Two cases of IgG4-related disease accompanied by many cerebral microbleeds and a review of the literature: can IgG4-related disease cause cerebral small vessel vasculitis/vasculopathy?

IgG4-related disease (IgG4-RD) is a condition of unknown cause, which involves marked tissue infiltration by IgG4-positive plasma cells into various organs throughout the body. Histopathological examinations based on biopsy examinations are essential for obtaining a definitive clinical diagnosis of IgG4-RD. However, there are only a limited number of organs from which biopsy samples can be easily obtained. Furthermore, it is impossible even for recently developed imaging techniques to directly detect abnormalities affecting small organs, such as the cerebral small vessel system. Due to these limitations, the clinical diagnosis of so-called “IgG4-related cerebral small vessel vasculitis/vasculopathy” is very difficult. In this report, two cases of IgG4-RD involving elderly patients are presented, together with their cranial magnetic resonance imaging features, especially those seen on T2* imaging. Both patients exhibited many cerebral microbleeds (CMB) on T2* imaging. I consider that it is possible to indirectly detect abnormalities of the small cerebral vessels by searching for CMB because they are caused by the failure of small cerebral vessels. Of course, the fact that many CMB were seen in both cases might be considered to be a coincidence. However, the chances of this are low because a rapid increase in the number of CMB, as was seen in case 1, and the occurrence of so many CMB, as was seen in case 2, are rare. Based on my clinical experiences and the detailed findings of the IgG4-RD cases described in this report, I present the hypothesis that “IgG4-related cerebral small vessel vasculitis/vasculopathy” exists.