Yoshitaka Honda, Japan
Kyoto University Hospital PediatricsPresenter of 1 Presentation
A CTLA-4 HAPLOINSUFFICIENCY CASE WITH MULTIPLE BRAIN AND PULMONARY LESIONS - DILEMMAS IN MANAGEMENT
Abstract
Background and Aims
CTLA-4 haploinsufficiency is an immune dysregulation syndrome characterized by lymphoproliferation, lymphocytic infiltration in non-lymphoid organs, autoimmune cytopenias, hypogammaglobulinemia, recurrent infections. These patients are also at high risk of hematological and non-hematological malignancies.
Methods
Our case suffered from persistent Epstein-Barr virus viremia and refractory thrombocytopenia from 3-year-old, which necessitated long-term corticosteroid use, intravenous immunoglobulin, and rituximab. He is diagnosed as CTLA-4 haploinsufficiency at 5-year-old. At the age of eleven, he complained of sudden onset nausea and headache and magnetic resonance imaging of the brain revealed multiple space-occupying lesions. Whole body computed tomography revealed asymptomatic multiple pulmonary infiltrates. His medical history urged us to perform brain and lung biopsy to exclude the possibility of malignancy and lymphoproliferative disorders.
Results
Flow cytometric analysis revealed that a majority of infiltrating cells were activated CD4 T cells, supporting that these lesions are lymphocytic infiltration to brain and lung. Although almost all of the lesions disappeared after administration of high dose corticosteroid and sirolimus, existence of oligoclonal CD19-negative B cells with light chain restriction suggested the possible co-existence of lymphoproliferative disorder (LPD) or low-grade lymphoma. So, we are planning haploidentical hematopoietic cell transplantation from his mother, as there were no HLA-matched related or unrelated donors.
Conclusions
Careful assessment and management are required for multiple organ lesions observed in CTLA-4 haploinsufficiency case with long-term medical history, as these cases are at high risk of LPD or malignancies.