Nonoccupational Industrial Silica Exposure as a Likely Cause of Fibrosing Childhood Interstitial Lung Disease: A Case Report

İngilizce (OpenAlex)

An 8-year-old girl was referred to our tertiary center after 2 days of chest pain and an external diagnosis of pneumonia. She exhibited no fever, cough, dyspnea, or weight loss. Birth and past medical histories were unremarkable. The family lived in Hisarardı village (Yatağan, Muğla); her father, a quartz-factory worker for 6 years, had been diagnosed with silicosis 1 year earlier. On admission, her vital signs were normal. Physical examination revealed finger clubbing but was otherwise unremarkable. Respiratory system examination and laboratory findings, including C-reactive protein, complete blood count, and chemistry panel, were normal. Chest X-ray showed bilateral reticular opacities and lobar consolidation. She was initiated on sulbactam-ampicillin. Finger clubbing prompted further evaluation. High-resolution computed tomography (HRCT) on day 14 demonstrated diffuse paraseptal emphysema, peribronchial thickening, and patchy ground-glass opacities with upper-lobe predominance (Figure 1a). Pulmonary function tests indicated mild restriction (FEV1/FVC: 113%, ppFVC: 80%, ppFEV1: 90%) and a mildly reduced diffusion rate (DLCOadj: 67%). Six-minute walking test showed normal oxygen saturation with no exercise limitation. Transthoracic echocardiography was normal. Flexible bronchoscopy revealed mucopurulent secretions and hyperemic mucosa. Bronchoalveolar lavage (BAL) cytology was unremarkable; no iron-laden macrophages were identified, and bacterial, mycobacterial, and fungal cultures were negative. Comprehensive evaluations ruled out infectious etiologies (tuberculosis, HIV, viral serologies), autoimmune, and primary immunodeficiency disorders. Subsequently, an open lung biopsy was performed. Histopathological analysis demonstrated subpleural honeycombing, squamous metaplasia, multinucleated cells, cholesterol clefts, and focal lymphoid infiltration, confirming fibrosing childhood interstitial lung disease (chILD) (Figure 1c,d). Whole-exome sequencing found no pathogenic variants in genes associated with monogenic chILD (including surfactant-related genes, TMEM173, COPA, GATA2, and FLNA). We considered initiating systemic corticosteroids and hydroxychloroquine. However, since these agents have uncertain efficacy and require close safety monitoring, and the family—living in a rural village—could not return for close safety monitoring, therapy was deferred. The patient remained clinically stable for 4 years, after which follow-up lapsed for 3 years during the COVID-19 pandemic. At age 15, she re-presented with an 11-month history of exertional dyspnea and a new diagnosis of rheumatoid factor-positive polyarticular juvenile idiopathic arthritis (JIA). She was receiving weekly subcutaneous methotrexate with folic acid and naproxen. Echocardiography showed no pulmonary hypertension. Follow-up HRCT revealed progression of paraseptal emphysema, while spirometry recorded a 10% absolute FVC decline (FEV1/FVC: 116%, ppFVC: 68%, ppFEV1: 79%), indicating progressive pulmonary fibrosis (Figure 1b). A detailed reassessment was conducted. She denied smoking tobacco, e-cigarette, or vaping. A structured screen for hypersensitivity pneumonitis (birds/feather bedding, dampness/mold, and relevant chemicals) was negative. The family, living in a brick house 1.5 km from the quartz mine where the father previously worked, reported recurrent nocturnal silica-dust storms. Given these environmental factors, re-examination of the original lung biopsy identified iron-laden alveolar macrophages and focal iron deposition within pneumocytes (Figure 1e). The overall clinic, radiologic, and pathologic assessment was most consistent with possible nonoccupational industrial silicosis. Because exposure cessation is the key intervention, relocation was advised, but could not be achieved for socioeconomic reasons. Accordingly, although hydroxychloroquine has no established role in silicosis, we initiated off-label hydroxychloroquine as adjunctive therapy for PF. Over a 3-year follow-up, JIA treatment was tapered stepwise and ultimately discontinued. Hydroxychloroquine has been maintained, while nintedanib or pirfenidone could not be initiated because patient's family declined consent. Pulmonary function tests remained similar compared with prior testing (FEV1/FVC: 115%, ppFVC: 72%, ppFEV1: 84% and DLCOadj: 71%) at the last visit. chILD is an umbrella group of diffuse parenchymal lung disorders characterized by persistent respiratory symptoms and/or gas-exchange abnormality with diffuse radiologic involvement, not explained by more common pediatric conditions (e.g., acute infection, asthma/airway malacia, congenital heart disease, aspiration) [1]. Pulmonary fibrosis (PF) in childhood reflects maladaptive repair to lung injury with excessive, disorganized extracellular-matrix deposition and architectural distortion that, if progressive, culminates in respiratory failure and substantial morbidity and mortality. Pathogenesis is likely multifactorial—genetic susceptibility intersecting with environmental and other exposures, epigenetic modulation, and immune dysregulation. Although PF occurs in a subset of chILD, pediatric-specific diagnostic criteria for PF have not been formally established. Current frameworks, therefore, rely on clinical manifestations, HRCT features, and histopathology to classify PF according to underlying disease categories—lung-intrinsic (native diffuse parenchymal) disorders, systemic/autoimmune disease–related, or exposure-related conditions. Silicosis is an irreversible fibrotic lung disease caused by the inhalation of crystalline silica [2]. While it is a well-recognized and preventable occupational respiratory disease worldwide, nonoccupational exposure [environmental (e.g., natural dust and sandstorms in Sahara desert) or industrial] can also lead to silicosis [2, 3]. Industrial nonoccupational silicosis among children and adults results from silica dust exposure in residential areas near mining and grinding factories, which remains under-researched and under-reported [3, 4]. A study from India demonstrated significantly markedly elevated ambient quartz levels near stone-pencil facilities driven by dust-exhausting fans and concluded that entire villages were at risk [3]. Murlidhar described an 11-year-old boy with silico-tuberculosis, living near sandstone mines in India, with maternal occupational exposure [4]. Chronic simple silicosis, the most common occupational form, typically develops after approximately 10 years of low-level silica exposure and is characterized by the presence of silicotic nodules. However, data on nonoccupational silicosis remains limited, primarily based on environmental silica concentration studies [2-4]. Silicosis has no established curative therapy; early recognition and complete cessation of exposure—ideally before the development of fibrosis—are critical [1]. As in fibrosing chILD, there are no randomized controlled trials evaluating hydroxychloroquine, systemic glucocorticoids, or antifibrotic agents (e.g., nintedanib) for silicosis; evidence is limited to small case series [1, 2]. Silica exposure is linked to systemic complications, including autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis), immune-mediated conditions (chronic kidney disease, thyroiditis), and malignancies. Epidemiologic studies indicate an increased risk of rheumatoid arthritis following silica exposure [5, 6]. Despite the absence of silicotic nodules—unlike in occupational silicosis—the combination of strong exposure history, HRCT showing upper-lobe–predominant fibrosis, slow clinical progression, and tissue iron deposition favored a diagnosis of possible nonoccupational industrial silicosis. Previous studies indicate that intrapulmonary iron, together with silica, contributes to disease progression [7]. Moreover, competing etiologies were systematically excluded. Despite the later development of JIA, the earlier onset of fibrosis, along with imaging and histologic features, did not support polyarticular JIA-associated ILD. In conclusion, this is the first reported case of possible nonoccupational industrial silicosis from secondary exposure to quartz mining in Turkey. In the etiologic evaluation of a child with fibrosing ILD, nonoccupational industrial silicosis should be considered, and a detailed assessment of the patient's residential area and surrounding industry should be undertaken. Ece Ocak: writing – original draft, investigation. Pervin Korkmaz: methodology, supervision, formal analysis, writing – review and editing. Recep Savaş: data curation, methodology, writing – review and editing. Göktuğ Aydoğan: formal analysis, writing – review and editing. Zehra Nur Töreyin: writing – review and editing, visualization. Figen Gülen: writing – review and editing, conceptualization. Esen Demir: conceptualization, supervision, writing – review and editing. The authors have nothing to report. The study was approved by the Ege University Faculty of Medicine Ethics Committee (23-4.1T/26). Written informed consent was obtained from the patient and her parents. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no data sets were generated or analyzed during the current study.