The cause of sarcoidosis: the Centurial enigma solved.

I am an experienced pathologist (4 decades), and I can now confidently perceive the cause of sarcoidosis. I can see clearly now because of 2 things: (1) modern evidence indicating a genetic-based immune dysregulation as an essential predisposing causal cofactor and (2) a century of accumulated pathology observations relevant to the point. The first factor helps explain numerous environmental, clinical, and research uncertainties, contradictions, and puzzles. The second factor, not readily available to clinicians, allows me to perceive the answer. The argument: (1) although most pathologists are vague in their conception of a "granuloma," the discerning pathologist realizes that a "true," well-formed epithelioid granuloma has only a very limited number of possible causes; (2) these causes do not include autoimmune diseases nor "self-perpetuating" granulomas to a "cleared" infectious agent; (3) the only feasible 2 causes are an infection or a reaction to a foreign particulate; (4) the only possible infections are ones where the infectious agent can be seen under the microscope; (5) experienced infectious disease pathologists do not see a microorganism (after a century of looking); (6) foreign particulates are therefore the cause (the only feasible cause remaining). This is not a new speculation; what I contribute that is new are pathology perceptions that confirm it beyond speculation. The reason the particles are not seen microscopically is that they are nanoparticles (less than a micrometer in largest dimension); larger particles are cleared from the lung efficiently by mucociliary transport. Direct evidence for this nanoparticulate theory is abundant. A recent case I studied has some compelling details. The nanoparticle theory should be accepted and acted upon, guiding further research, and there are risk-free measures that probably could benefit patients now.