Background IgG4-related disease (IgG4-RD) is a recently recognized systemic disease of unknown etiology and prevalence [1]. Retrospective single center series have provided evidence that 13–63% of patients with idiopathic retroperitoneal fibrosis (IRPF) could be reclassified as IgG4-RD. Since immunesuppressants or B-cell targeted therapies may halt or reverse progression, early diagnosis and treatment is important to prevent terminal fibrosis.

Objectives To estimate the occurrence of IgG4 related retroperitoneal fibrosis (RPF) in Danish patients diagnosed with IRPF.

Methods The National Danish Pathology Register was searched for biopsy codes relating to retroperitoneal tissue and inflammation from 01.01.2004 through 31.12.2013. Patients below 18 years of age, secondary causes, malignancies, infections, and specimens with multinucleated giant cells or granulomas were excluded. Among 724 candidate cases 68 were identified with IRPF. Among these 25 were left out due to small tissue samples, unavailable patient files or lack of consent. Clinical, laboratory data and imagings were reviewed. Paraffin-embedded tissue blocks were retrieved from 18 pathology departments. Four sections were prepared and stained with hematoxylin-eosin, Weigerts elastin and IgG4 immunostaining. Histopathologic features suggesting an IgG4-RD background were recorded (table). Cut-off levels for IgG4 positive cells at ≥30 per HPF and IgG4: total IgG ratio at ≥40% were applied. Patients were categorized as IRPF, definite or possible IgG4-RD according to international consensus [2]. Intergroup comparisons were done using Mann-Whitney U test or Chi square test.

Results Forty three patients (29 males), median age 56 years were included among which 19 (44%) met the criteria for IgG4-RD comprising 7 with definite, 12 with possible IgG4-RD and 24 with IRPF. Biopsies were available from all participants. Extraretroperitoneal manifestations, standard laboratory measures and serum IgG4 (in 5 individuals) did not differ significantly between RPF subsets. Patients with an IgG4: total IgG ratio ≥40% had significantly more histopathologic features of IgG4-RD compared to a ratio <40% (table). Patients with ≥30 IgG4 positive cells per HPF had higher numbers of tissue eosinophils than those with lower IgG4+ cell counts.

Conclusions A total of 44% of IRPF patients was diagnosed with IgG4-RD, 16% with definite and 28% with possible IgG4-RD. This estimate may be conservative because specimens with multinucleated giant cells or granulomas were excluded. The closer association of IgG4: total IgG ratio ≥40 vs. lower ratios with histopathologic findings supports a direct pathogenic role by IgG4 bearing cells or IgG4 in IgG4 RPF.

References

1. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366 6: 539–51.

2. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25 9: 1181–92.

References

Disclosure of Interest None declared