The spectrum of ASIA: 'Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants'.

Physicians are often puzzled by enigmatic medical conditions or the abrupt appearance of an immune-mediated disease. Such a story was recently presented to us by a young Sheikh. A Saudi Sheikh, who suffered at the age of 27 from joints pains, rash and serological evidence of antiRo antibodies, was diagnosed with probable systemic lupus erythematosus (SLE) at that time. He was treated with Plaquenil for a year, but as no signs of SLE were apparent, treatment was stopped and he remained disease free for the next 12 years. At the age of 39 years, 2 weeks after immunization with the flu vaccine, his disease reemerged. This time he presented with severe arthritis and pericarditis, which required treatment with high doses of steroids. This patient’s story illustrates the acceleration of an autoimmune or immune-mediated condition following exposure to external stimuli. During the past year a new syndrome was introduced and termed ASIA, ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’. This syndrome assembles a spectrum of immune-mediated diseases triggered by an adjuvant stimulus. The use of medical adjuvants has become common practice and substances such as aluminum adjuvant are added to most human and animal vaccines, while the adjuvant silicone is extensively used for breast implants and cosmetic procedures. Furthermore, ‘hidden adjuvants’ such as infectious material or house molds have also been associated with different immune mediated conditions. The adjuvant effect has been recognized for years, and is broadly utilized to enhance desired antigen-specific immune responses. This effect is accomplished via mechanisms that impinge on both the innate and adaptive immune systems. Formerly, adjuvants were thought to pose little or no independent threat. Alas, studies of animal models and humans demonstrated the ability of some of them to inflict autoimmunity and immune-mediated diseases by themselves. Intriguingly, although exposure is common, adjuvant disease is relatively rare. It has been suggested that for a clinically overt adjuvant disease additional risk factors are required such as genetic susceptibilities or the co-exposure to other environmental factors. This special issue of Lupus is dedicated to ASIA and contains diverse articles from different geographical areas which provide a broad view of the clinical manifestations as well as the mechanisms related to the adjuvant effect. The link between silicone, a synthetic polymer, and immune-mediated diseases has been accepted by the medical community and is one of the cornerstones of ASIA. Nevertheless, the association between ‘siliconosis’ and systemic sclerosis remains controversial and is reviewed herein by Lidar et al. This review describes the mechanisms by which silicones mediate autoimmunity in general as well as the evidence for a casual association between this adjuvant and specific autoimmune diseases, such as systemic sclerosis. Following the same path Kivity et al. present the case of a patient from the Middle East diagnosed with an overlap between morphea and eosinophilic fasciitis in association with breast implants. This siliconerelated skin disease is within the spectrum of systemic sclerosis. From the other side of the globe Jara et al. and Vera-Lastra et al. report a patient with Still’s disease after silicone implantation as well as a cohort of patients with severe local and systemic diseases following the illegal use of oil adjuvants for cosmetic purposes. The latter comprise of 50 patients, of which 41 were injected with mineral oil and 9 with other substances (e.g. iodide gadital, guyacol). Thirty of them presented with non-specific autoimmune disease and 20 Correspondence to: Yehuda Shoenfeld, MD, FRCP, Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. Email: [email protected]