Are the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and the undifferentiated connective tissue disease (UCTD) related to each other? A case-control study of environmental exposures. Scanzi F1, Andreoli L1, Martinelli M1, Taraborelli M1, Cavazzana I1, Carabellese N1, Ottaviani R1, Allegri F1, Franceschini F1, Agmon-Levin N2, Shoenfeld Y2,3, Tincani A4. Author information 1Department of Clinical and Experimental Sciences, University of Brescia, Rheumatology and Clinical Immunology, A.O. Spedali Civili, Piazzale Spedali Civili,1, 25123, Brescia, Italy. 2Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. 4Department of Clinical and Experimental Sciences, University of Brescia, Rheumatology and Clinical Immunology, A.O. Spedali Civili, Piazzale Spedali Civili,1, 25123, Brescia, Italy. firstname.lastname@example.org. Abstract The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an entity that includes different autoimmune conditions observed after exposure to an adjuvant. Patients with undifferentiated connective tissue disease (UCTD) present many signs and symptoms of ASIA, alluding to the idea that an exposure to adjuvants can be a trigger also for UCTD. The aim of this case-control study was to investigate exposure to adjuvants prior to disease onset in patients affected by UCTD. Ninety-two UCTD patients and 92 age- and sex-matched controls with no malignancy, chronic infections, autoimmune disease nor family history of autoimmune diseases were investigated for exposure to adjuvants. An ad hoc-created questionnaire exploring the exposure to vaccinations, foreign materials and environmental and occupational exposures was administered to both cases and controls. Autoantibodies were also analyzed (anti-nuclear, anti-extractable nuclear antigens, anti-double-stranded DNA, anti-cardiolipin, anti-β2 glycoprotein I). UCTD patients displayed a greater exposure to HBV (p = 0.018) and tetanus toxoid (p < 0.001) vaccinations, metal implants (p < 0.001), cigarette smoking (p = 0.006) and pollution due to metallurgic factories and foundries (p = 0.048) as compared to controls. UCTD patients exposed to major ASIA triggers (vaccinations, silicone implants) (n = 49) presented more frequently with chronic fatigue (p < 0.001), general weakness (p = 0.011), irritable bowel syndrome (p = 0.033) and a family history for autoimmunity (p = 0.018) in comparison to non-exposed UCTDs. ASIA and UCTD can be considered as related entities in the "mosaic of autoimmunity": the genetic predisposition and the environmental exposure to adjuvants elicit a common clinical phenotype characterized by signs and symptoms of systemic autoimmunity.