Abstract
Background and Clinical Significance: Granulomatous reactions are rare but clinically significant complications of aesthetic procedures involving dermal fillers, particularly in individuals with underlying immune dysregulation. These reactions present diagnostic and therapeutic challenges, especially when associated with undiagnosed or latent autoimmune diseases. This case illustrates the interaction between filler composition, immune status, and the risk of delayed inflammatory responses, underscoring the need for thorough patient evaluation and individualized management strategies. Case Presentation: A 49-year-old woman developed delayed-onset subcutaneous nodules following midface augmentation with two filler types: a monophasic, cross-linked hyaluronic acid gel (concentration 20 mg/mL, 1.0 mL per side) injected into the deep malar fat pads, and a calcium hydroxyapatite suspension (30% CaHA microspheres in a carboxymethylcellulose carrier, 0.5 mL per side) placed in the subdermal plane along the zygomatic arch. The procedure was performed in a single session using a 22 G blunt cannula, with no immediate adverse events. High-resolution ultrasound demonstrated hypoechoic inflammatory nodules without systemic symptoms. A retrospective review of her medical history revealed a latent, previously undisclosed diagnosis of granulomatosis with polyangiitis (GPA). The immune-adjuvant properties of calcium hydroxyapatite likely triggered a localized pro-inflammatory response in this predisposed patient. A conservative, staged, non-invasive therapeutic protocol-saline infiltration, intradermal polynucleotide injections, and manual lymphatic drainage-achieved complete clinical and radiological resolution without systemic immunosuppression or surgical intervention. Conclusions: This case highlights the critical importance of pre-procedural immunological assessment in aesthetic medicine. Subclinical autoimmune conditions may predispose patients to delayed granulomatous reactions after filler injections. An individualized, conservative management strategy can effectively resolve such complications while minimizing the risks associated with aggressive treatment. Greater awareness of immune-mediated responses to dermal fillers is essential to ensure patient safety and optimize clinical outcomes.