Figure 4.

Potential initiators of immune-mediated inflammatory conditions at distant sites. A briefly description of the extra-articular potential initiators that might account for the pathogenesis of rheumatic diseases. Patients at high risk to develop autoimmune arthritis are more prone to infections due to endogenous (dysfunctional immune system) and external factors, i.e., periodontal disease and the presence of P. gingivalis and A. actinomycetemcomitans that trigger citrullinated peptides; exposure to risk factors such as smoke and pollutants might lead to the production of neutrophils extracellular traps (NEToses) and anti-citrullinated proteins antibodies (ACPA) in the lung; and the gut dysbiosis that also lead to the ACPA production. For patients at high risk to develop rheumatoid arthritis (RA), meticulous examining for infectious foci, particularly in the intestine and mouth, should be advocated in order to allow their early recognition and eradication.