D1.255 - Is it Angioedema? Unmasking a complete Melkersson-Rosenthal Syndrome

Introduction: Differentiating true angioedema (AE) from pseudoangioedema, such as granulomatous diseases, remains a challenge, particularly in patients without urticaria. Melkersson-Rosenthal Syndrome (MRS) is a rare neuro-mucocutaneous granulomatous disorder defined by a triad: recurrent facial and lip swelling (cheilitis granulomatosa), episodes of facial palsy, and fissured tongue. Diagnosing this syndrome may be challenging, especially since the complete triad rarely occurs simultaneously, with symptoms often presenting asynchronously over long periods.

Case Description: A 49-year-old female presented to the Immunoallergology Department in July 2020 with a one-year history of recurrent, non-pruritic lip swelling, without associated urticaria. She had no history of atopy or family history of AE, nor did she recognize any food, drug or other triggers. Her only regular medication was valaciclovir 500 mg daily for recurrent herpes labialis. The initial diagnostic workup included skin prick tests for food and aeroallergens (negative), routine laboratory tests and complement studies within normal ranges, as well as negative autoimmune screening and infectious serologies (HIV, hepatitis and others). Initial management included on-demand antihistamines and systemic corticosteroids, followed by escalation to maintenance bilastine (20 mg twice daily), with no reduction in episode frequency or severity. Over 5 years of poor disease control, episodes became more frequent and the edema evolved from soft to persistent and indurated. In May 2025 an incisional lip biopsy was requested and histology revealed mast and lymphoplasmohistiocytic cell infiltration with perivascular granulomas, consistent with cheilitis granulomatosa. Subsequently, a new detailed physical examination and review of systems revealed a fissured tongue and history of two prior episodes of "idiopathic" facial palsy (ages 27 and 44). The patient was diagnosed with MRS (complete triad) and started dapsone (100mg/day), currently with clinical improvement.

Conclusion: This case highlights the importance of a thorough etiological investigation in patients with suspected AE, particularly those with atypical or treatment-refractory symptoms. The complete triad of MRS is uncommon (8-25% of cases) and symptoms often appear asynchronously, decades apart. Clinicians must maintain a high suspicion of other conditions as differential diagnosis to AE, to avoid delayed diagnosis and ensure appropriate treatment.