Rethinking Ormond’s Disease

Abstract

Idiopathic retroperitoneal fibrosis (RPF) is a periaortic sclerotic disease that encases adjacent retroperitoneal structures, particularly the ureters. A subset of idiopathic RPF cases can be associated with IgG4-related disease, but the frequency of this association is not clear. We selected 23 cases of idiopathic RPF and identified IgG4-related RPF cases based on the presence of IgG4+ plasma cells in the tissue, using an IgG4/IgG ratio cutoff of >40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review.We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar.IgG4-related disease accounts for a substantial percentage of patients with “idiopathic” RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic.

Retroperitoneal fibrosis – the state-of-the-art

“…Immunohistochemical and histopathological examinations of retroperitoneal tissue showed lesions specific for IgG4-RD in about half (47–59%) of patients with IRF [2, 3, 32]. …”

“…Therefore, in the case of advanced fibrotic changes, the evaluation of the ratio of IgG4+/IgG+ cells is diagnostically more useful. Other histopathological characteristics of IgG4-RD, present in the material from the retroperitoneal tissue, which help to identify IgG4-related RPF include storiform fibrosis, lymphoplasmacytic infiltration, tissue eosinophilia, and obliterative phlebitis [2]. According to some authors, the concentration of IgG4 in the serum of patients with IgG4-related RPF is significantly higher than in patients with RPF unrelated to IgG4-RD.…”

“…According to Khosroshahi et al [2] there are no significant differences in age, sex, laboratory and radiological findings among patients with IgG4-related and IgG4-unrelated RPF. However, 46–50% of cases of IgG4-related RPF show the involvement of organs located outside the retroperitoneal space; hence it is essential to distinguish these patients [2, 3].…”

“…However, 46–50% of cases of IgG4-related RPF show the involvement of organs located outside the retroperitoneal space; hence it is essential to distinguish these patients [2, 3]. Furthermore, the analysis of Koo et al [32] revealed that a group with IgG4-related RPF had a significantly higher recurrence rate compared to IRF; therefore the authors suggest the need for more aggressive immunosuppressive therapy and longer duration of maintenance treatment.…”

“…The origin of this condition may have idiopathic character (idiopathic retroperitoneal fibrosis – IRF), which covers about 2/3 of cases, or be secondary to various causes such as malignancies, drugs, infections, injuries, radiotherapy or surgery [1]. According to recent reports, approximately half of the cases of IRF can be a symptom of relatively newly described, clinically heterogeneous IgG4-related disease [2, 3]. …”