The use of intravenous immunoglobulin in the treatment of Hashimoto's encephalopathy: case based review

Abstract

Background: Hashimoto's encephalopathy (HE) is a controversial immunological neuropsychiatric disease, with a poorly understood pathogenesis. It is characterized by symptoms of acute or subacute encephalopathy which usually occur in the presence of elevated levels of antithyroid antibodies. Even though it is also known as steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), some cases appear to be steroid-resistant. This review examined whether treatment of Hashimoto's encephalopathy with intravenous immunoglobulin (IVIG) is associated with better clinical outcomes than the standard therapy. Additionally, we presented a case of a 59-year-old man who presented with severe neurological manifestations and was successfully treated with intravenous immunoglobulin.

Methods: The online databases PubMed and EMBASE were searched.

Results: A total of 1,365 articles were identified. After the deletion of 112 duplicates, 1,253 studies were screened by evaluating the title and abstract, focusing on Hashimoto's encephalopathy cases where IVIG were used. 846 studies were excluded because they were not relevant to the topic or included pediatric population. Therefore, 407 full-text articles were assessed for eligibility. The final analysis included 14 eligible articles after 393 were excluded (irrelevant texts, not written in English, full-text not available). In the majority of the selected case-reports, IVIG was associated with a good outcome, sometimes even with dramatic improvements in patient's status.

Conclusion: In last years, intravenous immunoglobulin therapy proved its utility in Hashimoto's encephalopathy's treatment, being a well tolerated therapy associated with remarkable improvement in patient's status. Further research is still needed in order to define the optimal treatment protocol for Hashimoto's encephalopathy and to establish if intravenous immunoglobulin can also be used as a first-line therapy, alone or in combination with steroids.

Keywords: Hashimoto’s encephalopathy; alpha-enolase; anti-thyroglobulin; anti-thyroid peroxidase; autoimmune encephalopathy; intravenous immunoglobulin.

Figure 1

CT scan with no pathological findings.

Figure 2

Article selection flowchart, according to PRISMA guideline.

Figure 3

Proposed mechanism of action of IVIG in HE. IVIG employs multiple distinct mechanisms to exert its regulatory effects on various cellular and soluble constituents of the immune system. These mechanisms are not mutually exclusive and have the potential to collaboratively modulate the therapeutic outcomes. The proposed mechanism of action of IVIG in HE include: FcγR blockade leading to the potential inhibition of opsonized antigen binding, reduction in macrophage-secreted pro-inflammatory cytokines, and attenuation of granulocyte degranulation; stimulation of FcγRIIB to inhibit antibody production (84); intensified removal of pathogenic autoantibodies by saturating the FcRn or by IVIG binding to and neutralizing autoantibodies in serum (85); inhibition of T-cell proliferation and enhancing of the supressive properties of regulatory T (Treg) cells (86); prevention of membranolytic attack complex (MAC) generation and neutralization of C3a and C5a components; supressed production of pro-inflammatory cytokines, chemokines and adhesion molecules; stimulation of the production of anti-inflammatory cytokines (87); inhibition of differentiation and maturation of dendritic cells (84) (Created with BioRender.com). *B cell = B lymphocyte; M = macrophage; DC = dendritic cell; T cell = T lymphocyte; Treg = regulatory T cell; EC = endothelial cell; C = complement system.