Clinical features and treatment of activated PI3K-delta syndrome in Peruvian children: A case series

Abstract

IntroductionActivated phosphoinositide 3-kinase δ (PI3Kδ) syndrome (APDS) is an inborn error of immunity (IEI) caused by a gain-of-function mutation in the PIK3CD gene. It is characterized by recurrent respiratory infections, chronic herpes infections, lymphoproliferation, mucosal lymphoid hyperplasia, enteropathy and immune dysregulation. This condition can be misdiagnosed with other diseases, such as lymphoma or other IEI. Additionally, limited knowledge of APDS in physicians could generate delay in diagnosis, treatment and lead to worse outcomes, especially in developing countries. This study aimed to describe the clinical features and treatment of APDS in Peruvian children evaluated in two centers. MethodsWe retrospectively analyzed data from eight patients with APDS evaluated in the two main Peruvian clinical immunology centers. Demographics, clinical features, laboratory analysis, and treatment data were included. ResultsAll patients were female. At the onset of symptoms and diagnosis, the mean age was 1.4 (SD: 0.98) and 6 (SD: 2.1) years, respectively. The mean delay in diagnosis was 4.5 (SD: 2.7) years. No consanguinity was reported, and only one patient had a family history of IEI. The mortality rate was 25% (2 patients). The main clinical manifestations were lymphadenopathy and hepatomegaly (100%), chronic diarrhea and recurrent pneumonia (87.5%), and splenomegaly (62.5%). All the patients had E1021K mutation. Seven patients (87.5%) had elevated IgG and 50% had elevated IgM. Regarding treatment, all the patients received intravenous immunoglobulin (IVIG), 50% were treated with everolimus and only one patient received hematopoietic stem cell transplantation. ConclusionLymphadenopathy, hepatosplenomegaly, chronic diarrhea, pneumonia, and IVIG treatment were the main features. Our cohort had limited treatment options with calcineurin inhibitors and transplantation and laboratory testing such as lymphocyte population and functional antibody tests. Although genetic testing was done on all the patients, it was supported by international collaboration. Therefore, further studies are needed to evaluate the diagnosis and management impact on patients with APDS in our setting.