INTRODUCTION: Proteasome Associated Autoinflammatory Syndromes (PRAAS) are a heterogeneous group of interferonopathies caused by inherited loss of function mutation in proteasome genes. Pathogenic variants in the proteasome chaperone, PSMG2/PAC2, were described as a novel cause of this syndrome. JAK inhibitors (Baricitinib) might be a good therapeutic option.
CLINICAL CASE: 3 years-old girl. At first month, started with skin rash and swelling of fingers and toes. At 5 months was hospitalized because of prolonged fever associated with splenomegaly, livedo reticularis, and nodule at the BCG vaccine region. Laboratory evaluation: neutropenia, anemia, and elevated inflammatory parameters. Skin biopsy: neutrophilic panniculitis. Bone marrow biopsy: hemophagocytic events. She met criteria for Macrophage Activation Syndrome (MAS) and started treatment with methylprednisolone pulses and cyclosporine. At 6 months her inflammation at BCG vaccine region worsen and developed skin nodules in her right foot. Skin biopsy: positive PCR for Mycobacterium complex. Started 5-drug treatment for BCGosis and presented second MAS event. Molecular studies revealed compound heterozygous variants in PSMG2 gene, p.N225K, which was also found in her father, and deletion in exon 4, also found in the mother. IFN signature showed: High Type I IFN score PRAAS–PAC2 was assumed and search for alloSCT started, meanwhile, Baricitinib (6mg/day) was initiated a year ago, to bring the disease into remission and create a window of opportunity to prepare for HSCT. Up to date the patient continues clinically stable without BCG reactivation and normalized laboratory parameters.
CONCLUSION: We describe a patient with early-onset panniculitis and recurrent MAS as main features of an interferon dysregulation syndrome. While waiting for HSCT, JAK inhibitors seem a promising option to control inflammatory manifestations and to improve clinical and laboratory parameters, in patients with PRAAS-PAC2

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