PO:36:250 | Eosinophilic granulomatosis with polyangiitis associated to Alpha-1 Antitrypsin Deficiency: a land still unexplored

Maria Grazia Malandra¹, Vacchi Caterina¹, Santoro Filippo¹, Cassone Giulia¹, Martina Orlandi¹, Stefania Cerri¹, Dilia Giuggioli¹ | ¹Università di Modena - Reggio Emilia, S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ²S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ³Università di Modena e Reggio Emilia, S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ⁴S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ⁵Università di Modena e Reggio Emilia, S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ⁶Università di Modena e Reggio Emilia, S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy; ⁷Università di Modena e Reggio Emilia, S.C. Reumatologia Azienda Ospedaliera Universitaria Policlinico di Modena Modena, Italy

Background. Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a small-vessel vasculitis often associated with ANCA auto-antibodies. Alpha-1 Antitrypsin Deficiency (AATD) is an autosomal hereditary condition involving mainly lungs and liver, caused by mutations on SERPINA 1 gene. AAT is a serine proteinase inhibitor whose molecular targets include neutrophil elastases and proteinase-3 (PR-3). The normal variant is conventionally marked as *M allele while *S and *Z are the two most common variants encoding for a deficient enzyme. Some studies have reported an association between Z allele and ANCA-associated vasculitis (AAV) and both conditions can share many signs and symptoms. Here we describe the case of a patient with AATD and a later diagnosis of EGPA. Case report. A 60-year-old woman was referred to our center in March after being admitted for recent onset of myalgias and cough. Her medical history revealed a heavy smoking habit, dyslipidemia, and bronchial asthma. Blood tests showed leukocytosis (WBC 18.820/mmc), eosinophilia (E 11.000/mmc), elevated inflammation markers (CRP 3.9 mg/dl), and high CK (1374 U/ml). Chest X-ray showed an opacity in the middle lobe. Autoimmunity revealed the presence of high titer MPO-ANCA (107.0 UI/ml). A deeply thorough rheumatological anamnesis revealed a history of pansinusitis complicated by nasal polyps, sensory bilateral hearing loss, recent onset of joint swelling, newly-appeared paresthesia in her upper and lower extremities with mononeuritis multiplex in EMG. An ENT specialist confirmed chronic rhinitis in EGPA. PFTs revealed a reversible airflow obstruction. Considering the clinical and laboratory data, a diagnosis of EGPA was confirmed. We initiated treatment with high-dose glucocorticoids and rituximab, followed by mepolizumab (300 mg every four weeks). In June 2024 the patient was evaluated in a multidisciplinary setting attended by rheumatologists and pneumologists, reporting significant clinical improvement. During her assessment, a pneumologist pointed out that years before the same patient had been evaluated for a deficit in the alpha1 region in serum protein electrophoresis and was diagnosed with AATD - she was lost to follow-up afterwards. Given present circumstances, a genetic test for AATD was performed revealing AATD with a rare heterozygous genetic display – Pi*S/Q0Clayton. Since there were no signs of emphysema or liver damage, there was no need to start replacement therapy. The patient stays in remission to this day. Discussion and

Conclusions. This is one of the first instances recording the simultaneous presence of EGPA and AATD, the very first involving such a rare phenotype. Increased awareness about this association could be acquired by measuring AAT values in all patients with EGPA and deepening with genetic testing if necessary. The search for this deficiency may have clinical and therapeutic implications, especially if the need for replacement therapy is considered.