Background: Coatomer protein subunit alpha (COPA) syndrome, first described in 2015 is a autoinflammatory syndromic illness characterised by an arthritis, pulmonary infiltrates, and glomerulonephritis. EULAR in collaboration with ACR produced a guideline in 2021 on interferonopathies however COPA syndrome was not described within the guideline. Due to its rarity, time to diagnosis remains prolonged with limited treatment options.

Objectives: We performed a systematic literature review for case reports of COPA syndrome to further understand the patterns in phenotype, association with auto-antibodies and treatment options.

Methods: We performed a MEDLINE, Embase and Cochrane library search from inception till 20 ^th September 2025 of case reports with confirmed cases of COPA syndrome with describing data on presentations, management options and outcomes. A further search in ClinVar, and Online Mendelian Inheritance in Man (OMIM) was performed.

Results: There were 108 case reports of COPA syndrome A case series of 3 patients were excluded from the analysis as the data were not extractable. We reported on 105 cases. The average age at presentation was 10.15 years. 49 were female and the most frequent manifestation of the disease was pulmonary infiltrates. 63 had interstitial lung disease with an NSIP predominant pattern (99%), followed by ground glass changes in 37 patients, cystic lung lesions 24 patients, diffuse alveolar haemorrhage in 23 patients. Musculoskeletal involvement was the second commonest organ system affected with 56 patients having a polyarthritis. 19 patients in the total cohort had renal manifestations. Cutaneous and neurological manifestations were rare. Cystic lung lesions were seen more frequently in the adult population (29% vs 58%), with no rise in immunoglobulins amongst the adult populations. Autoantibodies were present with ANA (N=28), Rheumatoid Factor (N=27), Anti-citrullinated antibody (CCP) (N=18), ANCA (N=28). A combination of csDMARD’s and TNF inhibitors were used pre-diagnosis and following diagnosis, 11 patients received a lung transplant for their interstitial lung disease. 20 patients received JAK inhibitors as part of their management of which 10 patients received baricitinib. Death was described in 3 patients.

Conclusions: Initially described in 2015 as a paediatric pathology, this rare disease remains a differential when considering both interstitial lung disease and a polyarthritis despite positive auto-antibodies. It has been seen in both adult and paediatric populations. Cystic lung lesions and interstitial lung disease dominant what has been reported in the literature. Baricitinib remains viable option to achieve disease control.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.