Update on IgG4-related periaortitis/retroperitoneal fibrosis and periarteritis -recent clinical, diagnostic and therapeutic advances.

Background: IgG4-related disease (IgG4-RD) is a systemic, chronic immune-mediated inflammatory disorder that, similar to sarcoidosis, can affect various organs and tissues. IgG4-related periaortitis (PAo)/retroperitoneal fibrosis (RPF) is among the five major manifestations of IgG4-RD. Despite introduction of the ACR and EULAR classification criteria for IgG4-RD in 2019, diagnosing IgG4-related PAo/RPF and periarteritis (PA) remains challenging because obtaining biopsies from these lesions is difficult. Additionally, while glucocorticoids are highly effective in treating IgG4-RD, managing aortic or arterial lesions poses unique challenges.

Objectives: This brief review discusses the utility of Japanese organ-specific diagnostic criteria for IgG4-related PAo/RPF and PA, along with recent advances in treatment strategies including management of organ-specific issues related to these lesions.

Methods: First, we analyzed 99 patients with IgG4-related PAo/RPF and PA based on expert diagnoses to propose organ-specific diagnostic criteria. Next, we retrospectively analyzed an additional 110 patients with IgG4-related PAo/RPF and PA, as well as 73 mimickers with clinical features requiring differentiation from true IgG4-RD to validate the proposed criteria.

Results: Histopathological specimens were obtained from only 33 patients (20 periaortic, 5 coronary arteries, 4 iliac arteries, 1 mesenteric artery, and 5 retroperitoneal lesions not involving arteries). Among these, 71.4 % showed storiform fibrosis, and 71.4 % displayed obliterative phlebitis. The mean number of IgG4-positive plasma cells exceeded 10 per high-power field in all specimens, and the IgG4/IgG-positive cell ratio exceeded 40 % in 32 specimens (91.4 %). Radiographic findings were essential for diagnosing IgG4-related PAo/RPF and PA, supported by elevated serum IgG4 levels and the presence of characteristic involvement of other organs affected by IgG4-RD. Validation analysis confirmed that incorporating "imaging findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-Pao/PA/RPF lesions" improved sensitivity from 68.4 % to 77.2 %, with only a minimal reduction in specificity (from 97.4 % to 94.7 %).

Conclusions: Diagnosing IgG4-related PAo/RPF and PA remains challenging even when using the latest diagnostic or classification criteria, compared to diagnosing IgG4-RD involving other major organs, such as lacrimal and salivary glands, pancreas, and kidneys. In addition, when treating patients with IgG4-related PAo/RPF and PA, organ-specific factors must be considered when developing treatment strategies.