X-linked hyper IgM syndrome with severe eosinophilia: a case report and review of the literature

Abstract

Background Hyper IgM syndromes (HIGMS) are a group of rare primary immunodeficiency disorders. There are limited reports about HIGMS combined with severe eosinophilia. Case presentation In this report, we described a 2-year-old boy with chronic cough and symptoms of hypoxia. Lung computed tomography (CT) scan showed that diffuse ground-glass changes and eosinophils in peripheral blood increased significantly. Subsequent tests revealed a notable decrease in serum IgG and IgA. The lymphocyte subgroup classification was basically normal. Pneumocystis jirovecii were detected from the bronchoalveolar lavage fluid (BALF) of the patient by metagenomic next-generation sequencing (mNGS). After treatments of caspofungin combined with sulfamethoxazole, intravenous immunoglobulin (IVIG) replacement and anti-inflammatory steroid, the clinical symptoms and pulmonary imaging noticeably improved. The absolute eosinophil count (AEC) also returned to normal range. X-linked hyper IgM syndrome was confirmed by gene test. Two months after the diagnosis, the patient underwent allogeneic stem cell transplantation (HSCT) and has recovered well. Conclusions Children with HIGMS are prone to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). Diffuse interstitial lung disease and hypoglobulinemia in a young child predict the diagnosis of a primary immunodeficiency (PID). mNGS has obvious advantages for obtaining etiological diagnosis of children with PIDs. Severe eosinophilia is rarely reported in this kind of PIDs. Considering literature review and the corresponding reaction to steroid, we proposed that eosinophilia in HIGMS might be related to infections. Steroid therapy can quickly relieve eosinophilia but is easy to rebound if the reduction is too fast. Once the diagnosis of HIGMS is confirmed, the earlier the HSCT, the better the prognosis.

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

“…Hence, patients classically have high IgM but low serum levels of IgG and IgA, leading to an increased risk for bacterial infections. Since the CD40/CD40L pathway also mediates co-stimulation between activated CD4 + T cells and CD40-expressing monocytes, macrophages, and dendritic cells, mutations in either CD40L (X-linked) or in CD40 (AR) also lead to opportunistic infections, notably Pjp [ 257 , 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 , 310 ]. Similarly, nuclear factor-kappa-B essential modulator ( NEMO/IKKγ ) [ 311 , 312 , 313 ], inhibitor of kappa light chain gene enhancer in B cells, alpha ( IκBα ) [ 314 ], or nuclear factor kappa-B subunit 1 ( NFKB1 ) [ 315 , 316 ] are involved in CD40/CD40L signaling, and, when mutated, interfere with CD4 + T cell/APC co-stimulation, resulting in HIGM syndrome, for which there are reports of Pjp.…”

A Retrospective Study of Clinical and Immunological Features of a Pediatric Population with Talaromyces marneffei Infection

“…Li et al reported a case with XHIGM who also had severe eosinophilia and fungal infection. After receiving anti-fungal treatment and IVIg replacement, the patient underwent allogeneic stem cell transplantation, eventually being discharged in good condition [ 28 ]. Another study by Fan et al showed that children with XHIGM were more vulnerable to respiratory infections, including T. marneffei , which in turn would help pediatricians to identify XHIGM [ 29 ].…”

Gene regulation in inborn errors of immunity: Implications for gene therapy design and efficacy

“…146 The primary line of treatment involves immunoglobulin replacement therapy and prophylactic antibiotics to ward off infections. 147 Despite treatment, the average life expectancy after diagnosis is only 25 years. 148 Allo-HSCT may be considered in extreme cases, although some studies have shown that median survival time is similar for patients past the age of 10 treated with or without allo-HSCT, likely due to prior organ damage.…”

“…Despite its rarity, more than 130 pathogenic variants of CD40LG have been reported 146 . The primary line of treatment involves immunoglobulin replacement therapy and prophylactic antibiotics to ward off infections 147 . Despite treatment, the average life expectancy after diagnosis is only 25 years 148 .…”