Physicians are often puzzled by patients who suffer from a complex array of signs and symptoms that cannot easily be categorized into a single defined autoimmune or autoinflammatory disease. Such enigmatic conditions, although common in clinical practice, are rarely reported in the medical literature because they are so diverse and often present with nonspecific and vague findings. Not surprisingly, their pathogenesis remains a mystery. Moreover, possible therapies for these patients are difficult–if not impossible–to evaluate because most clinical trials are designed to follow patients with well-defined diseases and involve validated outcomes that often include specific markers.
As an example of such a complicated and perplexing situation, consider the following recently published case.1 The report described a 56-year-old woman diagnosed with chronic fatigue, fibromyalgia, weakness, headaches, difficulties concentrating, short-term memory impairment, and evidence of a demyelinating illness. Laboratory testing indicated the presence of high levels of antiadrenal, antistriated muscle, and antismooth muscle antibodies; increased rheumatoid factor titers; and elevated immunoglobin (Ig) G, IgM, and IgA immune complexes. The patient’s illness had begun 13 years earlier following the second dose of hepatitis B vaccine and was aggravated by the third vaccination. In addition, several years before vaccination, the patient had undergone uneventful silicone breast implantation. However, during the time between her second and third vaccination, she suffered a breast injury accompanied by evidence of local inflammation. Four years afterwards, she underwent removal of her breast implants. On histological examination, leaking of silicone and extensive calcification in both breasts was observed. In addition to removal of the implants, the patient was treated with intravenous IgG, and her condition gradually improved.
This illustrative case is notable for several clues that suggest a possible role of exposure to the hepatitis B vaccine and silicone leak that, together, produced an augmented adjuvant effect and led to the patient’s condition. In recent years, a large body of evidence has accumulated on the basis for vague conditions such as chronic fatigue and sick building syndromes. Subsequently, other poorly defined (and sometimes controversial) conditions—for example, siliconosis (relating to manifestations occurring following exposure to silicone) and postvaccination phenomena such as Gulf War syndrome (GWS) and the macrophagic myofasciitis syndromes (MMF)—have been suggested to have a common pathogenesis.2-5
Because these enigmatic diseases can display similarities in the presenting complex of signs and symptoms, a shared etiological common denominator is possible. In addition, accumulating data regarding immune adjuvant activity stimulated by various substances (e.g., infectious agents, silicone, aluminum salts) have been associated with the pathogenesis of each of these conditions. Thus, their comparable clinical presentation and plausible common mechanisms have led to the convergence of these conditions under a common syndrome called autoimmune (autoinflammatory) syndrome induced by adjuvants (ASIA).6
Autoimmunity Induced by Adjuvant
The worldwide prevalence of autoimmune and autoinflammatory diseases is determined by the interplay of genetic and environmental factors.7 The latter factors include infections, toxins, drugs, and others agents that can be linked by the occurrence of immune-mediated diseases as well as the nature of the clinical manifestations and their severity.8,9 The mechanisms by which these environmental factors trigger autoimmunity are diverse but, as a group, they may incorporate an adjuvant effect. An adjuvant is a substance that enhances the activation of the immune system, both the innate and the adoptive ones.10-12