AAV Cases Near Quarries Support Silica as Environmental Trigger, Study Says

The likelihood of developing ANCA-associated vasculitis rises significantly among people living near quarries that extract quartz with silica, a data analysis from France reported. 

Its findings also support silica exposure as a specific environmental risk factor for this disease. 

The analysis, “Prevalence of antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis and spatial association with quarries in a French Northeast region,” was published in the journal Arthritis & Rheumatology. 

The causes of ANCA-associated vasculitis (AAV), a group of autoimmune diseases characterized by blood vessel inflammation, are largely unknown. 

Studies suggest both genetic and environmental factors play a role in triggering the immune system to mistakenly attack white blood cells called neutrophils, and damage blood vessels. Disease symptoms vary, depending on the sites of vascular damage. 

Exposure to silica — most commonly found in nature as quartz — has been shown to contribute to AAV’s development, and that of several autoimmune diseases, including lupus, rheumatoid arthritis, and systemic sclerosis. 

Quarries, a place where rocks, sand, and minerals are extracted, are sources of silica exposure. No study to date, however, has shown a geographical association between quarries and AAV. 

Alsace is a small region in eastern France, bordering Germany and Switzerland. Due to the proximity of the Vosges mountain range on the west, the density of quarries in Alsace is high compared with other regions in France.

Investigators with the Hôpitaux Universitaires de Strasbourg, the region’s capital city, examined the prevalence of AAV subtypes in Alsace and their association by proximity to local quarries for the 2016 calendar year.

A total of 185 AAV cases were identified from hospital records, immunology laboratories, and the National Health Insurance System. Most of the patients were male (57%), ranging in age from 12 to 91, with a median disease duration of five years.

Of these people, 120 were diagnosed with granulomatosis with polyangiitis (GPA), 35 had microscopic polyangiitis (MPA), and 30 with renal limited vasculitis (RLV). 

Evidence of blood vessel inflammation or granuloma — small lumps of immune cells — was observed in 139 patients (75%). Antibodies that target proteinase 3 (PR3) within neutrophils were found in 57% of patients, while the remaining tested positive for antibodies against myeloperoxidase (MPO).

Analysis revealed that the 2016 estimated prevalence of AAV in Alsace was 101.5 cases per million inhabitants. For GPA, the prevalence was 65.5 cases per million inhabitants, 19.1 for MPA, and 16.8 for RLV. 

“Notably, the prevalence of GPA in our study was almost three times higher than that of Seine-Saint-Denis [a northeastern suburb of Paris], while the prevalence of MPA was comparable,” the team wrote. In contrast, “the prevalence of GPA and MPA in Alsace are quite close to those found in other European countries over the last 20 years.”

The prevalence of those with anti-PR3 antibodies was 56.9 cases per million inhabitants, and 38.1 for anti-MPO antibodies.

Quarry density was calculated by the number of quarries divided by the surface area of Alsace. Six people who did not reside in Alsace at the time of diagnosis were excluded from this analysis. 

Overall, the risk of AAV was 2.5 times higher in communities that contained quarries than in those that did not. For GPA, the risk was 3.2 times higher, and for RLV, 3.1 times higher. No reported increase in risk was seen for MPA. 

A significant spatial association was seen between GPA cases and quarries, using a separate spatial statistical model. But no such association existed between GPA cases and randomly distributed points, suggesting “the significant spatial association between GPA and quarries was not random,” the researchers wrote. 

While close to statistical significance, there was no association between MPA or RLV and mineral extraction sites, or with AAV as a whole. The investigators pointed out that “the study may have been underpowered to demonstrate such an association, due to the limited number of cases for those two diseases.”

An almost threefold higher risk of anti-PR3, and a 2.3 increased risk for anti-MPO, was found in communities with quarries compared with those without them, and significant association found between the presence of quarries and anti-PR3 and anti-MPO antibodies. 

These results “further support the role of silica exposure in AAV, regardless of clinical subgroups such as GPA, MPA or RLV,” the researchers wrote. 

“The present study reveals a higher prevalence of GPA in an eastern French region with a high density of quarries,” the team concluded. “It demonstrates a geospatial association between AAV and quarries and supports the role for a specific environmental factor.”

Further work into “the duration and intensity of exposure to inhaled particles, including crystalline silica, and AAV development” is needed, the researchers added.