Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 6, 2019; 7(9): 1021-1027
Published online May 6, 2019. doi: 10.12998/wjcc.v7.i9.1021
Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values
Pierluigi Marzuillo, Stefano Guarino, Tiziana Esposito, Anna Di Sessa, Sara Immacolata Orsini, Daniela Capalbo, Emanuele Miraglia del Giudice, Angela La Manna
Pierluigi Marzuillo, Stefano Guarino, Tiziana Esposito, Anna Di Sessa, Sara Immacolata Orsini, Daniela Capalbo, Emanuele Miraglia del Giudice, Angela La Manna, Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli 80138, Italy
Author contributions: Marzuillo P, La Manna A, and Guarino S contributed to research idea and study design; Esposito T, Di Sessa A, and Orsini SI contributed to data acquisition; Marzuillo P and Miraglia del Giudice E contributed to data analysis/interpretation; Marzuillo P, Di Sessa A, and Capalbo D contributed to statistical analysis; Miraglia del Giudice E, La Manna A , and Marzuillo P contributed to supervision or mentorship; Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Institutional review board statement: Our Institutional Review Board approved the study.
Conflict-of-interest statement: Nothing to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Pierluigi Marzuillo, MD, PhD, Doctor, Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, Naples 80138, Italy. pierluigi.marzuillo@gmail.com
Telephone: +39-81-5665465 Fax: +39-81-5665427
Received: February 25, 2019
Peer-review started: February 26, 2019
First decision: March 10, 2019
Revised: March 20, 2019
Accepted: April 9, 2019
Article in press: April 9, 2019
Published online: May 6, 2019
Abstract
BACKGROUND

In paediatric patients with complicated nephrotic syndrome (NS), rituximab (RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G (IgG) levels.

AIM

To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.

METHODS

We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation (SD)].

RESULTS

We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients (55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two “starting doses” experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose.

CONCLUSION

RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.

Keywords: Nephrotic syndrome, Rituximab, IgG hypogammaglobulinemia, Immunoglobulin

Core tip: In paediatric patients with complicated nephrotic syndrome (NS), rituximab (RTX) administration can induce persistent immunoglobulin G (IgG) hypogammaglobulinemia among subjects showing low basal IgG levels. Our case series shows that RTX can induce IgG hypogammaglobulinemia also in patients with pre-RTX IgG normal values and that persisting IgG hypogammaglobulinemia could be dose-dependent. When evaluating a patient with complicated NS and post-RTX IgG hypogammaglobulinemia, IgG supplementation may not be needed because, to date, no severe infections have been detected and the possibility of adverse events related to IgG supplementation exists.