve sheath tumors are not reliably differentiated on CT. On magnetic resonance imaging neurofibroma and schwannoma are isointense with nerve tissue on T1-weighted imaging and high signal intensity on T2-weighted imaging. Although they may be asymptomatic, large lesions can cause local compression. Malignant transformation is possible (3). Posterior mediastinal masses are even more common and may be neural tumors, lateral meningoceles, or rarely pheochromocytomas. Lateral meningoceles usually occur at the apex of kyphoscoliosis and are more common on the right. They are associated with the vertebral developmental and modeling abnormalities mentioned above.

Table 13.11: Neurocutaneous Disorders

Neurofibromatosis (von Recklinghausen disease)
Tuberous sclerosis (Bourneville disease)
Cerebelloretinal hemangioblastosis (von Hippel-Lindau syndrome)
Encephalotrigeminal syndrome (Sturge-Weber disease)
Ataxia telangiectasia (Louis-Bar syndrome)
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Figure 13.30 Chest wall neurofibroma (N) on (A) posteroanterior chest x-ray, (B) lateral chest x-ray, and (C) computed tomography.

Figure 13.31 Neurofibromatosis with rib notching (arrows).

Lung parenchymal involvement has a prevalence of 20%, affecting men and women equally and taking the form of a basal predominant interstitial fibrosis with upper and mid-lung thin-walled bullae. Neural tumors may simulate lung nodules, and their malignant counterparts may metastasize to the lungs (3,36).

Tuberous Sclerosis (Bourneville Disease)

Tuberous sclerosis is an autosomal dominant disorder with a low penetrance. The abnormal gene is located on chromosome 16, and spontaneous mutations occur in 50% to 80%. Tuberous sclerosis is characterized by a triad of (a) adenoma sebaceum, (b) seizures, and (c) mental retardation. Tuberous sclerosis has an incidence of 7 per million and occurs equally in males and females (1,2).

Pulmonary involvement occurs in 1% to 2% of cases. Pulmonary findings on CXR and HRCT are indistinguishable from those in lymphangiomyomatosis, except for the absence of pleural effusion. Spontaneous pneumothorax often occurs. Tuberous sclerosis causes interstitial disease, with a reticular or reticulonodular CXR appearance (Fig. 13.32). The nodules are small (1 to 2 mm). With time the reticular elements become more marked, with honeycombing and cyst formation. The cysts are usually less than 1 cm and are smooth-walled and uniform. The lung volumes are normal or enlarged due to air trapping and focal emphysema. Bone cysts or sclerotic vertebrae may be seen (36,38,39). Associated renal angiomyolipomas may help to establish the diagnosis in equivocal cases (Fig. 13.32).

Interstitial lung disease in tuberous sclerosis is indistinguishable from that in lymphangiomyomatosis, except for the absence of pleural effusion in tuberous sclerosis.

Lymphangiomyomatosis

Although not a neurocutaneous disorder, the pulmonary features of lymphangiomyomatosis are virtually identical to tuberous sclerosis. Lymphangiomyomatosis is characterized by a triad of (a) gradually progressive interstitial lung disease with uniform smooth-walled cysts (Fig. 13.33), (b) recurrent chylous pleural effusions, and (c) recurrent pneumothoraces. It is a rare disorder, has an age at onset between 17 and 50 years, and occurs exclusively in women. At HRCT there are numerous small cysts, as in pulmonary Langerhans cell histiocytosis (Fig. 13.34). The cysts in lymphangiomyomatosis are more uniform in size and shape and more diffusely distributed (without the upper lobe predominance of pulmonary Langerhans cell histiocytosis). In addition, pulmonary Langerhans cell histiocytosis often demonstrates associated lung nodules, which are not a feature of lymphangiomyomatosis (1,2,3).

Ataxia Telangiectasia (Louis-Bar Syndrome)

Ataxia telangiectasia is an autosomal recessive disorder characterized by telangiectasias of the skin and eye, cerebellar ataxia, sinus and pulmonary infections, immunodeficiency, and a propensity to develop malignancies. It has an incidence of 1 in 40,000 and occurs equally in males and females (1,2). On the CXR there may be airspace disease due to infection. With repeated infections, linear fibrotic changes and bronchiectasis tend to occur. Lymph node enlargement is usually absent; its presence may indicate malignancy. Bronchiectasis with respiratory failure is the most common cause of death (36,40).

Figure 13.32 Tuberous sclerosis. A. Posteroanterior chest x-ray: basilar honeycombing. B. Computed tomography: large exophytic left lower pole renal mass (A) with foci of fat (arrows) compatible with angiomyolipoma. C. Subtraction view of left renal angiogram: vascular mass (A) is angiomyolipoma.

Figure 13.33 Lymphangiomyomatosis. Chest x-ray with multiple cysts, giving the appearance of honeycombing.

Figure 13.34 Spectrum of severity of lymphangiomyomatosis. A. Mild lymphangiomyomatosis: scattered cysts (arrows) at high resolution computed tomography, many too small to denote with an arrow. B. Moderate lymphangiomyomatosis: more numerous cysts in a different patient. C. Severe lymphangiomyomatosis: a third patient with innumerable cysts.

 

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)

Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder with incomplete penetrance and variable expression. Nearly 90% of pulmonary arteriovenous fistulas (arteriovenous malformations) are associated with this disease, especially if multiple. Arteriovenous malformations and telangiectasias can affect the nasal mucosa, skin, lung, central nervous system, gastrointestinal tract, and liver. Patients may have cyanosis, clubbing, and polycythemia. They frequently present with epistaxis, hemoptysis, or hematemesis. Cerebral abscesses or infarcts commonly occur due to right-to-left shunting. Up to one-third of patients have strokes, either due to a bleeding arteriovenous malformation or infarct (1,2).

Nearly 90% of pulmonary arteriovenous malformations occur in the setting of Osler-Weber-Rendu syndrome.

On the CXR arteriovenous malformations present as well-demarcated lobulated nodules (Fig. 13.35) (Chapter 21Fig. 21.29). A draining vein and a feeding artery may be identified, resembling “rabbit ears” or an antenna. Contrast-enhanced CT or pulmonary angiography is helpful in identifying lesions not seen on CXR (Fig. 13.35C). Pulmonary angiography is vital for planning treatment. Although 80% of lesions are simple (one feeding vessel), 20% will have two or more feeding vessels. Feeding vessels less than 3 mm in size are generally not treated. Vessels are occluded with detachable balloons or coils. Larger lesions may require surgery (3,41).

Sarcoidosis

Sarcoidosis has an incidence of 2 to 10 per 100,000, with a typical age at onset between 20 and 30 years, with a second peak in the sixth decade, and male-to-female ratio of 1:2 to 3. Although an equal incidence is noted in white men and women, it is up to 10 times more common in black women than black men and 17 times more common in blacks than whites. There is an increased incidence in people with blood group A. Sarcoidosis may also be familial.

Figure 13.35 Osler-Weber-Rendu syndrome. A. Posteroanterior chest x-ray: one right lung nodule (A) with visible feeding artery and draining vein (arrows)B. Right pulmonary arteriogram: arteriovenous malformation (M) accounts for right lung nodule. C. Left pulmonary arteriogram: unexpected small left lung arteriovenous malformation (arrow).

Sarcoidosis is a chronic multisystem disorder of unknown etiology characterized by noncaseating epithelioid cell granulomas, usually presenting with fever, malaise, polyarthralgias (ankles and knees), erythema nodosum, and bilateral hilar and mediastinal lymph node enlargement. Although sarcoidosis predominantly affects the chest, it is a multisystemic disease and affects the skin in up to 70% of cases, with erythema nodosum, lupus pernio, or scar infiltrates. Generalized lymph node enlargement occurs in 30% of patients, with myopathy in 25%. The eyes are involved in 15% (uveitis or keratoconjunctivitis), hepatosplenomegaly is seen in 10%, the bones are involved in 5% to 10%, parotitis occurs in 5%, and the central nervous system is involved in 3% to 5% (1,2,3,5). On the CXR sarcoidosis may affect lymph nodes, lung parenchyma, airways, vessels, pleura, bones, and liver and spleen. There is a staging system for thoracic sarcoidosis that is based on the chest radiograph (Table 13.12).

Table 13.12: Chest Radiography Staging of Sarcoidosis

 

Lymph Node Enlargement

Interstitial Lung Disease

Stage 0

No

No

Stage 1

Yes

No

Stage 2

Yes

Nonfibrotic

Stage 3

No

Nonfibrotic

Stage 4

No

Fibrotic

The triad of bilateral hilar lymph node enlargement and (right) paratracheal lymph node enlargement (Garland triad or 1-2-3 sign) is seen in up to 80% of patients, making it the most common intrathoracic manifestation of sarcoidosis. Lymph node enlargement ranges from just detectable to massive and is usually lobulated and well marginated. Symmetry is an important diagnostic feature, because symmetry is not as common a feature of the major diagnostic alternatives (lymphoma, tuberculosis, and metastatic disease) (3,42). In addition to hilar and paratracheal lymph nodes, other lymph nodes may be affected. Anterior mediastinal and subcarinal lymph node enlargement is common but may be difficult to appreciate on the CXR. It is readily apparent on CT. Posterior mediastinal lymph node enlargement is uncommon. Abdominal lymph nodes are occasionally enlarged (Fig. 13.36).

The triad of bilateral hilar and right paratracheal lymph node enlargement is seen in up to 80% of sarcoidosis patients.

In most patients (60% to 70%), lymph node enlargement completely resolves. This is especially true in patients with erythema nodosum and arthralgias. In the remainder, lung disease develops. Lymph node enlargement is often decreased by the time lung disease is seen. Interstitial lung disease in sarcoidosis is initially not fibrotic, but fibrotic lung disease may develop once lymph node enlargement has resolved. Lymph nodes can show calcification, and this may be in an eggshell pattern (Fig. 13.37) (42). Sarcoidosis is the most common cause of eggshell calcification of lymph nodes after pneumoconiosis (silicosis and coal worker’s pneumoconiosis). The radiologic manifestations within the lung parenchyma are discussed in greater detail in Chapter 14.

Sarcoidosis of the larynx occurs infrequently. Thoracic lymph node enlargement may cause compression of the trachea or bronchi. Tracheal involvement is rare, but when it occurs it results in strictures, which may be smooth, irregular, or nodular. Although peribronchial and perivascular granulomatous infiltration is common, symptomatic bronchial obstruction is not. Traction bronchiectasis occurs with pulmonary fibrosis.

Large vessel arteritis is rare; arteritis of small vessels is more common, often with granulomas. This may result in vessel narrowing but usually does not cause vascular necrosis or thrombosis. Coronary artery involvement has been described. Aortic involvement, either aneurysmal dilation or else stenosis and occlusion with a clinical picture similar to Takayasu arteritis, is rare. Pulmonary arteritis or extrinsic compression by enlarged lymph nodes is similarly rare. Although mediastinal lymph node enlargement may be massive, superior vena cava syndrome is very rare. Myocardial involvement may result in ventricular arrhythmias or heart block, cardiomyopathy, and congestive failure (42).

Figure 13.36 Sarcoidosis. Computed tomography with numerous enlarged abdominal lymph nodes (N).

Figure 13.37 Sarcoidosis. A. Posteroanterior chest x-ray 1963: enlarged, lobular bilateral hila (H) with ill-defined parenchymal abnormality extending into the perihilar lungs, typical of stage 2 sarcoidosis. B. Posteroanterior chest x-ray 1978: lung disease has resolved, and there is now bilateral eggshell calcification of hilar lymph nodes (arrows).

Granulomas may be found on the visceral or parietal pleura, but clinical or radiologic manifestations are uncommon. Pleural effusion occurs in only 2% of patients. Sarcoidosis of bone occurs in 5% to 20% of patients. The phalanges are usually affected, and bone changes on CXR are rare. Although histologic involvement of the liver is common in sarcoidosis (60% to 90%), it is seldom of clinical or radiologic significance (Fig. 13.38). The same applies to the spleen, although splenomegaly occurs in 10% of patients and splenic rupture can occur. Diffuse heterogeneous nodularity of the spleen is also rarely present (3,42).

Figure 13.38 Sarcoidosis with numerous tiny lesions throughout the liver (L) and larger lesions in the spleen (S).

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