CLINICAL, HISTOPATHOLOGICAL, IMMUNOLOGICAL AND FIBROBLAST STUDIES IN 30 PATIENTS WITH SUBCUTANEOUS INJECTIONS OF MODELANTS INCLUDING SILICONE AND MINERAL-OILS

Objective. To study patients with side effects secondary to the inject ion of modelants. Methods. We studied their clinical, serological, his topathological, radiographic, immunoregulatory and fibroblast culture features by standard methods. We studied thirty patients, 24 women, me an age: 38.2 years. Patients had received either mineral oil, guayacol , silicone or a mixture of these substances; some had received unknown material(s). Results. The mean time between the injection and the ons et of symptoms was six years (range: 0.1-24 years). All patients had s clerodermatous skin changes, subcutaneous nodules, edema and/or hyperp igmentation at the site(s) of injection(s); five individuals also had skin changes at sites remote from the injection. Thirteen patients had clinical features of an autoimmune disease. Eleven patients gave a hi story of arthralgias including four that had symmetrical non-erosive p olyarthritis. Twenty of 28 patients (71 %) had positive anti-nuclear a ntibodies. We found intracellular spontaneous production of IL-1 (inte rleukin-1) by patients' macrophages which was almost absent in normal cells (p<0.001). Silica-stimulated monocytes from patients also secret ed more IL-1 than those from normal subjects (p<0.001) in autologous m ixed lymphocyte reaction. Twelve patients had an early proliferative r esponse. At day seven, a decreased proliferative response was seen in 12/19 patients (p<0.001). Skin fibroblasts from 3/3 patients synthesiz ed 3-to-5-fold more H-3-hyaluronic acid than normal control cells (p<0 .001). Conclusions. This report confirms the association between the i njection of modelants and the development of autoimmune disease (human adjuvant disease, HAD). Our results implicate IL-1 in the amplificati on of the disease process. The similarities between primary scleroderm a and human adjuvant disease now include immunological and connective tissue data. The study of these patients may help to understand the et iopathogenesis of some autoimmune diseases.