B DISCERNING: ROLE OF RITUXIMAB IN INTERFERON GAMMA AUTOANTIBODY DISEASE

Abstract

<h3>Introduction</h3> Adult-onset immunodeficiency with anti-interferon gamma autoantibodies can lead to disseminated infections by opportunistic pathogens. This case describes interferon gamma autoantibodies responsible for treatment resistant disseminated mycobacterium avium (MAC) infection. <h3>Case Description</h3> A 52 year-old man originally from Laos was seen as an outpatient consult for concern for immunodeficiency. He originally presented with weight loss and fatigue, and CT chest showed a spiculated mass with lymphadenopathy. Lymph node biopsy demonstrated MAC, and PET scan suggested multi-organ disease. He failed to improve on standard antimicrobial therapy, requiring prolonged hospitalization. Family history was significant for parental consanguinity and a sister with severe MAC infection. Our differential diagnosis included Mendelian susceptibility to mycobacterial disease (MSMD) and acquired interferon-gamma autoantibodies. Genetic testing with the Invitae Primary Immunodeficiency panel was unrevealing, and testing for clinically significant interferon gamma autoantibodies was positive. Due to further clinical deterioration, treatment with rituximab was initiated. His symptoms improved after four weekly infusions with complete depletion of B cells. Despite clinical improvement, he was re-admitted for AKI and hypercalcemia resistant to standard management. His hypercalcemia was ultimately attributed to immune reconstitution inflammatory syndrome (IRIS) due to granulomatous MAC formations. <h3>Discussion</h3> Severe MAC infections are rare and should bring to mind both Mendelian susceptibility to mycobacterial disease and acquired autoantibodies directed against interferon gamma. Rituximab therapy should be considered for patients with auto-antibodies who do not respond to antimicrobial therapy. A potential consequence of such therapy is hypercalcemia secondary to immune reconstitution inflammatory syndrome.