CHOOSE YOUR OWN ADVENTURE: AUTOINFLAMMATORY DISEASE, IMMUNODEFICIENCY, AND HIRSCHSPRUNG'S, OH MY!

Abstract

<h3>Introduction</h3> Overlapping manifestations of immune dysregulation and immunodeficiency can create diagnostic challenges. A rapidly expanding array of genetic testing provides additional information in understanding disease manifestation in medically complex patients. Here we present the case of a pediatric patient with recurrent infections, drug reaction and a <i>CARD11</i> variant of uncertain significance (VUS). <h3>Case Description</h3> The patient is a five-year old male with a history of multiple prior gastrointestinal infections in the setting of Hirschsprung's disease. After receiving cephalexin for enterocolitis, he developed a malar facial rash and fatigue which was concerning for drug-induced lupus. Laboratory evaluation showed normal complete blood count, quantitative immunoglobulins, total complement (CH50), and quantitative lymphocytes. He had positive antinuclear, double stranded DNA, ribonucleoprotein, Smith and antichromatin antibodies. Additionally, work-up revealed <i>CARD11</i> exon duplication of unknown significance. Symptoms of lupus improved with medication discontinuation. Ultimately, the patient's infectious history was attributed to his primary Hirschsprung's diagnosis though the impact of the <i>CARD11</i> VUS is unclear. <h3>Discussion</h3> We present a case in which work-up for immunodeficiency in the setting of Hirschsprung's disease and suspected drug-induced lupus led to identification of a <i>CARD11</i> variant. Mutations in <i>CARD11</i> have been implicated in immunodeficiency, atopy and B cell expansion due to signaling dysregulation. Hypomorphic mutations in <i>CARD11</i> are associated with a variety of clinical phenotypes and clinical symptoms that have not been fully elucidated. Although currently recognized as a VUS, this case highlights the need for a high index of suspicion and genetic testing to help guide clinical practice.