AB0030 EXPANDING HORIZONS: MONOGENIC AUTOINFLAMMATORY DISORDERS IN A NORTH INDIAN TERTIARY RHEUMATOLOGY CARE CENTRE
Authors: R. Chatterjee, L. Minikumari Rahulan, A. Balakrishnan, F. Umam, F. Hasan, V. Bhatia, S. Phadke, U. Poddar, D. P. Misra, A. Lawrence, A. Aggarwal
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Autoinflammatory diseases manifest as recurrent fever and sterile inflammation impacting multiple organs. In rheumatology clinics, polygenic conditions like Systemic onset JIA, Adult-onset Still's disease and Behcet's disease prevail, whereas monogenic variants are rare, often leading to diagnostic delays. Early recognition of phenotypic traits and genetic testing are pivotal in guiding treatment, utilizing biologics, small molecules, or allogenic stem cell transplant. <h3>Objectives:</h3> To describe the clinical spectrum, genetic etiology and outcomes of patients with autoinflammatory diseases. <h3>Methods:</h3> A retrospective analysis encompassing patients from our clinic from 2013-2023 was undertaken. We scrutinized patients clinically diagnosed with autoinflammatory syndromes. Clinical profiles and available genetic test results were collated from case records and electronic databases. <h3>Results:</h3> Among the 47 suspected cases of autoinflammatory diseases, 27 underwent genetic testing, confirming diagnosis in 21 instances. Notably one suspected Blau syndrome case tested negative for NOD2 mutation. For the 26 cases displaying the characteristic clinical phenotype, the median age of presentation was 168 months (72-213), with onset typically occurring around a median age of 39 months (6-174). The male to female ratio was 1.36:1. There was median delay in diagnosis of 48 months (24-115) and patients had a median follow up duration of 16.5 (5.5-46.5) months. Predominant manifestations included fever (n=15, 57.6%), mucocutaneous symptoms (n=15, 57.6%), musculoskeletal symptoms (n=10, 38.4%), cytopenia (n=6,23.07%), vasculitis (n=5,19.2%) and hearing loss (n=3, 11.5%), alongside diverse systemic manifestations. A history of infections was present in 5 patients (19.2%). Family history of consanguinity was present in 1 patient (3.8%) while similar diseases or unexplained early deaths in relatives was there in 7 patients (26.9%). Diagnoses spanned various conditions like Hyper IgD syndrome, Muckle Wells syndrome, Neonatal onset multisystem inflammatory disease (NOMID), Histiocytosis-Lymphadenopathy plus syndrome (H syndrome) and deficiency of adenosine deaminase 2 (DADA2) among others, highlighting the spectrum of disorders encountered (Table 1). Regarding treatment response, 18 patients (69.2%) had good or partial response to therapy while 6 patients (23.07%) were lost to follow up. Majority of patients (n=22, 84.61%) had received some form of immunosuppression. One patient with STING associated vasculopathy of infancy (SAVI) who had excellent initial treatment response to Tofacitinib had weaning of the effect later, while another patient with DADA2 and severe cytopenia succumbed to her illness. <h3>Conclusion:</h3> The spectrum of monogenic autoinflammatory syndromes continues to broaden. Early identification, facilitated by vigilant observation and interdepartmental collaboration, can significantly enhance treatment efficacy and enable informed genetic counselling. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>