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Chronic diffuse interstitial lung diseases are noninfectious disorders characterized by diffuse inflammation and fibrosis involving the interstitium of the alveolar septum (Figure 35-8). The end stage is associated with extensive parenchymal destruction, fibrosis, and often the formation of abnormal cystic spaces (honeycomb lung).
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General Clinical & Pathologic Features
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Patients with diffuse interstitial lung disease present with dyspnea, tachypnea, and cyanosis. Pulmonary function abnormalities are of the restrictive type, with reduced vital capacity but no airway obstruction. The FEV1:FVC ratio is normal. Thickening of the alveolar membrane affects diffusion of oxygen, leading to hypoxemia. This stimulates the respiratory center, resulting in increased ventilation. Carbon dioxide, which is much more diffusible than oxygen, is washed out, resulting in lowered Pco2 levels. Chest x-ray shows a characteristic reticulonodular pattern of interstitial involvement.
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Diffuse infiltrative lung disease has many causes (Table 35-4). While all produce the general picture described above, some have individual features that permit specific diagnosis.
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Immunologic Interstitial Pneumonitis & Fibrosis
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Idiopathic Pulmonary Fibrosis (Fibrosing Alveolitis; Hamman-Rich Syndrome)
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Idiopathic pulmonary fibrosis is actually a group of diseases characterized by diffuse interstitial fibrosis occurring without recognized cause. About half the cases of chronic diffuse interstitial lung disease fall into this category. Alhough the cause is unknown, the presence of circulating immune complexes, immunoglobulin deposition in the interstitium in many patients, and the response of early disease to treatment with steroids strongly suggest an immunologic basis.
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The alveolar macrophage is thought to be responsible for mediating fibrosis. In idiopathic pulmonary fibrosis, alveolar macrophages express several genes that encode for mediators such as fibronectin and platelet-derived growth factor that recruit and stimulate fibroblasts. The production of platelet-derived growth factor by alveolar macrophages in idiopathic pulmonary fibrosis correlates with activation of the c-sis gene in these cells. The c-sis gene encodes for the B chain of platelet-derived growth factor.
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Clinically, patients present with progressive dyspnea and cough and ventilatory failure of the restrictive type. A defect in oxygen diffusion across the abnormal alveolar membrane may also contribute. The rate of progression is quite variable; a rapidly progressive variant that may cause death in 1–2 years is sometimes called Hamman-Rich syndrome.
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Idiopathic pulmonary fibrosis is classified according to the histologic appearance of the lung, as discussed below.
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Usual Interstitial Pneumonitis
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This accounts for the majority of cases. In the acute phase, there is interstitial infiltration with lymphocytes, plasma cells, and macrophages; pulmonary edema; acute alveolar damage; and proteinaceous hyaline membranes. The damaged alveoli are lined by type II pneumocytes, which can appear so atypical cytologically as to mimic the appearance of an adenocarcinoma. In the acute phase, the disease may respond to treatment with immunosuppressive agents such as corticosteroids. The acute phase is followed by proliferation of fibroblasts and laying down of collagen in the alveolar interstitium (Figure 35-8). The rate of fibrosis is variable, but the occurrence of fibrosis represents irreversibility.
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The course is characteristically protracted, with respiratory failure occurring many years after onset. When interstitial fibrosis (honeycomb lung) is present, the clinical response to steroids is poor.
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Desquamative Interstitial Pneumonitis
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The desquamative form is similar to the foregoing except for the aggregation of desquamated cells in alveoli—a variable mixture of macrophages and type II pneumocytes. Controversy exists about whether this is a variant of usual interstitial pneumonitis or a completely different disease. The course is similar to that of slowly progressive usual interstitial pneumonitis.
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Lymphocytic Interstitial Pneumonitis (Pseudolymphoma)
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Lymphocytic interstitial pneumonitis is characterized by extensive infiltration of the interstitium with lymphocytes and plasma cells. It may be diffuse or may involve a single area of lung, producing a mass lesion (pseudolymphoma). The disorder is associated with an increased incidence of primary pulmonary malignant lymphoma; in some cases, the process appears to be a primary low-grade malignant lymphoma.
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Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)
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Hypersensitivity pneumonitis results from inhalation by susceptible individuals of small organic particles (antigens), most commonly spores of thermophilic fungi. These fungi grow best at 50–60 °C in decaying vegetation such as hay and sugar cane or in heated water in air-conditioning and heating systems.
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Individuals working in a variety of occupations are at risk, and the disease frequently bears the name of these occupations (see Chapter 8: Immunologic Injury). Thermophilic actinomycete spores occur in moldy hay (farmer's lung), moldy sugar cane residue (bagassosis), and compost for mushroom growing (mushroom worker's disease). In urban areas, the spores are most frequently found in contaminated forced-air-heating and air-conditioning systems. Antigenic products are also found in bird droppings (bird-fancier's lung), dead wood (maple bark stripper's disease), and barley malt used in brewing (malt worker's lung).
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Hypersensitivity pneumonitis is caused by a combination of type III hypersensitivity associated with precipitating IgG antibodies, which are present in the serum of 70% of patients, producing a local Arthus type immune complex reaction with complement deposition in the lung; and T lymphocyte-mediated type IV hypersensitivity, leading to the formation of small, noncaseating epithelioid cell granulomas in the alveolar septa (Table 35-5). Bronchoalveolar lavage demonstrates an increase in T lymphocytes.
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Hypersensitivity pneumonitis is characterized by an acute interstitial pneumonitis. The alveolar septa are expanded by neutrophils, lymphocytes, and plasma cells. Poorly formed alveolar granulomas with giant cells are typically present. Fibrous obliteration of bronchioles (bronchiolitis obliterans) is a characteristic change.
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If the disease is recognized early and the patient removed from the source of antigen, the disease is reversible. With continued exposure, diffuse interstitial fibrosis occurs, leading to end-stage honeycomb lung. As fibrosis becomes more advanced, the disease becomes irreversible.
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Patients present with acute dyspnea, fever, and cough 4–6 hours after exposure to the antigen. Initially, these symptoms subside spontaneously in 12–18 hours. As pulmonary fibrosis ensues, the disease goes into its chronic phase, with all the features of diffuse interstitial lung disease.
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Eosinophilic Pneumonias
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Eosinophilic pneumonias are a group of diseases characterized by eosinophilic pulmonary interstitial infiltrates and peripheral blood eosinophilia. These disorders may be idiopathic or may be due to (1) allergic bronchopulmonary aspergillosis, in which there is also bronchial asthma, elevated serum IgE, and evidence of bronchial infection by Aspergillus fumigatus; (2) parasitic (larval) infections, including filariasis, ascariasis, and strongyloidiasis; or (3) drug reactions to nitrofurantoin, sulfonamides, penicillin, gold, and antituberculous agents.
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Idiopathic eosinophilic pneumonia may be acute and self-limiting, with minimal clinical effect (Löffler's syndrome), or chronic, with cough, fever, and weight loss lasting several months (chronic eosinophilic pneumonia).
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Allergic angiitis and granulomatosis of Churg and Strauss shows features of eosinophilic pneumonia with asthma combined with a multisystem vasculitis that frequently involves the skin, kidney, and nervous system. Allergic angiitis and granulomatosis of Churg and Strauss is a serious disease with a high mortality rate and requires aggressive immunosuppressive therapy.
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Interstitial Pneumonitisin Connective Tissue Diseases
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Diffuse interstitial pneumonitis with fibrosis leading to honeycomb lung indistinguishable from usual interstitial pneumonitis occurs in progressive systemic sclerosis (scleroderma) and rheumatoid arthritis. Systemic lupus erythematosus may also be complicated by immune complex deposition in the alveoli, transient patchy lung infiltrates, vasculitis, and acute alveolar damage.
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Goodpasture's Syndrome
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Goodpasture's syndrome is a rare disease characterized by a combination of hemoptysis and pulmonary infiltrates, glomerulonephritis, and the presence of anti-basement membrane antibodies in the circulation. There is a striking male predominance.
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The circulating anti-basement membrane antibody, which is thought to be an autoantibody, fixes onto the basement membrane of pulmonary alveoli and renal glomeruli, causing a complement-mediated type II hypersensitivity reaction (Table 35-5). Immunofluorescence shows linear deposition of IgG and complement in the alveoli, a finding that is diagnostic of Goodpasture's syndrome. In the lung, hemorrhage into the alveoli is the dominant feature; hemosiderin-containing macrophages may be found in the sputum.
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In the acute phase, the lungs are grossly consolidated, heavy, and hemorrhagic. In the chronic phase, the lung is firm because of marked interstitial fibrosis, brown because of hemosiderin, and may show changes of honeycomb lung.
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Onset is most frequently in the second or third decade of life. Patients present with recurrent hemoptysis. Massive pulmonary hemorrhage occurs rarely.
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In the chronic phase, there is progressive dyspnea, cough, and right heart failure due to pulmonary fibrosis. Iron deficiency anemia may result from chronic blood loss. Chest x-ray shows pulmonary infiltrates due to intra-alveolar hemorrhage. Changes of increasing pulmonary fibrosis dominate chronic disease.
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Patients almost invariably have evidence of glomerulonephritis, most frequently microscopic hematuria. In many cases of Goodpasture's syndrome, the renal disease dominates the clinical picture and generally determines the prognosis, which is poor. Renal changes are described in Chapter 48: The Kidney: II. Glomerular Diseases. Treatment by plasmapheresis (to remove the antibody) and steroids has proved effective in a minority of cases.
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Idiopathic Pulmonary Hemosiderosis
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Idiopathic pulmonary hemosiderosis is morphologically identical to Goodpasture's syndrome and considered by some to be a variant of Goodpasture's syndrome without renal involvement. It differs from Goodpasture's syndrome in that it tends to affect a younger age group; there is no male preponderance; and anti-basement membrane antibodies cannot be demonstrated in the blood, although they are present on the alveolar membranes.
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Pneumoconioses (Inorganic Dust Diseases)
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The term pneumoconiosis literally means “dust in the lungs” and denotes pulmonary disease secondary to inhalation of various inorganic dusts (Table 35-6). Changes that occur in the lung vary with the type and amount of dust inhaled, particle size, and the presence of other lung diseases, most importantly those associated with cigarette smoking. Genetic factors play an uncertain role in susceptibility. Some dusts such as coal dust do not evoke a fibrous response (noncollagenous pneumoconioses), whereas others such as silica do (collagenous pneumoconioses). In some patients, inhalation of several different kinds of dust results in mixed disease (eg, anthracosilicosis).
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There is a variable latent period between exposure to dust and onset of clinical disease that may be as long as 20–30 years. Rarely, acute disease develops within weeks after a massive exposure.
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Coal Worker's Pneumoconiosis (Anthracosis)
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Anthracosis results from exposure to coal (carbon) dust and is seen in its most extensive form in coal miners and workers in old coal-burning railways. Lesser degrees of anthracosis occur in almost all urban dwellers.
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The basic pathologic lesion is the coal dust macule, which is a collection of carbon-laden macrophages around the respiratory bronchiole (Figure 35-9). This dust accumulation induces only a very small amount of delicate fibrosis. There may also be insignificant dilation of the respiratory bronchiole (“focal dust emphysema”). There are usually no symptoms and no detectable abnormalities in lung function.
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Rarely, coal workers develop progressive massive fibrosis when heavy exposure is coupled with a complicating factor such as infection with Mycobacterium tuberculosis (found in 40% of patients with massive fibrosis), significant silica contamination (silica induces fibrosis), or development of allergic responses to various proteins that have passively adsorbed onto the coal dust. Progressive massive fibrosis is characterized by the presence of multiple irregular, firm, homogeneous black fibrous masses in both lungs.
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There is also a peculiar relationship between coal workers' pneumoconiosis and rheumatoid arthritis. When coal miners develop rheumatoid arthritis, they tend to develop large rheumatoid nodules in the lung (Caplan's syndrome).
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Silicosis is caused by inhalation of crystalline silicon dioxide (silica) dust particles in the range of 1–5 μm. Silica exists in nature as quartz, chrystobalite, and tridymite. Occupations at increased risk for silicosis are hardrock, gold, tin, and copper mining; sand-blasting; and iron, steel, and granite working. More than 1 million workers in the United States are at risk for developing silicosis. Significant pulmonary disease usually occurs with 10–15 years of exposure but may rarely occur after as little as 1 year. Silicotic lesions may be found long after exposure has been terminated.
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Small silica crystals, when inhaled, reach the lung acinus. Larger crystals (> 5 μm) are caught in the bronchial mucus layer and wafted upward by the ciliary action to be expelled; particles less than 1 μm remain airborne and are exhaled.
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In the alveoli, the silica crystals are phagocytosed by macrophages. Silica is toxic to the internal organelle membranes of the macrophages and causes phagolysosomal disruption, cell death, and liberation of free silica particles. Inflammation and fibrosis follow, leading to formation of a nodule composed of hyalinized collagen around the crystals (Figure 35-10). Silica crystals are also carried in lymphatics to the hilar lymph nodes, where similar silicotic nodules form. One hypothesis suggests that fibrosis is the result of a fibroblast-stimulating factor liberated by macrophages upon phagocytosis of silica particles. A second hypothesis attributes fibrosis to a lymphokine produced by silica-activated T lymphocytes.
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Grossly, the silicotic nodule is gray-black (due to associated carbon pigment), hard, and brittle and has concentric rings of hyalinized collagen in cross section. Nodules are found mainly along lymphatic pathways, especially around the hilum and in the upper lobes. Microscopically, the nodules are composed of a solid mass of macrophages, fibroblasts, and collagen (Figure 35-10). Silica particles are recognized as birefringent needle-shaped crystals in the nodules when examined by polarized light.
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Silicosis is often asymptomatic, being found incidentally at chest x-ray or histologic examination of lungs and hilar lymph nodes removed for an unrelated reason. Rarely, when patients are exposed to massive amounts of dust, acute lung disease may occur, with alveolar thickening and accumulation of proteinaceous material in the alveoli (acute silicotic proteinosis). More often, there is chronic pulmonary fibrosis with a mild restrictive ventilatory defect, slowly progressive dyspnea, and pulmonary hypertension (cor pulmonale).
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Progressive massive fibrosis may complicate chronic silicosis, particularly when the level of exposure to dust is high. The disorder is characterized by confluence of silicotic nodules into large masses of fibrous tissue that cause obliteration of vessels and bronchioles. Central necrosis and cavitation may occur in these masses as a result of ischemia. Progressive massive fibrosis commonly involves the upper lobes and is associated with a significant ventilatory defect and respiratory failure.
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Patients with silicosis have a greatly increased incidence of tuberculosis, believed to be due to the adverse effects of silica dust on macrophage function. Tuberculosis causes extensive necrosis in the nodules, and large numbers of tubercle bacilli can be found in such lesions.
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Silicosis is also associated with an increased incidence of autoimmune disease, especially progressive systemic sclerosis.
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Asbestos is a fibrous silicate found in nature as the minerals chrysotile, amosite, and crocidolite. It is present in such diverse components of the modern environment as insulation, flame retardants, flooring and roofing materials, water and sewage pipes, and brake linings in vehicles, making low-grade exposure almost universal among urban dwellers. It is estimated that up to 11 million workers in the United States have had significant asbestos exposure since 1940.
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Asbestos-related disease was first recognized in those with the highest levels of exposure, ie, workers in shipyards and the construction industry. Approximately 40% of World War II shipyard pipe fitters now have evidence of asbestosis. It is becoming clear, however, that lower levels of exposure are also associated with significant risk. Asbestos-related neoplasms occur in families of shipyard workers—due presumably to the presence in the home of contaminated clothing—and in communities with asbestos-based industries (air pollution by asbestos dust). It is estimated that about 10,000 deaths every year in the United States are due to asbestos-related diseases.
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One of the most common changes associated with asbestos exposure is thickening of the parietal pleura by a plaque-like deposition of hyalinized collagen, maximal in the lateral and diaphragmatic pleura. This change on chest x-ray provides epidemiologic evidence of significant asbestos exposure. Pleural fibrosis does not cause symptoms and does not fall within the definition of asbestos pneumoconiosis because it does not involve lung parenchyma.
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Asbestos fibers, when inhaled into the alveoli, are taken up by macrophages and evoke a diffuse interstitial fibrosis. The mechanism of stimulation of pulmonary fibrosis by asbestos is poorly understood. Asbestos, unlike silica, is not cytotoxic to macrophages; there is evidence of activation of macrophages by asbestos. Asbestos, when added to in vitro cultures of fibroblasts, stimulates increased collagen synthesis by these cells. Initially, fibrosis occurs around bronchioles but eventually extends into the alveolar interstitium. Advanced asbestosis causes end-stage fibrosis (honeycomb lung).
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Microscopically, asbestos fibers are visible as ferruginous bodies (asbestos bodies) composed of a thin central asbestos fiber 5–10 μm long encased in an iron-containing glycoprotein coat which is brown and typically beaded (shish kebab appearance; Figure 35-11). Ferruginous bodies are best seen in sections that have been stained for iron with Prussian blue. While ferruginous bodies are most commonly seen in asbestosis, they are not diagnostic because a similar iron-glycoprotein coat may form on other types of inhaled fibers.
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Asbestos fibers that do not have the iron-glycoprotein coat are not visible microscopically, but they outnumber coated fibers 10:1. The amount of asbestos in the lung thus cannot be accurately estimated by microscopy. A quantitative evaluation of asbestos is best made by chemical analysis of lung tissue.
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Asbestos-induced lung disease presents with the features of diffuse interstitial lung disease, ie, chronic cough, progressive dyspnea, a diffuse infiltrative pattern on chest x-ray, decreased vital capacity with no obstructive element, and blood gas changes of restrictive lung disease (hypoxemia with a normal or reduced arterial Pco2). Asbestosis rarely causes sufficient lung destruction to result in respiratory failure.
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The most significant effect of asbestos exposure is the greatly increased risk of malignant neoplasms. (1) Bronchogenic carcinoma is the most common neoplasm associated with asbestosis. Cigarette smoking has a profound additive effect to asbestos exposure in causing bronchogenic carcinoma. (2) Malignant mesothelioma of the pleura, peritoneum, and pericardium, although less common than bronchogenic carcinoma, represents the most specific neoplasm associated with asbestos exposure; most patients with malignant mesotheliomas give a history of asbestos exposure. Malignant mesothelioma has a 100% mortality rate, and 90% of patients die within 2 years of diagnosis.
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Berylliosis is rarely seen today because beryllium use has declined. Beryllium was used in the past in fluorescent lights and in the aerospace industry.
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Acute exposure to beryllium results in a nonspecific acute pneumonitis. Chronic exposure is characterized by pulmonary fibrosis and the formation of noncaseating epithelioid cell granulomas resembling those of sarcoidosis. Beryllium can be demonstrated in these lesions as refractile crystalline material using polarized light. The formation of granulomas is due to activation of helper T cells in the lung as a direct result of beryllium exposure in susceptible individuals.
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The diagnosis is made by a history of exposure and confirmed by chemical analysis of lung tissue.
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Iatrogenic Drug-, Chemical-, or Radiation-Induced Interstitial Fibrosis
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A large number of drugs—notably the anticancer drugs bleomycin, busulfan, melphalan, methotrexate, and cyclophosphamide—cause diffuse interstitial pulmonary disease with fibrosis. The pulmonary changes are usually dose-related. Lung fibrosis occurs insidiously, often appearing several months after treatment. The fibrosis progresses even after the drug is withdrawn and may cause death if excessive dosages of the drug have been used.
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Paraquat, a commonly used herbicide, causes a severe toxic reaction in the lung when ingested or inhaled. In the acute phase there is pulmonary edema, hemorrhage, and interstitial inflammation. This progresses rapidly to interstitial pulmonary fibrosis, often leading to respiratory failure and death.
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Radiation pneumonitis may complicate cancer therapy if the lungs are included in the field of radiation. High doses cause acute radiation pneumonitis, characterized by necrosis of epithelial cells, intra-alveolar hemorrhage, and formation of hyaline membranes. With lower doses, chronic pulmonary fibrosis occurs.
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Toxic gases (mustard gas, 100% oxygen) also produce diffuse fibrosis that may be severe.
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The pulmonary fibrosis that complicates intravenous heroin use by addicts may be more a response to impurities in the injected material than to the heroin itself. Foreign body granulomas are commonly present in the thickened alveolar septa in addicts who use intravenous drugs.
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Interstitial Diseases of Uncertain Etiology
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Sarcoidosis is a systemic disorder of uncertain cause that is commonly manifested in the lungs. Although the cause is unknown, immunologic mechanisms have been implicated, and abnormalities of the immune system are usually present: (1) Depressed cell mediated immunity is manifested by decreased numbers of T cells in the peripheral blood and by anergy (failure of delayed hypersensitivity to antigens injected in intradermal skin tests). (2) Exaggerated T helper cell activity at sites of disease, associated with the formation of epithelioid cell granulomas. (3) Hyperactive humoral immunity is probably the result of removal of T suppressor activity. There is an increased number of B lymphocytes in the peripheral blood, and most patients have hyperimmunoglobulinemia.
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The hallmark of sarcoidosis is the presence of small, noncaseating epithelioid cell granulomas (Figure 35-12). The granulomas contain Langhans-type giant cells and are associated with fibrosis. Several types of inclusions may be present, but although characteristic of sarcoidosis they are not pathognomonic. Schaumann (conchoidal) bodies are round, calcified, laminated bodies in the cytoplasm of giant cells. Asteroid bodies are smaller and have a central pink zone surrounded by a clear halo that is traversed by fine radial pink lines.
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In the lung, granulomas are found in the alveolar septa (Figure 35-12) and along the pulmonary lymphatics in the bronchial wall. Granulomas are associated with interstitial inflammation and fibrosis. Chronic disease progresses to end-stage honeycomb lung. Granulomas may also be found in lymph nodes, liver, spleen, skin, and many other organs.
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The diagnosis of sarcoidosis is made on clinical grounds. A finding of noncaseating epithelioid granulomas on histologic examination of biopsies provides confirmatory evidence when cultures of these tissues do not grow out mycobacteria and fungi. The cells in the granuloma release angiotensin-converting enzyme into the serum; the detection of elevated levels of this enzyme in serum (seen in 60% of patients) is a useful test for sarcoidosis. High serum levels of angiotensin-converting enzyme indicate activity of sarcoidosis and, when present, provide an important method of monitoring the course of disease.
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In the United States, sarcoidosis occurs 10 times more frequently in blacks than in whites. Women are more commonly affected, and the most common age at onset is between 20 and 35 years. In Europe, sarcoidosis is more common in the Scandinavian countries.
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An abnormality in the chest x-ray is present in over 90% of patients with sarcoidosis. Bilateral hilar lymphadenopathy is the most common finding. Pulmonary infiltrates due to interstitial pneumonitis may also be present.
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Sarcoidosis has a variable course. About 65% of patients with hilar adenopathy alone undergo spontaneous remission. Pulmonary parenchymal involvement usually signifies progressive chronic disease. Disability and death from pulmonary fibrosis occur in a minority of patients. Steroids are effective in controlling the disease and are indicated when there is symptomatic lung involvement, ocular lesions, cardiac disease, or neurologic disease.
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Wegener's Granulomatosis
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Wegener's granulomatosis is a disease of unknown cause, although a hypersensitivity reaction to an unknown antigen has been postulated. Anti-neutrophil cytoplasmic autoantibodies (ANCA) are present in more than 95% of patients with Wegener's granulomatosis. ANCAs are not specific, however, as they are also found in polyarteritis nodosa. There are two distinct immunofluorescence patterns of ANCA: (1) diffuse cytoplasmic ANCA (c-ANCA) and (2) perinuclear ANCA (p-ANCA). The pattern of c-ANCA is more specific for Wegener's granulomatosis than p-ANCA. The way these autoantibodies are related to the pathologic lesion is unknown. Wegener's granulomatosis is characterized by necrotizing vasculitis of small arteries. The inflammatory reaction around the affected vessel is granulomatous, with scattered neutrophils, eosinophils, and lymphocytes.
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The classic form of the disease involves (1) the nose, paranasal sinuses, and nasopharynx; (2) the lungs; and (3) the kidneys. Variants with involvement of other organs or sparing of one or two of the classic sites also occur.
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Pulmonary involvement is characterized by a rapidly expanding infiltrate that tends to be bilateral, with multiple nodular mass lesions that tend to cavitate. The renal disease is a necrotizing glomerulitis that frequently progresses to crescentic glomerulonephritis and renal failure. Nasal lesions are usually ulcerating granulomas.
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Clinical progression is rapid, with death from either the renal or pulmonary lesions in the majority of cases. Immunosuppressive drugs such as cyclophosphamide have prolonged survival.
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Lymphomatoid Granulomatosis
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Lymphomatoid granulomatosis is a poorly defined entity of uncertain cause. It is a systemic disorder affecting the lung, nervous system, kidney, skin, and many other organs. Histologically, there are necro-tizing granulomas in the lung that are infiltrated by atypical lymphocytes resembling immunoblasts. Lymphomatoid granulomatosis is a premalignant lesion with a high risk for pulmonary malignant lymphoma; some authorities hold that the process is an indolent form of malignant lymphoma from the outset. The prognosis is poor.
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Bronchocentric Granulomatosis
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Bronchocentric granulomatosis is a disease of uncertain cause characterized by granulomatous inflammation centered around the airways. The walls of the airways are destroyed, and their lumens are filled with necrotic material. No infectious agent can be isolated. Patients present with dyspnea, wheezing, and the consequences of bronchial obstruction such as pneumonia, lung abscess, and bronchiectasis.
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Pulmonary Alveolarproteinosis
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Although traditionally included with infiltrative lung diseases, pulmonary alveolar proteinosis is neither an interstitial pneumonitis nor is it associated with fibrosis. It is characterized by filling of the alveolar spaces with a homogeneous, proteinaceous, lipid-rich material thought to be composed of surfactant and cellular debris. Few or no inflammatory cells are present.
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The cause is unknown. Increased production or decreased clearance of surfactant has been suggested as the cause.
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Patients with alveolar proteinosis present with dyspnea and dry cough. The chest x-ray shows consolidation first affecting the lung bases. The infiltrates have a typical ground-glass appearance on chest x-ray. Hypoxemia is common and often severe.
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While a few deaths have been reported, alveolar proteinosis is usually a benign disease, with most patients undergoing spontaneous remission. There is a good clinical response to treatment with pulmonary lavage.