Taking it all together, it seems that enigmatic but nevertheless common and often disabling complaints can coincide in many individuals diagnosed with siliconosis, MMF, GWS, or postvaccination events (see Table 1). Additionally, in up to 35% of these patients, autoimmunity (e.g., autoantibodies) or an overt autoimmune disease may eventually be diagnosed. A noteworthy common denominator is that the exposure to a component that comprises an adjuvant effect can be documented in each of those medical conditions. These phenomena can occur weeks and even or years following exposure to a culprit agent. Moreover, genetic links observed in animal models, and in the human disease MMF, bring about the notion that the adjuvant effect promotes the appearance of an adjuvant disease in subjects who are genetically susceptible or in those who encounter an additional trigger, such as the effect of another deleterious environmental factor (e.g., infectious agent) or co-exposure to more than one adjuvant.

Last but not least, these medical conditions were recently encompassed as ASIA. Looking back at the numerous reports in the last four or even five decades, one might ask if this is actually a new syndrome. Apparently, physicians have observed these phenomena for years, but the lack of definition remained a major obstacle in diagnosing, treating, and conducting basic as well as clinical studies.

Perhaps the most novel aspect of this new syndrome is its spacious view of these comparable diseases as well as improvement of their definition and diagnosis utilizing major and minor criteria (see Table 2). This innovative characterization may provide physicians a better way to understand to the immune consequences of environmental adjuvants and advance the diagnosis of patients suffering from the adjuvant diseases. Moreover, unraveling the adjuvant diseases pathogenesis may facilitate the search for preventive and therapeutic interventions such as immune modulation of the adjuvant pathways (e.g., TLRs , inflammasome, and others).

Dr. Shoenfeld is head of the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (affiliated with Tel-Aviv University), Tel-Hashomer, Israel. Dr. Levine is a senior physician in the Zabludowicz Center.


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