D2.50 - When Angioedema Is Not Angioedema: Orofacial Sarcoidosis Mimicking Refractory Facial Swelling

Angioedema is characterized by transient swelling of the deep dermis and subcutaneous tissue. However, persistent or refractory facial edema should prompt consideration of alternative diagnoses, including granulomatous inflammatory disorders. Sarcoidosis is a multisystem disease that can rarely present as orofacial granulomatosis, mimicking angioedema and leading to diagnostic delay and inappropriate treatment. A 22-year-old woman presented with recurrent, painful, non-pruritic facial edema associated with swelling in extremities. Initially diagnosed with angioedema, she was treated with high-dose antihistamines, omalizumab, and prolonged courses of corticosteroids leading to exogenous Cushing's syndrome, without clinical control. The investigation for Hereditary Angioedema (HAE) was negative for C1 Inhibitor (C1-INH) deficiency (quantitative and functional), and a genetic panel for HAE including SERPING1 gene and known variants associated with HAE with normal C1-INH  in F12, PLG, ANGPT1, KNG1, MYOF and HS3ST6 genes, detected no pathogenic variants. Due to persistent otorhinolaryngological symptoms, including progressive hypoacusis, facial magnetic resonance imaging was performed, revealing infiltrative changes of the facial musculature. Subsequent biopsy of orofacial tissue demonstrated non-caseating granulomas consistent with orofacial granulomatosis. Elevated angiotensin-converting enzyme levels and hypermetabolic lesions in the thymic region on PET-CT supported the diagnosis of sarcoidosis. Treatment with methotrexate led to complete resolution of facial swelling and systemic symptoms. Orofacial sarcoidosis should be considered in the differential diagnosis of angioedema. The distinction between granulomatous infiltration and edema secondary to fluid accumulation is crucial to avoid iatrogenic morbidity due to inappropriate treatment.