Digging in the DIRT Since 2018: Form, Function, and Findings of a Complex Immune Dysregulation Program

Inflammation and immune disturbance are common to the pathology of most diseases. Clinical understanding and ability to interrogate immune function lag far behind the rising number of available immune-directed therapies. Historically, diagnosis and management of patients with complex immune dysregulation is often siloed by specialty and inefficient. Building from a successful hemophagocytic lymphohistiocytosis response team, we describe our experience implementing a comprehensive, multidisciplinary dysregulated immunity response team (DIRT, colloquially) to improve the care of children with severe, recalcitrant, or otherwise complex immune dysregulation disorders. With seed support through a competitive internal mechanism, The Children's Hospital of Philadelphia Immune Dysregulation Program (IDP) commenced in 2018, graduating to an established program in 2021. With coordination by dedicated administrators and highly specialized nurse practitioners, the IDP now staffs a year-round inpatient consultation service and four outpatient clinics per month. Inpatient service is staffed by IDP infectious disease, immunology, rheumatology, hematology, or oncology specialists. Preparation for outpatient visits is tailored to individual patient needs and includes triage, prior authorization (for testing), medical record review, and determination of which IDP specialists are needed (as above and/or gastroenterology, hepatology, dermatology, neurology, and pulmonology). In Fiscal Year ’24, the IDP staffed 187 outpatient visits and 90 inpatient consultations. 36% of IDP patients traveled from >20 states outside PA/NJ and internationally. Additional clinical accomplishments include establishment of an in-house, rapid turn-around, clinical plasma cytokine panel; a weekly “office hours” external patient discussion; a widely attended weekly case teleconference; three institutional guidance documents (MIS-C, HLH, and antimicrobial prophylaxis); contributions to three international consensus guideline projects; and treatment of nine patients on single-patient investigational new drug protocols. Research accomplishments include enrollment of >325 subjects in a biobank/registry protocol and publication of eight primary manuscripts. Education/training accomplishments include establishment of an immune dysregulation elective, conducting a yearly 10+-part “Fellows Immunology Course,” hosting seven Immune Dysregulation Symposia, and receiving the first “Physician Scientist Training Program in Immune Dysregulation” award (T32AI170501). An integrated, multidisciplinary IDP is a feasible and sustainable approach to meeting the growing clinical, educational, and research challenges posed by caring for patients with complex immune dysregulation.