Silicosis

INTRODUCTION — Silicosis refers to a spectrum of pulmonary diseases caused by inhalation of free crystalline silica (silicon dioxide). The written record of occupational lung disease caused by silica inhalation extends back to ancient Egypt and Greece. Despite a clear understanding of how to prevent this disease, new cases of silicosis continue to occur [1-6].

The clinical presentations, diagnostic evaluation, and treatment of silicosis will be reviewed here. The imaging of occupational lung disease and the evaluation of pulmonary disability are discussed separately. (See "Imaging of occupational lung diseases" and "Evaluation of pulmonary disability".)

DEFINITIONS — Several clinical presentations of disease have been described:

●Acute silicosis – Acute silicosis, also known as acute silicoproteinosis, develops after exposure to high concentrations of respirable crystalline silica and results in symptoms within a few weeks to a few years after the initial exposure.

●Chronic silicosis – Chronic silicosis usually has the radiographic pattern described below as simple silicosis. In a minority of those with chronic disease, nodules coalesce resulting in progressive massive fibrosis (PMF).

•Simple silicosis – Simple silicosis is characterized radiographically by innumerable, sharply marginated, small rounded opacities composed of hyalinized, collagenous nodules, with a predilection for dorsal aspects of the upper lobes.

•Progressive massive fibrosis – PMF, also known as complicated or conglomerate silicosis, is characterized by nodular lung lesions 1 cm or greater in diameter that have radiating strands extending out from the nodule. These nodules can contain air bronchograms and calcifications. The lesions of PMF occur predominantly in the upper lung zones of the chest radiograph.

●Accelerated silicosis – Accelerated silicosis is associated with high-level exposure to silica and develops within 5 to 10 years of initial exposure. Imaging features of accelerated silicosis overlap with both acute and chronic silicosis, with ground glass opacities suggesting silicoproteinosis in combination with silicotic nodules and interstitial fibrosis characteristic of more chronic disease [7].

EPIDEMIOLOGY — Workers in a broad range of industries are exposed to crystalline silica (table 1) [4,8-11]. Up to 200,000 miners and 1.7 million non-mining workers in the United States have experienced significant occupational exposure to inhaled silica, and new cases of silicosis are recognized worldwide every year [12-14].

The overall mortality attributable to silicosis has decreased substantially in the United States over the past 50 years, largely because of improved workplace protections [15,16]. From 1968 to 2002, the number of silicosis deaths decreased from 1157 (8.91 per million persons aged ≥15 years) to 148 (0.66 per million), corresponding to a 93 percent decline in the overall mortality rate [15]. This gradual decrease has continued; the United States Centers for Disease Control and Prevention reported a decline from 164 (0.74 per million persons aged ≥15 years) in 2001 to 101 (0.39 per million persons aged ≥15 years) in 2010 [17].

Worldwide, silicosis mortality declined from an estimated 15,107 (2.8 per million) in 1990 to 12,887 (1.7 per million) in 2019 [18]. The 2019 age-standardized mortality burden was highest in Palau (6 per million), North Korea (5.9 per million), Chile (5.1 per million), China (4 per million), and Portugal (3.7 per million).

Among hard rock miners, radiographic evidence of silicosis is present in approximately one-third. The rate of positive chest radiographs correlates at least in part with the degree of dust exposure, although other factors such as race may play a role. Black workers in the United States have a two to seven times higher rate of developing silicosis compared with White workers with the same dust exposure [19].

FORMS OF SILICA AND MECHANISM OF TOXICITY — Silica (silicon dioxide) is the most abundant mineral on earth. Silica exists in both crystalline and amorphous forms. Amorphous forms, including vitreous silica and diatomite (formed from skeletons of prehistoric marine organisms), are relatively nontoxic after inhalation [20]. In contrast, inhaled crystalline silica (quartz, cristobalite, and tridymite) is associated with a spectrum of pulmonary diseases.

Quartz is the most common type of crystalline silica and is a major component of rocks including granite, slate, and sandstone. Granite contains about 30 percent free silica, slate about 40 percent, and sandstone is almost pure silica [21]. Cristobalite and tridymite occur naturally in lava and are formed when quartz or amorphous silica is subjected to very high temperatures.

The toxicity of crystalline silica appears to result from the ability of crystalline silica surfaces to interact with aqueous media, to generate oxygen radicals, and to injure target pulmonary cells such as alveolar macrophages. Resultant generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells lead to cytokine networking between inflammatory cells and resident pulmonary cells, resulting in inflammation and fibrosis [22].

"Free" crystalline silica is unbound to other minerals. "Combined" forms of silica, called silicates, are compounds in which silica is bound to other minerals. Examples of silicates used in industry include asbestos (hydrated magnesium silicate), talc (Mg3Si4O10(OH)2), and kaolinite (Al2Si2O5(OH)4), a major component of kaolin (china clay) [23]. The pulmonary effects of asbestos inhalation are substantial, and are discussed separately. (See "Asbestos-related pleuropulmonary disease".)

SILICA IN THE WORK ENVIRONMENT — Any occupation that disturbs the earth's crust or involves processing or using silica-containing rock or ores has potential risk for silicosis. The history of occupational exposure to silica should include the types and duration of employment (table 1), dust levels, and use of effective respiratory protection. Determining whether the worker's occupational silica exposure is sufficient to cause silicosis can be difficult. Silicosis can occur in many industries and work settings including mining, quarrying, sandblasting, masonry, stone cutting, foundry work, and ceramics. Occupations that involve crushing or grinding of quartz-containing materials are also hazardous.

Current workplace exposure limits in the US are not fully protective of all exposed workers. (See "Evaluation of pulmonary disability", section on 'History and physical examination'.)

●Mining and hydraulic fracturing – Underground mining for coal or metal can cause silicosis, particularly when tunneling through rock with high silica content or when using sand as a friction material on rails [24-27]. Although dust exposure levels are generally lower in surface and strip mines, silicosis also occurs in these settings, particularly among drillers and their assistants [28,29]. Exposure to respirable silica has also been described in hydraulic fracturing for oil and gas recovery [30].

●Sandblasting – Sandblasting generates respirable aerosols of silica and is associated with an especially increased risk for silicosis [31-34]. The very high risk associated with sandblasting may be due to generation of freshly fractured silica particles, which appear to be particularly toxic [35]. High rates of silicosis have also been described in Turkish workers using silica to sandblast denim [34,36]. The United Kingdom restricted use of abrasives containing silica in 1949, and other European countries abandoned sandblasting during the 1960s. In contrast, there are no special restrictions on the use of sand for abrasive blasting in the United States, except in the underground mine environment [37].

●Foundry work – Foundry workers can have significant exposure to aerosolized silica [38,39]. In foundries, metal castings are made by pouring molten metal into molds. These molds generally contain finely milled quartz sands, and exposure to respirable crystalline silica aerosols occurs both when the mold is knocked off the cast and when the cast is cleaned or polished. These aerosols often contain cristobalite, which is formed as a result of the intense heat associated with producing casts and is particularly toxic.

●Masonry – Production of silica flour, sand, concrete, and silica-based ceramics are also associated with an increased risk of silicosis [4,40-43].

●Natural and artificial stone cutting – Both natural and artificial stone (also referred to as engineered, agglomerated, or reconstituted stone) used in fabrication of countertops generate respirable crystalline silica during cutting and grinding. The silica content in artificial stone is typically greater than 90 percent, potentially exposing workers to higher concentrations of silica dust [44]. Exposures are often intense and lead to severe forms of silicosis [43,45,46]. Engineered stone countertops have become increasingly popular, and outbreaks of silicosis in stone fabrication workers have been reported worldwide [45-50]. A large case series of 52 stone fabrication workers with silicosis in California has further underscored the need for identification of at-risk workers and implementation of workplace exposure controls [51,52]. Among over 1000 stonemasons exposed to engineered stone who underwent systematic medical surveillance in Queensland, Australia between 2018 and 2021, nearly 22 percent demonstrated evidence of silicosis and 3 percent showed progressive massive fibrosis [53], suggesting that silica-related disease is dramatically underdiagnosed within this burgeoning industry [52,54].

●Other settings – The short list of high-risk industries specifically noted above is not complete, as silicosis can occur in many dusty settings, even ones where risk was not previously appreciated (table 1). As an example, nine cases of silicosis were confirmed among dental laboratory technicians in the United States between 1994 and 2000 [8]. Other occupations (eg, agriculture, highway repair) in which the soil is disturbed can lead to significant exposures to respirable silica in airborne soil [4,41,55,56]. Although occupation is the major risk factor for silicosis, rare cases have been reported of chronic silicosis after environmental exposures in regions where soil silica content is high and dust storms are common [57].

ACUTE SILICOSIS — Acute silicosis, also known as acute silicoproteinosis, develops after exposure to high concentrations of respirable crystalline silica and results in symptoms within a few weeks to a few years after the initial exposure [3,58-63]. Acute silicosis is rare; most individuals with extremely high silica exposures initially display radiographic features identical to those of simple silicosis, which progress to progressive massive fibrosis (PMF) over a period of as few as four to five years [58,61]. The reason that some individuals develop acute silicosis while others develop accelerated silicosis after overwhelming silica exposure is not known; genetic factors may play a role [6,64,65]. (See 'Accelerated silicosis' below.)

Clinical presentation — Acute silicosis is characterized by rapid onset of symptoms including dyspnea, cough, weight loss, fatigue, and sometimes pleuritic pain and fever [66]. These symptoms may precede significant radiologic findings. On physical examination, crackles are usually present.

Evaluation — When acute silicosis is suspected due to the onset of cough, dyspnea, and sometimes fever or pleuritic chest pain in a patient with high dose exposure to silica in the recent past (eg, months to a few years), the evaluation is aimed at documenting the exposure history and excluding other processes in the differential diagnosis, such as pneumonia, acute respiratory distress syndrome, heart failure, diffuse alveolar hemorrhage, eosinophilic pneumonia, lipoid pneumonia, and pulmonary alveolar proteinosis. (See 'Silica in the work environment' above.)

Laboratory — There are no laboratory tests for the diagnosis of acute silicoproteinosis. However, a complete blood count and differential, brain natriuretic peptide, granulocyte macrophage-colony stimulating factor (GM-CSF) antibodies, and cultures of blood and sputum are helpful in excluding other disease processes in the differential diagnosis.

Assessment of oxygenation is important, either with pulse oxygen saturation or arterial blood gas, to determine the severity of respiratory impairment and whether the patient will be able to tolerate diagnostic procedures.

Pulmonary function — Lung function in the setting of acute silicosis shows spirometric reduction of forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) [63]. While few studies report lung volume and diffusion capacity measurements, both typically are reduced [50,58].

Imaging — In acute silicosis, the chest radiograph demonstrates characteristic bilateral, diffuse ground glass opacities (image 1) [58,67,68]. The opacities may be perihilar or basilar [69]. These features may progress from a pattern of lower zone opacities to large masses of coalesced parenchymal tissue in the mid and lower zones, which are typically bilateral but not always symmetrical [58,69]. (See "Imaging of occupational lung diseases", section on 'Silicosis'.)

The high-resolution computed tomography (HRCT) findings consist of numerous bilateral centrilobular nodular opacities, focal ground glass opacities, and patchy areas of consolidation [70]. In a small series that compared pulmonary alveolar proteinosis (PAP) and acute silicosis, the most common HRCT finding in PAP was “crazy paving”, while the most common finding in acute silicosis was dependent consolidation and nodular calcification [71]. (See "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults".)

Hilar lymph node enlargement may be apparent on HRCT, which is a typical feature of silicosis, but not of PAP [69]. In a series of 13 patients, calcified lymph nodes were noted on HRCT in 11 (85 percent) [70]. (See "Imaging of occupational lung diseases", section on 'Silicosis'.)

Bronchoalveolar lavage — When acute silicosis is suspected, bronchoalveolar lavage (BAL) is used to exclude infection, eosinophilic pneumonia, and alveolar hemorrhage. In acute silicoproteinosis, BAL yields a thick, opaque (milky) effluent similar to that seen in pulmonary alveolar proteinosis. On cytologic examination, the macrophages in the BAL are foamy and the lipoproteinaceous material stains brightly positive with periodic acid-Schiff (PAS) reagent [72]. (See "Basic principles and technique of bronchoalveolar lavage".)

Lung biopsy and histopathology — A lung biopsy is not necessary in the setting of a definite exposure history and characteristic radiographic findings. When tissue is obtained, the histopathology of acute silicosis is different from that of chronic or accelerated silicosis. Silicotic nodules are rarely seen, and, if present, are usually poorly developed. As described for BAL fluid, proteinaceous material fills the alveoli and consists largely of phospholipids or surfactant (or surfactant-like material) and stains with PAS reagent. The interstitium is thickened with inflammatory cells; a minimal amount of pulmonary fibrosis is typically present. Alveoli may be lined with prominent epithelial cells, the majority of which are hypertrophic type II pneumocytes [73]. In addition, desquamated pneumocytes, macrophages, and silica particles are found in the alveolar spaces. The histologic appearance of acute silicosis resembles that of idiopathic alveolar proteinosis (picture 1) [60]. (See "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults".)

Diagnosis — The diagnosis of acute silicosis is based upon the history of acute, high dose silica exposure, imaging findings of diffuse nodular and patchy consolidative opacities (image 1), a milky, lipoproteinaceous bronchoalveolar lavage effluent, and exclusion of other potential explanations (infection, pulmonary edema, alveolar hemorrhage, eosinophilic pneumonia, primary pulmonary alveolar proteinosis). A lung biopsy is not necessary in the setting of a definite exposure history and these characteristic findings.

Once lipoproteinaceous fluid has been obtained by BAL or observed on biopsy, other causes of alveolar proteinosis or lipidosis should be evaluated: an occupational history can identify inhalational exposure to agents such as titanium, indium-tin oxide, or aluminum; serum tests for GM-CSF antibodies can confirm autoimmune pulmonary alveolar proteinosis (PAP); microbiologic stains and/or cultures of samples obtained from bronchoscopy can diagnose infectious agents such as Pneumocystis jirovecii or Nocardia; and the presence of leukemic cells in the peripheral blood are a clue to secondary PAP. (See "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis" and "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults", section on 'Diagnostic evaluation' and "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV", section on 'Establishing the diagnosis'.)

Treatment — Acute silicosis is typically progressive and no specific therapy has been identified. Thus, the main treatments for acute silicosis are complete avoidance of further exposure and supportive care. (See 'Treatment' below.)

The poor prognosis has spurred attempts at experimental therapy, and benefit has been reported in isolated cases with systemic glucocorticoids and whole lung lavage, but formal evaluation of these interventions has not been performed.

●In one case report, intravenous glucocorticoid therapy followed by oral prednisone was associated with initial improvement in the chest radiograph and pulmonary function [66]. However, two years after the initial improvement, the patient developed PMF. (See 'Definitions' above.)

●Whole lung lavage has been attempted, based on the similarity of acute silicosis and PAP [68,74,75]. While the procedure is well-tolerated in PAP, its clinical utility in silicoproteinosis is unclear. In one case report, whole lung lavage was administered to a patient with acute silicosis and hypoxemic respiratory failure requiring mechanical ventilation, after empiric antibiotics and systemic glucocorticoid therapy were unsuccessful [68]. Following two sessions of whole lung lavage under general anesthesia, the patient was extubated and discharged from the hospital. The technique of whole lung lavage is described separately. (See "Treatment and prognosis of pulmonary alveolar proteinosis in adults", section on 'Whole lung lavage'.)

Lung transplantation is a potential option for patients with progressive respiratory failure. (See 'Treatment' below.)

Prognosis — The prognosis of patients with acute silicosis is very poor [69,70]. Patients rapidly develop cyanosis, cor pulmonale, and respiratory failure. Survival after onset of symptoms is typically less than four years; mycobacterial and fungal infections may complicate the clinical course.

CHRONIC SILICOSIS — Chronic silicosis (includes simple silicosis and progressive massive fibrosis [PMF]) develops slowly, usually appearing 10 to 30 years after first exposure. It is not uncommon for the radiographic appearance of silicosis to occur many years after cessation of employment in a job associated with exposure [76]. The progressive coalescence of silicotic nodules leads to replacement of upper lobe parenchyma by the nodules and air trapping and emphysema in the lower lobes due to fibrotic retraction of the upper lobes with resultant respiratory impairment.

Clinical manifestations — The clinical presentation of chronic silicosis is variable. Individuals with simple silicosis may be asymptomatic with the only manifestation being an abnormal chest radiograph. When symptoms are present, chronic cough and dyspnea on exertion are common and become more frequent and severe with worsening radiographic abnormalities [19,77,78]. Among workers with chronic exposure to respirable silica, approximately 35 percent will report cough and sputum production [19]. Some of these workers will have chronic bronchitis due to silica inhalation, although cigarette smoking may be contributory.

PMF is associated with more severe symptoms of cough and dyspnea than simple silicosis.

Physical examination of the chest is often unremarkable in simple silicosis, although a variety of abnormal breath sounds, including fine crackles, coarse crackles (often at end inspiration), rhonchi, and/or wheezes, have been reported to occur in approximately 25 percent of affected individuals [79].

Patients with PMF frequently have decreased breath sounds and may have inspiratory crackles. PMF is not specifically associated with digital clubbing and, if present, another etiology should be sought. Other signs of chronic respiratory failure and cor pulmonale may be present.

Evaluation — When chronic silicosis is suspected due to the onset of respiratory symptoms (eg, dyspnea, productive cough) or typical chest imaging findings, the evaluation is aimed at confirming the exposure history, assessing the degree of respiratory impairment, and excluding other causes. A careful occupational history is essential, as described above. (See 'Silica in the work environment' above.)

Laboratory testing — There are no laboratory tests for the diagnosis of chronic silicosis. As mycobacterial infection is often in the differential diagnosis or may develop as a complication, testing for latent tuberculosis via skin test or interferon release assay is often obtained. In addition, sputum smear and culture for mycobacteria are obtained in the presence of fever, weight loss, hemoptysis, or complicated silicosis on radiographic imaging. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)

Pulmonary function — Pulmonary function tests (PFTs) are a key component in the evaluation of respiratory symptoms and abnormal radiographic findings. Typically, spirometry before and after bronchodilator, lung volumes, diffusing capacity for carbon monoxide (DLCO), and resting pulse oxygen saturation are obtained. (See "Approach to the patient with dyspnea" and "Overview of pulmonary function testing in adults".)

Complete cardiopulmonary exercise testing may be helpful in evaluating patients with respiratory symptoms, particularly exertional dyspnea, who have a history of exposure to silica and whose resting lung function is normal. (See "Cardiopulmonary exercise testing in cardiovascular disease".)

Workers exposed to respirable crystalline silica may have normal spirometry or may develop a range of pulmonary function test abnormalities [78,80-82]. In a study of 1028 foundry workers without chest radiograph abnormalities, there was a 1.1 mL per year decline in forced expiratory volume in one second (FEV₁) for each mg per cubic meter (mg/m³) of mean silica exposure [80]. The presence of even mild radiographic findings of chronic or accelerated silicosis is associated, on average, with a greater degree of abnormality in pulmonary function. Spirometry shows a mixed picture of obstructive and restrictive ventilatory impairment with decreased FEV₁ and FEV₁/forced vital capacity (FVC) ratio [77]. (See "Overview of pulmonary function testing in adults".)

Pulmonary function, on average, worsens in association with worsening radiographic abnormalities of chronic or accelerated silicosis; cigarette smoking is often contributory [83]. PMF is associated with the worst pulmonary function abnormalities, including decreased compliance, decreased FEV₁ and FEV₁/FVC ratio, and decreased DLCO [77,84]. In a number of studies using chest CT scan to evaluate lung parenchyma in chronic or accelerated silicosis, lung function abnormalities correlated better with the emphysematous changes of silicosis than the nodular changes of silicosis [85-87].

Imaging — A chest radiograph is obtained in virtually all patients undergoing evaluation for chronic silicosis; high resolution computed tomography (HRCT) is helpful for patients with an atypical clinical presentation or atypical findings on chest radiograph. In our occupational lung disease specialty clinic, we often obtain a baseline HRCT scan in patients with radiographic findings of silicosis to document the presence and extent of nodules, emphysema, and other silica-related abnormalities that may progress in the future.

●Chest radiograph – The typical chest radiograph finding in chronic simple silicosis is the presence of innumerable, small, rounded opacities (less than 10 mm in diameter). The nodules are generally rounded but can be irregular, and are distributed predominantly in the upper lung zones (image 2A-B). Progressive massive fibrosis (PMF, also known as conglomerate silicosis) occurs when these small opacities gradually enlarge and coalesce to form larger, upper- or mid-zone opacities more than 10 mm in diameter (image 3) [24]. As these opacities progressively enlarge, the hila are retracted upward in association with upper lobe fibrosis and lower lobe hyperinflation. The opacities of PMF can be asymmetrical, and may mimic a neoplastic process. Cavitation may also be present in advanced disease or in the setting of mycobacterial superinfection. Hilar adenopathy with prominent calcification is present in up to 5 percent of workers with silicosis. (See "Imaging of occupational lung diseases", section on 'Silicosis'.)

Several reports have compared the accuracy of the chest radiograph appearance to pathologic examination of the lungs at autopsy in detecting silicosis. In a study of more than 500 South African gold miners, when radiographs were scored using the International Labor Office (ILO) classification system profusion classes of 1/0, 1/1, and 1/2 as cutoffs, sensitivities were found to be 50, 37, and 25 percent, respectively, and specificities 89, 96, and 100 percent, respectively [88]. A subsequent smaller study of 241 South African gold miners evaluated use of "miniradiographs" with cutoffs at ILO profusion categories 0/1, 1/0, and 1/1. Sensitivities were 89, 74, and 71 percent, respectively, and specificities were 73, 87, and 96 percent, respectively [89]. Reasons for improved sensitivity in the second study were unclear. (See "Imaging of occupational lung diseases", section on 'The International Labor Office classification' and "Evaluation of diffuse lung disease by conventional chest radiography".)

●High-resolution computed tomography – HRCT is usually not necessary in simple silicosis unless atypical clinical or radiographic features are noted (eg, fever, spiculated nodules, a single nodule of substantially larger size than the others). However, HRCT has been shown to improve sensitivity and significantly reduce inter-reader variability compared with conventional radiography [90,91]. The typical HRCT findings in simple silicosis are bilateral, symmetric, centrilobular, and perilymphatic nodules with sharp margination (image 4). These nodules calcify in 10 to 20 percent of patients.

HRCT is superior to conventional chest radiography for documentation of conglomerate lesions and emphysematous changes associated with complicated silicosis (image 5) [84-87,92-94]. (See "High resolution computed tomography of the lungs".)

Although pleural effusions are unusual, pleural thickening appears to be common, especially among patients with more severe disease. In a series of 110 patients with biopsy proven silicosis followed for a mean of 14 years, pleural effusions were noted in 12 patients (11 percent), but pleural thickening was present in 64 patients (58 percent) [95].

●FDG-PET scan – Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) scans are often used to help differentiate benign from malignant lung lesions. However, FDG-PET uptake can be increased in PMF in the absence of malignancy or infection [96]. While the ideal cut-off for maximum standardized uptake value (SUV_max) has not been agreed upon, using a threshold of 7.4, may help differentiate PMF from lung cancer in patients with pneumoconiosis. The SUV_max, short and long axis diameters, and Hounsfield units of lung masses on FDG-PET scans were evaluated in a series of 49 patients with pneumoconiosis and a total of 83 lung masses, 42 of which were lung cancer [97]. The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of lung cancer were 81 percent, 73 percent, and 77 percent, respectively, with an SUV cut-off of 7.4. Metastatic lymph nodes also showed a higher SUV_max than benign lesions. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer".)

Bronchoscopy — Flexible bronchoscopy has a limited diagnostic role in chronic silicosis, and, for most patients, bronchoscopy to confirm the diagnosis is not indicated. However, bronchoscopic washings, brushing, or bronchoalveolar lavage may be used to obtain samples for microbiologic studies and cytology when infection and/or malignancy are in the differential diagnosis based on the imaging results. In general, transbronchial biopsy is avoided in chronic silicosis due to the presumed risk for pneumothorax and the small tissue sample size. (See "Role of lung biopsy in the diagnosis of interstitial lung disease".)

Diagnosis — In general, the diagnosis of chronic silicosis is a clinical diagnosis; lung biopsy to obtain a histopathologic diagnosis is reserved for situations when a confident clinical diagnosis cannot be made.

Clinical diagnosis — A clinical diagnosis of chronic silicosis is based on three key elements:

●A history of silica exposure sufficient to cause the degree of illness and the appropriate latency from the time of first exposure (see 'Silica in the work environment' above)

●Chest imaging (usually a conventional chest radiograph) that shows opacities consistent with silicosis [98] (see 'Imaging' above)

●Absence of another diagnosis more likely to be responsible for the observed abnormalities

When the three clinical requirements for the diagnosis of silicosis are met, additional evaluation is not necessary to make the diagnosis.

Lung biopsy — In rare instances, the diagnosis of chronic silicosis cannot be made clinically, and biopsy of the lung is necessary. The traditional view has been that a surgical lung biopsy (via video-assisted thoracoscopy or thoracotomy) is preferred due to the chance of pneumothorax after transbronchial lung biopsy. The increased risk for pneumothoraces in silicosis may be explained by the presence of stiff upper zones while emphysematous changes are present in the lower zones. The advantages and disadvantages of transbronchial and surgical approaches to lung biopsy are discussed separately. (See "Role of lung biopsy in the diagnosis of interstitial lung disease".)

Pathology — The earliest histopathologic changes identifiable in workers with chronic low-level exposure to free crystalline silica are dust-laden macrophages and loose reticulin fibers in the peribronchial, perivascular, and paraseptal or subpleural areas [22,99]. With long-term exposure, silicotic nodules, the pathologic hallmark of silicosis, develop a characteristic layered or spiral appearance. The central zone is hyalinized and composed of concentrically arranged collagen fibers. The peripheral zone is whorled and becomes less organized toward the edges. This outer zone contains macrophages, lymphocytes, and lesser amounts of loosely formed collagen and is the site of active inflammation and enlargement.

While not always present, silica particles typically are birefringent under polarized light; they may be present intra- or extracellularly [6]. Energy dispersive X-ray analysis (EDXRA) of metal content is rarely used due to very limited availability.

Silicosis in hilar lymph nodes may precede parenchymal silicosis, and lymph node fibrosis may impair silica clearance and contribute to development of parenchymal fibrosis [100]. As the disease progresses, the periphery of the silicotic nodule moves farther from the hyalinized center, enmeshing small airways, pleura, and blood and lymphatic vessels in the fibrotic process (picture 2). Coalescence of silicotic nodules forms the PMF lesion. As these aggregates enlarge, the center of the PMF lesions may undergo ischemic necrosis and cavitate. Superimposed mycobacterial infection can also lead to cavitation.

Differential diagnosis — Diseases capable of mimicking the radiographic appearance of silicosis include infections (eg, mycobacterial or fungal disease), pulmonary malignancy (a consideration when the coalesced lesions of progressive massive fibrosis are unilateral or asymmetric), rheumatoid nodules (referred to as Caplan's Syndrome in the presence of coal workers’ pneumoconiosis [101]), sarcoidosis, and pulmonary Langerhans cell histiocytosis. (See "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Imaging of occupational lung diseases", section on 'Silicosis' and "Imaging of occupational lung diseases", section on 'Coal worker's pneumoconiosis' and "Pulmonary Langerhans cell histiocytosis" and "Diagnostic evaluation of the incidental pulmonary nodule".)

Treatment — There is no proven specific therapy for chronic silicosis. All patients with radiographic evidence of silicosis should avoid further exposure to respirable silica, which may include optimizing respiratory protection in the workplace or changing their occupation.

Supportive therapy includes smoking cessation (if needed), treatment of airflow limitation with bronchodilators, vaccination against influenza and pneumococcus, and use of supplemental oxygen (if indicated) to prevent complications of chronic hypoxemia. (See "Overview of smoking cessation management in adults" and "Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults" and "Long-term supplemental oxygen therapy".)

Systemic glucocorticoid therapy has been used in an attempt to interrupt the inflammation that leads to progressive silicosis, but no large, randomized clinical trials have been performed. We do not advise using glucocorticoids for chronic silicosis in the absence of another indication, such as a flare of chronic obstructive pulmonary disease (COPD). The evidence in favor of glucocorticoid therapy comes from an observational study, in which prednisolone was administered to 34 patients with chronic silicosis [102]. Treatment resulted in statistically (although not clinically) significant improvements in lung volumes, carbon monoxide diffusing capacity, and partial pressure of arterial oxygen.

Patients should be referred for appropriate counseling concerning benefits, such as worker's compensation, to which they may be entitled. (See "Evaluation of pulmonary disability".)

Lung transplantation — Successful lung transplantation has been reported in advanced silicosis [103-107]. In a series of 19 patients with silicosis who underwent lung transplantation, the six-month, one-year, and three-year survivals were 86, 86, and 76 percent [105]. (See "Lung transplantation: An overview" and "Lung transplantation: General guidelines for recipient selection".)

Experimental treatments — A number of experimental treatments for chronic silicosis have been proposed, including inhibition of cytokines (eg, interleukin-1, tumor necrosis factor alpha), antioxidant therapy, and intratracheal administration of bone marrow-derived mononuclear cells [22,108,109]. Parenteral administration of a polymer, polyvinyl pyridine N-oxide (PVNO), inhalation of aluminum, and administration of tetrandrine, an active component of the Chinese traditional medicine "han fang ji" have not proven useful [22,110-116]. Concerns about potential adverse consequences of such treatments have been expressed. The role of antifibrotic agents such as nintedanib and pirfenidone in patients with progressive silicosis awaits further study [117,118].

Prognosis — Mortality from silicosis in the United States declined from 8.91 deaths per million to 0.66 in the period from 1968 to 2002 [15]. While the number of deaths from silicosis overall has declined since 1968, the number of silicosis-associated deaths reported among persons aged 15 to 44 did not decline substantially prior to 1995 [119]. It is not known to what extent deaths among younger workers were caused by acute or accelerated forms of silicosis.

Silicosis-related deaths among workers of all ages are associated with significant premature mortality [120]. Between 1996 and 2005, 1746 deaths due to silica exposure resulted in 20,234 years of life lost from life expectancy, with an average of 11.6 years of life lost. For the same period, among 307 decedents who died before age 65, or the end of a working life, there were 3045 years of life lost to age 65, with an average of 9.9 years of life lost from a working life [121].

Exposure intensity along with specific industry and job duties are associated with prognosis. For example, among 145 former denim sandblasters with early silicosis (defined as a category 1/0 small opacity profusion on chest radiograph), follow-up four years later showed that radiographic progression had occurred in 82 percent, associated with significant decline in pulmonary function in 66 percent [122].

ACCELERATED SILICOSIS — Accelerated silicosis is associated with high-level exposure to silica and develops within 10 years following first exposure. It is differentiated from chronic silicosis by its more rapid development and by imaging features that may overlap with both acute and chronic disease. Outbreaks of accelerated (as well as acute and chronic) silicosis in denim sandblasters, Appalachian coal miners, and artificial stone workers have shown rapidly progressive and severe disease [48,122].

The clinical presentation of accelerated silicosis is variable. Affected individuals may be asymptomatic with the only manifestation being an abnormal chest radiograph. Among symptomatic patients, chronic cough and dyspnea on exertion are common and become more frequent and severe with worsening radiographic abnormalities [77].

Physical examination of the chest is usually unremarkable, although a variety of abnormal breath sounds, including fine crackles, coarse crackles (often at end inspiration), rhonchi, and/or wheezes, have been reported to occur in a substantial proportion of affected individuals [79].

The diagnosis is based on the history of high-level silica exposure for <10 years and imaging features that may overlap with acute and chronic silicosis. (See 'Imaging' above.)

The approach to treatment is the same as for chronic silicosis described above and includes avoidance of silica exposure, smoking cessation, bronchodilators if airflow limitation is present on spirometry, vaccination against influenza and pneumococcus, and supplemental oxygen if needed. (See 'Treatment' above.)

Systemic glucocorticoid therapy has occasionally been associated with transient improvement in symptoms, but this observation has not been examined in randomized trials.

Patients with accelerated silicosis are at increased risk for the later development of progressive massive fibrosis, a form of chronic silicosis, and may be at greater risk of complications [26]. (See 'Chronic silicosis' above and 'Complications' below.)

COMPLICATIONS — Silicosis is associated with an increased risk of mycobacterial infection, chronic necrotizing aspergillosis, lung cancer, rheumatic disorders, kidney disease, chronic airflow obstruction, and chronic bronchitis [2,123].

Mycobacterial infection — Mycobacterial infection, particularly tuberculosis (TB), is a long recognized and well-established complication of silicosis and should always be suspected when a patient with silicosis develops constitutional symptoms, worsening respiratory impairment, hemoptysis, or changes in the chest radiograph [124-130]. Cavitation of a progressive massive fibrosis (PMF) lesion is a particularly concerning finding (image 6). Risk factors and specific mechanisms for mycobacterial lung infection in silica-exposed workers are not well understood, though underlying HIV infection, previous TB, cumulative years of respirable crystalline silica (RCS) exposure, and more intense exposures increase risk [131].

It is important to evaluate for active TB using microbiologic techniques (eg, smear and culture of sputum, bronchial washings), since silicosis can mask the radiographic changes of active TB. In addition, the risk of active TB in patients with silicosis and a positive purified protein derivative (PPD) is markedly increased. (See "Diagnosis of pulmonary tuberculosis in adults".)

Active TB should be treated with multiple antituberculous drugs. Some reports indicate that short course multidrug treatment of latent TB infection may not be effective in the presence of silicosis [132]. Older studies suggested that antituberculous chemotherapy should be given for an extended period, ranging from more than a year to a lifetime [133]. However, other studies have shown successful outcomes and acceptable relapse rates with shorter treatment regimens of five and nine months [134,135]. The largest study found a lower relapse rate when the usual multidrug regimen was given for eight months instead of six [136]. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

It has been recommended that patients with established silicosis, or those with prolonged exposure to inhaled crystalline silica, undergo tuberculin skin testing using PPD. A PPD reaction ≥10 mm is considered positive in this population. Latent TB infection should be treated in accordance with established guidelines. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection" and "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)

Patients with silicosis are also at risk for nontuberculous mycobacterial infection [125,126]. (See "Overview of nontuberculous mycobacterial infections" and "Treatment of Mycobacterium avium complex pulmonary infection in adults".)

Other conditions — A number of other conditions are associated with chronic silica exposure [137].

●Chronic necrotizing aspergillosis – A few cases of chronic necrotizing pulmonary aspergillosis have been reported in patients with progressive massive fibrosis [138,139]. In these patients, chest computed tomography demonstrated cavitary lung lesions with mycetoma formation. (See "Chronic pulmonary aspergillosis: Epidemiology, clinical manifestations and diagnosis" and "Chronic pulmonary aspergillosis: Treatment".)

●Lung cancer – The International Agency for Research on Cancer (IARC) determined in 1997 that there was sufficient evidence for carcinogenicity of crystalline silica [140]. Since then, additional evidence for a relationship has accumulated [141], although the relationship may not increase linearly to the highest levels of silica exposure [142-146]. Clubbing is uncommon in silicosis, so this physical finding should prompt careful assessment for malignancy.

Early lung cancers may be missed due to a presumption of progressive silicosis or parenchymal changes of silicosis may be confused with malignancy on chest imaging studies, making lung cancer screening interpretation challenging in cases of more advanced silicosis [147]. After careful review of lung cancer guidelines in conjunction with a discussion of risks and benefits, screening for lung cancer in silica-exposed workers should be considered on a case-by-case basis. Histopathologic confirmation should be considered in the context of a lung nodule which is increasing in size, as PET scanning can be positive in both cancer and silicotic nodules. (See 'Clinical manifestations' above.)

●Rheumatic disease – Silicosis is associated with production of autoantibodies, such as antinuclear antibody and rheumatoid factor. In addition, occupational silica exposure is associated with systemic sclerosis [148-150] and rheumatoid arthritis [148,151-154]. Case reports of other autoimmune conditions such as Sjögren's disease, dermatomyositis, Graves disease, autoimmune hemolytic anemia, and pemphigus vulgaris also have been reported in patients with occupational exposure to silica [155-158]. Associations with systemic lupus erythematosus, mixed connective tissue disease, and systemic vasculitis are less well established [5,137,148,159-164]. (See "Risk factors for and possible causes of systemic sclerosis (scleroderma)", section on 'Noninfectious environmental factors'.)

●Chronic kidney disease – Population-based studies have shown a positive relationship between occupational silica exposure and chronic kidney disease (CKD) [143,165,166]. A dose-response trend of increasing CKD risk with increasing duration of silica exposure was observed in one large study and was particularly strong among non-White workers [162]. In contrast, later studies did not find evidence of a dose-response relationship between CKD and duration of silica exposure [167-170].

●Airflow limitation and chronic bronchitis – Silica exposure, even in the absence of findings on conventional chest radiograph, is associated with excessive decline in spirometric performance [80-82]. Cough and sputum production are common among workers with occupational exposure to silicosis. Smoking may potentiate the increased risks of emphysema and chronic bronchitis from silica exposure [171,172].

●Sarcoidosis – Silicosis and sarcoidosis have similar clinical features and, without comprehensive diagnostic evaluation and exposure history, may be mistaken for one another. The similarities are complicated by epidemiologic studies assessing possible occupational and environmental exposure associations with sarcoidosis have suggested a link to RCS [173,174].

PREVENTION — Silicosis is a preventable disease. As a consequence of better industrial hygiene practices, silicosis afflicts far fewer people in the United States than in the past [17]. The 2017 Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for respirable silica is a time weighted average of 50 microg/m³ over an eight hour shift [175-178]. The standard also includes other requirements for exposure assessment, methods for controlling exposure, respiratory protection, medical surveillance, hazard communication, and record-keeping. A number of studies suggested that the previous PEL of 100 microg/m³ was not protective of workers with exposure over an entire working lifetime [24,76,179,180]. Unfortunately, noncompliance with even the current PEL levels appears common [181].

NIOSH also recommends use of half-face particulate respirators with N95 or better filters for airborne exposures to silica at concentrations of 50 microg/m³ or less [182]. Above this concentration of crystalline silica, powered respirators are recommended [176].

Although primary prevention through exposure control is the critical component of silicosis prevention, health monitoring of workers with exposure to respirable crystalline quartz using chest radiographs and spirometry may assist in the early identification of people developing disease from their exposures. Efforts at secondary prevention only work if there are effective interventions resulting in reductions of quartz exposure for affected workers and others comparably exposed. Many industrialized countries mandate health surveillance for workers at risk of developing silicosis [183]. A number of NIOSH publications are available addressing such issues as awareness of silica as a workplace hazard, environmental controls, personal protection, and medical monitoring [184-186].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pneumoconiosis".)

SUMMARY AND RECOMMENDATIONS

●The crystalline forms of silica (eg, quartz, cristobalite, and tridymite) are associated with a spectrum of pulmonary diseases known collectively as silicosis. Workers in a broad range of industries (eg, sandblasting, mining, masonry, foundry work, glass and ceramic manufacturing) are exposed to respirable silica (silicon dioxide) (table 1). (See 'Forms of silica and mechanism of toxicity' above and 'Silica in the work environment' above.)

●Three patterns of silicosis have been described.

•Acute silicosis, also known as acute silicoproteinosis, develops after exposure to high concentrations of respirable crystalline silica and results in symptoms within a few weeks to a few years after the initial exposure. Symptoms include cough, weight loss, fatigue, and sometimes pleuritic pain. It is associated with a bilateral alveolar filling pattern, similar to that of pulmonary alveolar proteinosis. (See 'Acute silicosis' above and 'Imaging' above.)

•Chronic silicosis (includes simple silicosis and progressive massive fibrosis) has multiple, upper lung zone nodules that are rounded and less than 10 mm in diameter. It typically appears 10 to 30 years after exposure. Progressive massive fibrosis refers to coalescence of the nodules of chronic silicosis in association with hilar lymphadenopathy and calcification. Presentations vary from asymptomatic radiographic findings to progressive respiratory insufficiency. (See 'Chronic silicosis' above.)

•Accelerated silicosis develops within 10 years of the initial exposure and is associated with high level exposure. The radiographic pattern overlaps with acute and chronic simple silicosis although the development of radiographic abnormalities is more rapid. Patients with accelerated silicosis are at greater risk for progressive massive fibrosis. (See 'Accelerated silicosis' above.)

●The diagnosis of acute silicosis is based upon the history of an acute, high dose silica exposure, imaging findings of diffuse nodular and patchy consolidative opacities, a bronchoalveolar lavage (BAL) effluent that is milky and lipoproteinaceous, and exclusion of other potential explanations (infection, pulmonary edema, alveolar hemorrhage, eosinophilic pneumonia, primary pulmonary alveolar proteinosis). (See 'Diagnosis' above.)

●The diagnosis of chronic silicosis is based on the combination of a history of sufficient respirable silica exposure to cause the clinical findings, a compatible chest radiograph, and the absence of an alternative explanation. Lung biopsy is reserved for situations in which a confident clinical diagnosis cannot be made (eg, insufficient occupational exposure history, imaging suggestive of malignancy or infection). (See 'Diagnosis' above.)

●For all forms of silicosis, further exposure to silica should be avoided or minimized, if complete avoidance isn’t possible. No specific therapy has been established for any form of silicosis. Symptomatic therapy includes smoking cessation (if needed), treatment of airflow limitation with bronchodilators, vaccination against influenza and pneumococcus, and use of supplemental oxygen (if indicated) to prevent complications of chronic hypoxemia. (See 'Treatment' above.)

●Patients with advanced silicosis and no contraindications may be candidates for lung transplantation. (See 'Lung transplantation' above.)

●Conditions associated with silicosis include mycobacterial and fungal infection, airflow obstruction, chronic bronchitis, autoimmune diseases, chronic kidney disease, and lung malignancy. (See 'Other conditions' above.)

●As there is no proven therapy for silicosis, efforts should be directed towards prevention through a comprehensive lung health protection program focused on exposure avoidance and use of personal protective equipment. (See 'Prevention' above.)