Bilateral nodular opacities and hilar node enlargement in a 73-year-old man with cough

Discussion

Silicosis is a fibronodular lung disease caused by the inhalation of crystalline silicon dioxide [1]. Despite the established preventive measures, silicosis remains one of the most frequent occupational diseases worldwide [2]. Especially in developing countries, where industrial hygiene measures have not yet achieved the desired safe levels of mineral dust in the workplace, silicosis constitutes a major public health issue. Conversely, in the developed world, despite a steady decline thanks to the established protective measures (dust control and respirator use), silicosis still constitutes an occupational hazard.

The element silicon is one of the most abundant in nature, comprising ∼25% of the earth’s crust. It occurs in crystalline and amorphous forms [3]. Common types of free crystalline forms include quartz, tridymite and cristobilite, while less commonly encountered forms are keatite, coesite and stishovite. Rocks, such as sandstone and granite, are formed by quartz in varying concentrations. Occupational exposure to respirable particles of silica (0.2–10 μm aerodynamic diameter) occurs in diverse occupations and industries, including those where rocks and stones are drilled (mining, quarries) or broken down to dust (sculpting, rock cutting) [1].

The diagnosis of silicosis requires three criteria: 1) history of exposure to silica, 2) compatible radiological features and 3) exclusion of other diseases with a similar presentation [1]. Symptoms are not specific and resemble those of other chronic respiratory diseases, they include cough and progressive shortness of breath on exertion [1]. Thus, occupational history with exposure is the key factor for clinicians to suspect the disease.

Four clinical patterns have been described in the context of silicosis. Chronic simple silicosis represents the most common form, presenting after prolonged exposure to respirable crystalline free silica, usually after 10 years or more [1, 3]. Patients often present with an incidentally found abnormal radiograph with prominent hilar lymph nodes and calcification or nodules of <1 cm in diameter [1]. In 5% of cases, a distinctive peripheral calcification of the hilar lymph nodes, known as eggshell calcification may be seen [1]. Another pattern is that of PMF, in which nodules are >1 cm in diameter and over time progressively increase in size. As these large fibrotic masses contract, associated emphysema develops in the surrounding tissues, while the destruction of the pulmonary capillary network produces increased pulmonary vascular resistance and eventually pulmonary hypertension and cor pulmonale. Accelerated silicosis shares the same features as the classic chronic silicosis form except that the time from initial exposure to silica to presentation of radiographic lesions is much shorter, usually within a 2–5-year period following intense exposure [1]. Finally, acute silicosis presenting as silicoproteinosis is a rare consequence of exposure to high concentrations of silica. Acute silicosis presents with rapidly progressive dyspnoea, respiratory insufficiency and constitutional symptoms, such as fever, fatigue and weight loss [1, 4]. The differential diagnosis includes various diseases that may present with similar features to silicosis, examples include: sarcoidosis, histoplasmosis, chronic fungal infections, tuberculosis, pneumoconiosis, malignancy and idiopathic pulmonary fibrosis [1]. Imaging (mainly chest radiography) constitutes the principal tool of diagnosis. There is limited data concerning the role of ¹⁸F-FDG PET scans in the differentiation of potential PMF lesions or PMF-associated lung cancer. Despite its well-known usefulness in monitoring pulmonary nodules, the ¹⁸F-FDG PET scan seems to be of limited utility in the evaluation of malignancy in the context of PMF due to its high false-positive rate [5, 6]. Spirometry may be normal, although both obstructive and restrictive patterns are reported in silicosis. However, diffusing capacity of the lung for carbon monoxide seems to be the most sensitive marker in the early stages of the disease [7].

Furthermore, exposure to silica has been associated with a variety of diseases. It is well known that the risk of tuberculosis is increased with the severity of silicosis [8]. Moreover, a number of studies have demonstrated an associated risk for developing COPD, lung cancer and autoimmune diseases, including scleroderma and rheumatoid arthritis, with silica exposure [9–11].

With regards to the pathophysiology of the disease, inhalation of crystalline silica dust leads to deposits in the distal airways. There, silica particles interact with the alveolar macrophages [12]. Various in vitro and animal model experiments have demonstrated the activation of the nucleotide-binding domain, leucine-rich repeat protein NALP3, which combines with the intracellular adapter protein ASC activating pro-caspase 1. The result of this signalling pathway is the production of proinflammatory interleukin-1β, which plays a critical role in subsequent inflammation and fibrosis [13, 14].

Currently there is no proven effective therapy for silicosis [1]. Whole lung lavage and corticosteroids have been tried in order to slow disease progression; however, there is no evidence of any long-term benefit with their use [15]. General supportive care is the best that can be offered to these patients (smoking cessation, influenza and pneumococcal vaccination, bronchodilator medication and a high level of vigilance for tuberculosis and for malignancy). Regarding prevention: air quality monitoring, enforced use of protective measures (respirators and clothing) and workplace safety with austere exposure control based on national regulatory strategies represent the most important preventative approaches to reduce the risk of exposure and incidence of silicosis [16].