Inborn Error of Immunity Presenting with Salmonella Pericarditis and Pericardial Effusion

Abstract

Salmonella infections typically occur in disorders of innate immunity with impairment in phagocyte function and/or impaired signaling in the IL-12/interferon (IFN)-gamma axis. Pericarditis/pericardial effusion has previously been reported as a rare complication of Salmonella infection.An 8-year-old, previously healthy, fully immunized Hispanic female presented with 4 days of fever and 5 days of pain in her chest, abdomen, and left shoulder. Her medical and family history was unremarkable. Chest radiograph revealed cardiomegaly, and a transthoracic echocardiogram identified a large pericardial effusion. Labs showed leukocytosis (15 K/uL), neutrophilia (ANC 12.77 K/uL), elevated CRP (287 mg/dL), and elevated BNP (607 pg/mL). Exam showed mild distress, gallop on cardiac auscultation, diminished left breath sounds, cool extremities, and 1+ peripheral pulses. She underwent pericardiocentesis, and the fluid culture was positive for Salmonella alachua. She was treated with IV ceftriaxone for 8 days, then transitioned to trimethoprim/sulfamethoxazole (TMP/SMX) to complete a 30-day total antibiotic course.Inpatient immunologic evaluation revealed T cell lymphopenia (TCL) with decreased naïve CD4+ and CD8+ T cells. Increased CD4+ and CD8+ effector memory T cells (Tem) were also observed, along with increased CD8+ TEMRA, and certain subsets of CD4+/CD8+ central memory T cells lacking CD62L. HIV testing and neutrophil oxidative burst were negative. Given her significant T cell lymphopenia, TMP/SMX prophylaxis was continued after the treatment course, and fluconazole prophylaxis was initiated due to endemic coccidiomycosis.A targeted 429-gene panel for inborn errors of immunity revealed a heterozygous missense variant of uncertain significance in PIK3CD, = c.1013G>A, p.Arg338Gln. This variant is not in gnomAD for Hispanics and is present in 0.0009% of non-Finnish Europeans. Gain-of-function (GoF) PIK3CD mutations cause a combined immunodeficiency, with increased risk of infection from encapsulated organisms, such as salmonella. However, the patient’s immunophenotype is not consistent with GoF PIK3CD mutation. She had normal transitional B cells, lack of increased senescent T cells, and absence of lymphoproliferation.TCL is likely an immunologic risk factor for Salmonella pericarditis with pericardial effusion. Though the PI3CKD variant does not appear to be pathogenic, additional functional testing for this variant is in progress.