Silicosis: what is it, symptoms, causes, treatment, prognosis

What is silicosis?

SilicosisIs a professional lung diseasecaused by inhalation of crystalline silica dust. It is characterized by inflammation and scarring in the form of nodular lesions in the upper lobes of the lungs. Lung silicosis is a type of pneumoconiosis. The disease (especially acute form) is characterized by shortness of breath, cough, fever and cyanosis (bluish skin). It is often mistaken for pulmonary edema (fluid in the lungs), pneumonia or pulmonary tuberculosis.

In 2013, at least 43,000 people died of silicosis worldwide, up from 50,000 in 1990.

Signs and symptoms

Because chronic silicosis develops slowly, signs and symptoms may not appear until years after the illness. Signs and symptoms include:

• dyspnea (shortness of breath), worse with exertion;
• cough, often persistent, sometimes violent;
• fatigue;
• tachypnea (rapid breathing), which is often difficult;
• loss of appetite and weight loss;
• chest pain;
• heat;
• gradual darkening of the skin;
• gradual, dark, shallow cracks in the nails eventually lead to tears as the protein fibers inside the nail bed break down.

In advanced cases, the following also occurs:

• cyanosis, pallor of the upper body (blue skin);
• cor pulmonale (right ventricular heart disease);
• respiratory failure.

Causes and risk factors

In nature, there are two forms of silicon dioxide: amorphous and crystalline. The crystalline form of silica is a rich natural mineral commonly found in substances such as sandstone, quartz and granite. Although inhalation of the amorphous form does not appear to cause clinically significant complications, inhalation of the crystalline compound can lead to lung disease.

Since silica is deposited in the airways, contact with the alveolar and endobronchial surfaces generates reactive oxygen species. Smaller particles, through phagocytosis, enter macrophages, which generate additional free radicals. Oxidative damage by activated macrophages and silica particles results in the release of inflammatory cytokines, increased cell signaling and apoptosis parenchymal cells and macrophages. Infiltration of fibroblasts occurs in the form of nodes as the disease progresses.

Many occupations can put workers at risk of exposure to silica dust in a wide variety of industries. High-risk occupations include road repair, concrete production, coal mining, brickworking, and rock excavation. Workers involved in stone cutting, oil extraction, metalworking, sandblasting, etc. are also at risk.

Epidemiology

More than two million workers are exposed to some form of inhaled silica on a regular basis, according to the Occupational Safety and Health Administration. Increased awareness and safety measures in the workplace have led to a significant decrease in the incidence of this disease over the past several decades; however, precautions remain imperfect and new cases of silicosis continue to arise.

Pathophysiology

Inhalation of crystalline silicon dioxide causes the formation of mineral deposits at the level of the terminal bronchioles and alveoli. The presence of foreign material leads to the activation of alveolar macrophages, and also has a direct toxic effect on the surrounding lung parenchyma. Cell damage results in the release of inflammatory cytokines (such as IL-1 and TNF-alpha), the formation of free radicals, and an increase in cellular signaling pathways. Various cytokines cause the development of fibrosis. The role of tissue mast cells has also been reported. There is also evidence that silica interferes with the ability of macrophages to inhibit the growth of mycobacteria, and this effect explains the general silicosis / tuberculosis association. In the acute form of silicosis, there is a direct toxic effect on type 2 alveolar cells, as well as on macrophages. The role of immunological factors in pulmonary silicosis has long been postulated but not proven.

Histopathology

Nodular silicosis is characterized by the presence of silicotic nodules. In general, silicite nodules are solid, discrete, rounded formations containing varying amounts of black pigment. Nodules typically occur around the respiratory bronchioles and small pulmonary arteries, as well as in the subpleural and paraseptal areas. The progressive expansion causes obliteration of the small airways and pulmonary vessels. The latter are characterized by concentrically arranged bundles of hyalinized collagen surrounded by varying numbers of dust-filled histiocytes. In the early nodules, fibroblasts and histiocytes with acellular collagen plates are secreted. Small polarizable, doubly refracting, round or oval particles are often found within the nodules. Their presence helps to confirm the diagnosis, but in some cases they may be absent and they are not specific for silicosis. A granulomatous reaction can be observed in the capsule of silicotic nodules. Its presence increases the likelihood of coexistence of mycobacterial infection. Central necrosis is uncommon. The surrounding lung may be unremarkable, although dust spots and pigmented macrophages are usually seen around the small airways. Occasionally, a non-specific type of interstitial fibrosis has been reported in patients with chronic silicosis.

In acute silicosis, microscopic findings mimic pulmonary alveolar proteinosis. In contrast to normal alveolar proteinosis, interstitial inflammation and fibrosis or irregular hyaline scars are also commonly seen, as well as varying amounts of pigment. The silicosis nodules are poorly formed or in most cases absent.

Microscopic examination can be helpful in detecting some complications, including progressive massive fibrosis or tuberculosis, and non-tuberculous infections. Progressive massive fibrosis is characterized by the presence of nodular fibrosis larger than 1 cm. Usually there is a large amorphous mass of fibrous tissue, which consists of conglomerated nodules that cause obliteration and contracture of the lung parenchyma. this lesion also occurs in other pneumoconiosis, including asbestosis, pneumoconiosis of miners or mixed dust fibrosis. When faced with a granulomatous infection with necrosis, tuberculosis and non-tuberculous mycobacteriosis can be suspected.

Diagnostics

There are three key elements in the diagnosis of lung silicosis. First, the patient's history must reveal exposure to sufficient silica dust to cause this disease. Second, imaging of the chest (usually a chest X-ray), which shows signs consistent with silicosis. Third, there are no underlying diseases that are more likely to cause abnormalities. The physical examination is usually unremarkable unless there is a complex medical condition. Also, the results of the examination are non-specific for silicosis. Pulmonary function tests can reveal airflow restriction, restrictive defects, decreased diffusion capacity, mixed defects or may be normal (especially without complications). In most cases, silicosis does not require a tissue biopsy for diagnosis, but in some cases it may be necessary primarily to rule out other conditions.

In uncomplicated silicosis, a chest x-ray will confirm the presence of small (<10 mm) nodules in the lungs, especially in the upper regions of the lungs. The lesion and abundance of the lung zone increases as the disease progresses. In advanced cases of silicosis, large opacities (> 1 cm) result from the confluence of small opacities, especially in the upper areas of the lungs. When the lung tissue is drawn in, compensatory emphysema occurs. Enlargement of the hilum is common in chronic and accelerated silicosis. In about 5-10% of cases, the nodules calcify in the periphery, causing what is called eggshell calcification. This finding is not pathognomonic (diagnostic) for silicosis. In some cases, pulmonary nodules may also become calcified.

Computed tomography (CT) scans can also provide detailed analysis of the lungs and detect cavitation due to concomitant mycobacterial infection.

Classification

The classification of silicosis is based on the severity of the disease (including radiographs), the onset and rate of progression. These include:

- Chronic simple silicosis.

Usually results from prolonged exposure (10 years or more) to relatively low concentrations of silica dust and usually appears 10-30 years after the first exposure. This is the most common type of silicosis. Patients with this type of disease, especially at an early stage, may not have overt signs or symptoms of the disease, but abnormalities can be detected with X-rays. Chronic cough and exertional shortness of breath are common. Radiographically, in chronic simple silicosis, an abundance of small (<10 mm in diameter) opacities is revealed, usually of a rounded shape and prevailing in the upper zones of the lungs.

- Accelerated silicosis.

Silicosis, which develops 5–10 years after the first exposure to higher concentrations of silica dust. Symptoms and radiographic findings are similar to chronic simple silicosis, but occur earlier and tend to progress more rapidly. Patients with accelerated silicosis are at greater risk of developing complicated disease, including progressive massive fibrosis (PMF).

- Complicated silicosis.

Silicosis can be "complicated" by the development of severe scars (progressive massive fibrosis, also known as conglomerate silicosis), when small nodules gradually merge, reaching a size of 1 cm or more. PMF is associated with more severe symptoms and respiratory distress than the simple type of disorder. Silicosis can also be complicated by other lung diseases such as tuberculosis, non-tuberculous mycobacterial infection and fungal infection, some autoimmune diseases, and lung cancer. Complicated silicosis is more common with accelerated silicosis than chronic silicosis.

- Acute silicosis.

Silicosis that develops from several weeks to 5 years after exposure to high concentrations of respirable silica dust. It is also known as silicoproteinosis. Symptoms of acute silicosis include more rapid onset of severe disabling shortness of breath, cough, weakness, and weight loss, often resulting in death. X-rays usually reveal diffuse alveolar filling with air bronchograms, described as a sign Ground glass, and pneumonia-like, pulmonary edema, alveolar hemorrhage, and alveolar cell carcinoma lungs.

Treatment

There are no specific therapeutic modalities. The primary treatment is to remove the source of exposure and relieve symptoms and prevent further progression of the disease.

Forecast

Previous studies of silicosis have shown that prognosis depends on various factors, including age at diagnosis, history smoking, clinical progression of the disease, genetic polymorphisms, concomitant diseases and conglomerate-nodular diseases on radiography. Genetic polymorphisms of tumor necrosis factor (TNF) -α2 and rs2076304 in the desmoplakin gene have also been associated with an increased risk of death.

Patients who have been heavily exposed to silica for a relatively short period of time can develop accelerated silicosis. This phenomenon is usually associated with a history of exposure of 5 to 15 years, usually 10 years or less. Disease development can continue despite the cessation of silica exposure. Also autoimmune diseases associated with accelerated silicosis.

Patients with chronic silicosis may be asymptomatic even though they may be exposed to silica dust for decades. However, some of these patients may develop progressive massive fibrosis (PMF). Retraction of the PMF can cause emphysematous changes in the basilar regions of the lungs. These patients are prone to developing hypoxic respiratory failure, mycobacterial infections, and pneumothorax. The cause of death is invariably respiratory failure.

Complications

—​ Koch's wand(Mycobacterium tuberculosis)and mycobacterial infections not associated with tuberculosis.

In patients with silicosis, the risk of mycobacterial infections increases by 8-20 times. Dysregulation of cell death pathways can lead to the fact that macrophages exposed to dioxide silicon, will have increased expression of tumor necrosis factor alpha (TNFα), interleukin (IL) -1b and expression caspase-9. Once infected with mycobacteria, these macrophages promote necrosis rather than apoptosis, which leads to the release of viable mycobacteria from necrotic cells and the progression of a latent disease into an active one.

— Autoimmune disease.

Epidemiological data support an increased risk between occupational exposure to crystalline silica dust and the development of autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis and rheumatoid arthritis (RA). The prevalence of SLE among men with high levels of silica exposure is 10 times higher than in the general population. Rheumatoid arthritis (RA) is more common in men with silicosis than in the general population, most likely due to the effects of silica on the immune system. Kaplan's syndrome (silicoarthritis, rheumatoid pneumoconiosis), originally described in coal workers, is characterized by pulmonary nodules with cavitation in silica workers with seropositive RA. It is believed that the presence of elevated levels of autoantibodies, immune complexes and hypergammaglobulinemia in workers exposed to silica may lead to this predisposition. Silica dust causes exposed macrophages to secrete antigenic polysaccharides that activate the reticuloendothelial system. Autoimmune diseases can accompany accelerated silicosis. Therefore, it is important to screen patients as treatment and prognosis may change.

— Chronic obstructive pulmonary disease (COPD).

Previous research has shown that exposure to silica dust can lead to the development of chronic bronchitis, emphysema of the lungs and / or minor respiratory illness even without evidence of radiologically confirmed silicosis. Suggested mechanisms include the following:

• Silica particles trigger the release of neurotransmitters that increase the production of oxidants, cytokines, chemokines and elastase, leading to airway inflammation and emphysema.
• Silica particles cause damage to epithelial cells, which facilitates its penetration through the walls of the small airways, leading to localized fibrosis.

- Cancer.

Controversy over the carcinogenicity of silica arises from the different research methods available, as well as the potential for bias. due to factors affecting the situation, such as smoking cigarettes, as well as exposure to chemicals such as radon, arsenic or polycyclic aromatic hydrocarbons. According to the American College of Occupational and Environmental Medicine, risk lung cancer in patients with silicosis, it is generally greatest in smokers with silicosis, but the risk of cancer in nonsmokers, exposed to silica, silicosis-free is less obvious due to the incomparable results available research. Silica has been classified as a Group 1 human carcinogen since 1997 by the International Agency for Research on Cancer.

- Pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis can occur after exposure to high silica levels. Microscopic examination of bronchoalveolar lavage revealed positive Schiff staining with periodic acid, histologically known as silicoproteinosis.

— Chronic kidney disease (CKD).

Kidney disease, such as nephrotic syndrome, glomerular nephritis and terminal stage renal failure (ESRD) can occur in individuals exposed to silica in the absence of overt pulmonary disease. There is an increased incidence of WBC among workers employed in the production of industrial sand, granite and ceramics.