(430) Infantile Autoimmune Vasculitis With Multisystem Organ Involvement

Introduction: Mutations in TNFAIP3 have been linked to a variety of autoimmune diseases. This patient represents one of the youngest and most severe presentations of TNFAIP3-associated autoimmune vasculitis as documented in the literature.

Description: A 33-day old full term female presented with vomiting and diarrhea since birth, weight loss (13% below birth weight), acute hypoxic and hypercarbic respiratory failure, methemoglobinemia and severe non-anion gap metabolic acidosis. Patient was additionally found to be in status epilepticus. Infectious workup revealed a viral respiratory illness. After initiating enteral feeds, the patient developed severe protein losing enteropathy with bilateral transudative pleural effusions, a lacy erythematous rash and multiple deep vein thromboses, including a 5mm thrombus in the right atrium, despite systemic anticoagulation. Inflammatory markers were notable for an elevated ferritin, fibrinogen, ESR and CRP. A workup for immunodeficiency revealed low IgG, elevated IL-6 and elevated IL-2 alpha receptor levels. Due to the severe systemic inflammation of unclear etiology and clinical concern for an inflammatory bowel disease (IBD)-like syndrome, InVitae Primary Immunodeficiency Panel testing was sent. This panel revealed a unifying diagnosis of a pathogenic mutation in the TNFAIP3 gene, associated with haploinsufficiency of NFKB regulatory protein A20, consistent with a vasculitis such as Familial Bechet’s. For this patient, the autoimmune vasculitis impacted both large and small veins, CNS, skin and GI tracts. After diagnosis the patient was started on high dose steroids and Infliximab. The patient showed rapid improvement in inflammatory markers, resolution of effusions, improvement in hypoalbuminemia and was able to tolerate enteral feeds and gain weight.

Discussion: The pathogenic variant of TNFAIP3 has been documented to have variable penetrance as well as a variable clinical presentation. The most common presentation of this mutation is oral and skin ulcers, but can include GI findings (bowel perforation, very early onset IBD), joint findings (arthritis), ocular findings (uveitis, retinal vasculitis), hypercoagulable state, pericardial effusions, and CNS vasculitis.