Clinical and Prognostic Significance of Serum IgG4 in Chronic Periaortitis. An Analysis of 113 Patients

Abstract

Objective: Chronic periaortitis (CP) is a rare fibro-inflammatory disorder that incorporates idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysms, and perianeurysmal retroperitoneal fibrosis. CP is included in the spectrum of IgG4-related disease. Since CP patients rarely undergo diagnostic biopsies, serum IgG4 levels are often used to classify CP as IgG4-related. However, the clinical and prognostic significance of serum IgG4 in CP is unknown. Methods: We measured serum IgG4 in active CP patients and compared the clinical characteristics, response to therapy and outcome of patients with high and normal levels. We also tested the diagnostic significance of IgG4 by comparing its levels in CP patients, healthy and disease controls (malignancies, Erdheim-Chester disease, large-, and small-vessel vasculitis). Results: We studied 113 consecutive patients with active CP. Twenty-four (21.2%) had high serum IgG4 (>135 mg/dL). The demographic, laboratory, and clinical characteristics of patients with high and normal IgG4 were similar, and so were the rates of ureteral obstruction and the disease characteristics on CT, MRI, and ¹⁸F-FDG-PET. Patients with high IgG4 only had a higher frequency of extra-retroperitoneal fibro-inflammatory lesions (p = 0.005). There were no significant differences in response to therapy and relapses between the two groups. Serum IgG4 levels did not discriminate CP from controls. Conclusions: Serum IgG4 levels are high in a minority of CP patients and do not identify specific clinical or prognostic subgroups; only a higher frequency of extra-retroperitoneal lesions is found in high-IgG4 patients. Serum IgG4 levels do not help in the differential diagnosis between CP and its mimics.

Keywords: IgG4; IgG4-related disease; fibro-inflammatory disorder; hydronephrosis; periaortitis; retroperitoneal fibrosis.

Figure 1

Serum IgG4 levels in chronic periaortitis patients and controls. In the upper figure, the plot shows serum IgG4 levels in patients with active chronic periaortitis, healthy controls, patients with aortitis (secondary to Takayasu arteritis or giant-cell arteritis), granulomatosis with polyangiitis (GPA, Wegener's) and retroperitoneal malignancies or Erdheim-Chester disease (ECD). The horizontal line indicates the upper limit of normal of serum IgG4 (135 mg/dL). In the lower figures, the receiver operating characteristic (ROC) curves show the sensitivity and specificity of serum IgG4 in discriminating chronic periaortitis patients from healthy controls (left) and aortitis patients (right).

Figure 2

CT Imaging overview of chronic periaortitis and extra-retroperitoneal lesions. (A) Sleeve thickening of the abdominal aorta (arrow) with involvement of the renal arteries; the fibro-inflammatory tissue wraps around the excretory system and determines bilateral hydronephrosis. (B) Typical aspect of “coated aorta” involvement along the descending thoracic tract: the inflammatory tissue (arrow) also expands into the paravertebral space and envelops the verterbal bodies. (C) IgG4-related chronic pancreatitis: the normal glandular structure is subverted (arrows) and a pseudonodular lesion is evident at the level of the pancreatic tail. (D) Atypical localization of retroperitoneal fibrosis: the pathological tissue encroaches into the left perirenal space (arrow) without involvement of excretory system. (E) Unusual gallbladder localization of IgG4-related disease: a bulky mass (arrow) attached to the bottom of the gallbladder with large cholecystic feeding vessels. (F) Thoracic localization: a pseudonodular lesion arises from the right pleural sheet (arrow).

Figure 3

Metabolic response to treatment assessed by FDG-PET in patients with high and normal serum IgG4 levels. Responses were evaluated as described in the text (see Methods section).

Figure 4

Relapse-free survival in patients with high and normal serum IgG4 levels. Relapse-free survival was the time from remission to relapse or last follow-up.