The use of filler materials, often misnamed biopolymers, is widespread despite bans in several countries. These substances can cause type IV hypersensitivity reactions with granuloma formation and, in susceptible patients, autoimmune manifestations. The preferred term is Inflammatory Disease by Permanent Synthetic Filler Substances (EIRSP). Management of these patients should be multidisciplinary, addressing surgical, psychological, rehabilitation, and medical aspects. Anti-inflammatory treatment is essential and should always be available. General measures include avoiding heat, high-impact exercises, aesthetic treatments in areas with fillers, tight clothing, intramuscular injections in affected areas, and prolonged support on affected areas. Medical treatment varies according to the severity of lesions, from nonsteroidal anti-inflammatory drugs (NSAIDs) and systemic steroids to immunomodulators and, in severe cases, anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibodies. Regular reevaluation is necessary to monitor inflammation and antibody levels. In severe cases, hospitalization and intensive therapy may be required.