Cryptococcal Meningoencephalitis in a Patient with Hyper IgM Syndrome Due to CD40 Deficiency: Case Report and Literature Review

Maram Al-Banyan,Agha M Rehan Khaliq,Farrukh Sheikh,Rand K Arnaout,Abdulhadi Alqahtani,Ashraf Al-Tarifi,Bandar Al-Saud,Hasan Al Rayes

doi:10.3844/ajidsp.2019.24.28

Abstract

Hyper-IgM syndrome (HIGM) due to CD40 deficiency is a very rare form of combined immunodeficiency with increased susceptibility to opportunistic infections. Cryptococcus is an opportunistic infection usually affecting immunocompromised individuals. This is the first report to describe a patient with HIGM due to CD40 deficiency presenting with meningoencephalitis secondary to Cryptococcus infection.

Highlights

All forms of Hyper-IgM syndrome (HIGM) constitute 0.3-2.9% of all patients with primary immune deficiencies (Yazdani et al, 2018)
HIGM due to CD40 deficiency is an autosomal recessive inheritance genetic deficit which results in the lack of CD40 expression on the surfaces of B cells and antigen-presenting (Ferrari et al, 2001) Other types of HIGM syndrome include; X-linked HIGM syndrome due to CD40 ligand (CD40L)mutation on activated T lymphocytes,intracellular deficitsintrinsic to only B cells, such as autosomal recessive mutations in activation-induced cytidine deaminase (AID) or uracilN-glycosylase (UNG) (Lougaris et al, 2005)
Patients affected with HIGM syndrome due to CD40 deficiency have a defective immunoglobulin isotype classswitching recombination (CSR) and Somatic Hyper Mutation (SHM) pathways as well as abnormality in T cell function

Summary

Introduction

All forms of HIGM constitute 0.3-2.9% of all patients with primary immune deficiencies (Yazdani et al, 2018). In previous large series for patients with HIGM due to CD40 deficiency, one third had Pneumocystis Jiroveci Pneumonia (PJP) and half had chronic diarrhea due to Cryptosporidium and devastating sclerosing cholangitis (Al-Saud et al, 2013) This susceptibility to opportunistic infections in HIGM syndrome due to CD40 deficiency is the results of functional defects in the dendritic cells of patients due to the lack of CD40-CD40L interaction between dendritic cells and activated Tcells, which leads to a defect in Tcell priming and interferon-γ secretion. Despite the initiation of anti-virals and antibiotics the patient started to become agitated and confused He was reassessed by neurology and found to have bilateral 6th nerve palsy and papilledema. CSF analysis showed clear fluid with WBC:272, neutrophils:, lymphocytes:, Eosinophils: Gram stain was negative, India ink stain showed encapsulated yeast organisms

Discussion

Conclusion