Table 2.

Disease definition, Inclusion and exclusion criteria and clinical and laboratory evaluation.

Disease definition	Foreign body modelling reaction (i.e. Iatrogenic Alogenosis) Diagnosis One of the following •Local manifestations: edema, angioedema, skin induration, plaques, panniculitis, swelling/tender nodules (with or without fistulization or discharge of sterile pus or filler material), non-infectious adverse reactions related to filler injection OR •Systemic reactions: fever, arthralgia, arthritis, myalgia, muscle weakness, chronic fatigue, generalized aches, distant skin lesions, xerophthalmia, xerostomia [7,9].
	Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) Diagnosis All patients underwent a complete evaluation to see if they fulfilled the criteria as by criteria: •Defined by Shoenfeld’s et al [19]
Inclusion criteria	First time consultation patients with clinical manifestations (local or systemic) of foreign body modelling reaction were included. From this group, those with a biopolymer injection in the gluteal region with or without a previous history of surgical removal of the material were chosen.
Exclusion criteria	•Patients with an established diagnosis of autoimmune disease (Systemic Lupus Erythematosus, Rheumatoid Arthritis, Sjogren’s syndrome) according to ACR/EULAR guidelines 2019, 2010, 2016 respectively for each autoimmune disease. •Previous thyroid disease. •Previous neoplastic disease before the exposure to allogenic substances or at the moment of the medical consultation (If it was not possible to establish the temporal relationship between the application of the allogenic substance and the disease).
Clinical Evaluation (At baseline and every three months)	•Detailed clinical record of demographic data, present or previous comorbidities and familial background (including familial autoimmunity [28] toxic exposure, obstetric outcomes, and other comorbidities. •Complete rheumatological examination searching for autoimmune diseases (by a rheumatologist) based on fulfilled standard validated criteria (baseline for exclusion criteria and follow up). •Muscular strength evaluation (MRC) [29] •Unstimulated Whole Salivary Flow [30] •Fatigue based on the Functional Assessment of Chronic Illness Therapy (FACIT) [31] (those positive were evaluated using the Spanish version of the Fatigue Severity Scale) [33].
Biopolymer injection characteristics	•Date of polymer infiltration. •Type and volume of the injected substance. •Area of infiltration. •Latency time with Foreign body modelling reaction were reported.
Laboratory and Imaging examination	Standard blood samples were collected for the following measurements (All of these tests were repeated every year during follow-up): •Acute-phase reactants: C-Reactive Protein (CRP), and erythrocyte sedimentation rate (ESR) •Liver function (Glutamic Oxaloacetic Transaminase (GOT)), and Glutamic Pyruvic Transaminase (GPT) •Immunological profile: immunoglobulin levels (IgG-IgM)), Antinuclear Antibodies (ANAs), Antineutrophil Cytoplasmic Antibodies (ANCAs), Rheumatoid Factor (RF), Thyroid Stimulating Hormone (TSH), Free Thyroxine (T4), Antithyroglobulin Antibody Test, and Thyroid Peroxidase Antibody test (TPO). •Magnetic Resonance Images (MRI) of the primary filled areas were taken. •Biopsies of buttock lesions were taken when the patients underwent surgical removal of biopolymers.