Memory B Cell Deficiency and Disseminated Nocardiosis in a Pediatric Patient with Congenital Single Ventricle Physiology and Heart Transplantation

Abstract

IntroductionNocardiosis is infrequently described in solid organ transplant recipients. Children born with single ventricle physiology may be at increased risk due to impairments of T- and B-cell immunity from early thymectomy and other factors. We report the case of a patient born with hypoplastic left heart syndrome (HLHS), who underwent palliative surgery followed by 2 heart transplants (HT) and later contracted disseminated and incurable Nocardiosis.Case ReportA 16-year old male with HLHS underwent Norwood and Glenn palliations, followed by HT in 2008 and retransplant in 01/2021 for coronary allograft vasculopathy. Immunosuppression consisted of prednisone, tacrolimus, and mycophenolate mofetil. He presented in 07/2021 with fever and cough, found to have rhinovirus/enterovirus and multicentric pulmonary nodules on chest CT. Despite treatment for presumed bacterial pneumonia, he re-presented with persistent cough, headache, dizziness, and a seizure-like episode. Brain MRI demonstrated multifocal intracranial abscesses with ventriculitis. Chest CT showed persistent multifocal nodules. He developed hydrocephalus requiring bilateral external ventricular drains. Nocardia farcinica was detected in bronchial and cerebrospinal fluid. Immune cell profiling conducted prior to his acute illness demonstrated decreased CD31+ recent thymic emigrants and near absence of CD27+ memory B cells. Despite 6 weeks of antibiotics and IVIG, his symptoms and brain MRI findings worsened, and he ultimately passed away.SummaryDisseminated Nocardia is rare, even in solid organ recipients. In this case, T-cell immunodeficiency from neonatal thymectomy and a lack of memory B cell response likely contributed to illness severity. Immune system profiling should be considered in HT patients, especially in those with a history of infant heart surgery. The use of proper prophylaxis may prevent severe opportunistic infections. Nocardiosis is infrequently described in solid organ transplant recipients. Children born with single ventricle physiology may be at increased risk due to impairments of T- and B-cell immunity from early thymectomy and other factors. We report the case of a patient born with hypoplastic left heart syndrome (HLHS), who underwent palliative surgery followed by 2 heart transplants (HT) and later contracted disseminated and incurable Nocardiosis. A 16-year old male with HLHS underwent Norwood and Glenn palliations, followed by HT in 2008 and retransplant in 01/2021 for coronary allograft vasculopathy. Immunosuppression consisted of prednisone, tacrolimus, and mycophenolate mofetil. He presented in 07/2021 with fever and cough, found to have rhinovirus/enterovirus and multicentric pulmonary nodules on chest CT. Despite treatment for presumed bacterial pneumonia, he re-presented with persistent cough, headache, dizziness, and a seizure-like episode. Brain MRI demonstrated multifocal intracranial abscesses with ventriculitis. Chest CT showed persistent multifocal nodules. He developed hydrocephalus requiring bilateral external ventricular drains. Nocardia farcinica was detected in bronchial and cerebrospinal fluid. Immune cell profiling conducted prior to his acute illness demonstrated decreased CD31+ recent thymic emigrants and near absence of CD27+ memory B cells. Despite 6 weeks of antibiotics and IVIG, his symptoms and brain MRI findings worsened, and he ultimately passed away. Disseminated Nocardia is rare, even in solid organ recipients. In this case, T-cell immunodeficiency from neonatal thymectomy and a lack of memory B cell response likely contributed to illness severity. Immune system profiling should be considered in HT patients, especially in those with a history of infant heart surgery. The use of proper prophylaxis may prevent severe opportunistic infections.